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Palliative care in patients with end-stage renal disease: a meta synthesis.

1. Introduction

2. materials and methods, 2.1. design, 2.2. search methods, 2.3. search strategy, 2.4. search outcomes, 2.5. quality appraisal, 2.6. data abstraction, 2.7. synthesis.

3.1. Struggling to Face the Disease

3.1.1. negative feelings associated with the disease, 3.1.2. dialysis to stay alive, 3.2. experience deterioration, 3.2.1. changes in functional status, 3.2.2. changes in emotional status, 3.2.3. changes in social status, 3.3. overcoming the challenges of dialysis, 3.3.1. facing difficulties in treatment decisions, 3.3.2. lack of control of daily life, 3.3.3. financial strains, 3.4. leading to a positive outlook, 3.4.1. increasing attachment to god, 3.4.2. building relationships with healthcare professionals, 3.4.3. accepting the present quality of life, 3.4.4. predicting the future, 3.5. preparing for the end of life, 3.5.1. information about prognosis, 3.5.2. awareness of mortality, 3.5.3. talking about acp issues, 4. discussion, 4.1. implications for practice, 4.2. strength and limitations, 5. conclusions, author contributions, institutional review board statement, informed consent statement, data availability statement, conflicts of interest, ethical considerations.

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Imamah, N.F.; Lin, H.-R. Palliative Care in Patients with End-Stage Renal Disease: A Meta Synthesis. Int. J. Environ. Res. Public Health 2021 , 18 , 10651. https://doi.org/10.3390/ijerph182010651

Imamah NF, Lin H-R. Palliative Care in Patients with End-Stage Renal Disease: A Meta Synthesis. International Journal of Environmental Research and Public Health . 2021; 18(20):10651. https://doi.org/10.3390/ijerph182010651

Imamah, Nur Fithriyanti, and Hung-Ru Lin. 2021. "Palliative Care in Patients with End-Stage Renal Disease: A Meta Synthesis" International Journal of Environmental Research and Public Health 18, no. 20: 10651. https://doi.org/10.3390/ijerph182010651

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• Original research article
• Open access
• Published: 10 September 2024

Shared decision-making in end-of-life care for end-stage renal disease patients: nephrologists’ views and attitudes

• Wassiem Bassam Abu Hatoum 1 , 2 &
• Daniel Sperling   ORCID: orcid.org/0000-0002-4371-7736 1  

Israel Journal of Health Policy Research volume  13 , Article number:  45 ( 2024 ) Cite this article

Metrics details

The term end-stage renal disease (ESRD) refers to the final stage of chronic kidney disease. Not all ESRD patients are suitable for dialysis treatment, which despite its advantages, is not without risks. Shared nephrologist-patient decision-making could be beneficial at this stage, yet little is known about such practices in Israel. This study aimed at examining the practice of shared decision-making (SDM) between nephrologists and ESRD patients in Israel, while exploring related conflicts, ethical dilemmas, and considerations.

The descriptive-quantitative approach applied in this study included a validated questionnaire for nephrologists, based on Emanual and Emanual (1992). The survey, which was distributed via social-media platforms and snowball sampling, was completed by 169 nephrologists. Data analysis included t-tests for independent samples, f-tests for analysis of variance, and t-tests and f-tests for independence. Descriptive analysis examined attitudes towards SDM in end-of-life care for ESRD patients.

The findings show that the research sample did not include nephrologists who typically act according to the paternalistic decision-making style. Rather, 53% of the respondents were found to act in line with the informative decision-making style, while 47% act according to the interpretive decision-making style. Almost 70% of all respondents reported their discussing quality-of-life with patients; 63.4% provide prognostic assessments; 61.5% inquire about the patient’s desired place of death; 58.6% ask about advance directives or power-of-attorney; and 57.4% inquire about cultural and religious beliefs in end-of-life treatment. Additionally, informative nephrologists tend to promote the patients’ autonomy over their health ( P  < 0.001); they are also in favor of conservative treatment, compared to paternalistic and interpretive nephrologists, and use less invasive methods than other nephrologists ( P  = 0.02).

Conclusions

Nephrologists in Israel only partially pursue an SDM model, which has the potential to improve quality-of-care for ESRD patients and their families. SDM programs should be developed and implemented for increasing such practices among nephrologists, thereby expanding the possibilities for providing conservative care at end-of-life.

Introduction

The term end-stage renal disease (ESRD) refers to the final stage of chronic kidney disease [ 1 ]– including transplantation, hemodialysis, and peritoneal dialysis [ 2 ]. Yet dialysis is not simple to endure, especially as most patients are elderly and have complex medical backgrounds [ 3 ]. Dialysis may also have undesirable psychosocial outcomes, and its aims for a specific patient may not always be clear [ 4 ]. As such, not all patients are suitable for dialysis, and those who do embark on this treatment may become too frail to continue [ 5 ]. In such cases, more conservative treatment may be considered a better alternative, such as pain control, psychological and emotional therapy [ 6 ], and even palliative care (PC) – especially when the outcomes of prolonged survival do not seem beneficial [ 4 , 7 ]. In light of this complexity, guidelines have been issued in the USA for treating ESRD patients, including the addressing of issues such as futile dialysis, withdrawing dialysis, and PC [ 8 , 9 , 10 ].

These guidelines also highlight the importance of shared nephrologist-patient decision-making – a process that would help nephrologists deal with related dilemmas. In shared decision-making (SDM), both the healthcare professional and the patient play a role and make decisions regarding the course of treatment that will be pursued [ 11 ]. Moreover, the approach of inter-professional SDM entails collaborations between a number of healthcare professionals and the patients themselves, with the aim of making optimal decisions that also consider the patient’s personal preferences [ 12 ]. Encouraging such collaborations between multi-disciplinary teams, while allocating team tasks, could play a pivotal role in integrating and maintaining SDM as a routine medical practice [ 13 ].

According to the American Renal Physicians Association, SDM is especially desirable when caring for ESRD patients [ 14 ]. Yet little is known about SDM and end-of-life (EOL) care among nephrologists in Israel. Since related guidelines in Israel do not exist, this study is of great importance – especially as physicians have been found to make treatment-related decisions based solely on the patient’s age and comorbidity [ 15 ]. The aim of this study, therefore, was to examine the degree to which SDM is applied when treating ESRD patients in Israel, while exploring ethical and other dilemmas that nephrologists face when providing such patients with EOL care.

Literature review

Shared decision-making (sdm).

SDM enables clinicians and patients to jointly choose the treatment path, after assessing the options and considering the patient’s preferences [ 16 , 17 ]. SDM strives to prioritize the patient [ 12 ], by addressing their preferences, improving their knowledge, and enhancing clinician-patient communications [ 17 ]. Yet in Israel, nephrologists lack practical, research-based guidelines for conducting SDM – in EOL care in general, and in ESRD patients in particular. Moreover, these physicians do not undergo adequate SDM training, nor do they have sufficient access to the relevant research literature [ 17 ]. Such guidelines are especially important as nephrologists may suffer emotional burden following their decision-making, for example when a patient does not fare well with dialysis, yet the alternative is imminent death [ 18 , 19 ].

While SDM has become a common clinical practice in nephrology care in the USA [ 20 , 21 ], and a health-policy priority in Europe [ 16 ], it has not been broadly or officially introduced into nephrology units in Israel. More generally, SDM is not frequently reported in Israel. First, patients tend to rely on their physicians to make the right decisions for them; alternatively, physicians may implement persuasion tactics, to encourage the patient to agree with the course of action that they have suggested. Moreover, physicians lack training in SDM, especially during their medical preparation. As a result, they may not adequately understand or interpret the risks and benefits that are characteristic of SDM [ 22 ].

Barriers in caring for ESRD patients

In the USA, variations can be seen in decision-making practices among nephrologists when providing EOL care [ 7 , 8 , 23 ]. Medical directors report that they respect the requests of their competent patients to withhold or withdraw from dialysis; 17% agree that they would start or continue dialysis in permanently-unconscious patients; and 32% would do so for patients with advanced dementia or without advance medical directives [ 24 ]. Nephrologists also claim that their dialysis-related decisions are most influenced by their patients’ preferences and by the clinical urgency, followed by input from family members [ 19 , 25 , 26 ]. Finally, older nephrologists (≥ 65 years) are more likely to recommend dialysis rather than conservative care (CC) compared to their younger colleagues [ 27 ].

Studies conducted in the USA found that most dialysis professionals conduct EOL discussions with patients and feel well prepared for making related decisions; they also prefer to follow a decision-making model, and tend to provide recommendations after presenting the patient with various treatment options [ 15 ]. Most nephrologists report that they feel comfortable with providing EOL care for patients who have advanced chronic kidney disease [ 19 , 26 , 28 , 29 ]; yet they do face a range of challenges when discussing EOL with their patients, such as the families’ lack of cooperation and their own fear of eliminating hope. Additional barriers stem from inadequate palliative or hospice care options, and from the family’s reluctance to discuss EOL care [ 19 , 28 ]. Other reasons may include the patient’s refusal to participate in the decision-making process, difficulty understanding the treatment options, and lack of patient motivation. Decisions may be made quickly, without weighing all of the options that are available to the patient. In some cases, the clinician’s decision-making style inhibits SDM – especially when lacking SDM-specific training or supporting services [ 30 ].

SDM may not always be applied in cases where the patients explicitly state their desire not to pursue dialysis, yet the physicians disagree with their choice – especially if they are not certain of their patients’ competency to make such decisions. From the patients’ point-of-view, feelings of frustration or hostility may arise if the physician repeatedly questions the patients’ preferences. Patients may even could comply or tolerate dialysis, despite their preference to withhold such treatment, when physicians convince them that this is a temporary procedure [ 31 ]. Finally, seriously-ill patients may struggle with their need to participate in emotionally complex discussions regarding their prognosis and treatment options, rendering them unable or unwilling to make decisions [ 32 ].

To the best of our knowledge, EOL care in ESRD patients has not been investigated in Israel from the nephrologists’ perspective. A recent study examined the nephrology nurses’ views of SDM practices among the nephrologists with whom they work [ 33 ]. In another study, family physicians perceived AD as a complex issue and lacked knowledge on PC [ 34 , 35 ]. Physicians have stated that they believe their EOL patients have the right to make decisions regarding life-prolonging treatment, yet some also claimed that such patients often receive unnecessary treatment [ 34 , 36 ]. In one study, about half the physicians deemed expensive treatments in EOL care unnecessary [ 36 ]. Some reported that they refrain from talking to their patients about their prognosis, or about the option of withdrawing treatment, simply focusing on providing PC instead. On the other hand, some physicians may succumb to the family’s demands to provide life-saving (and possibly futile) treatment [ 34 , 35 , 37 , 38 ].

Nephrologists and SDM

When conducting informed SDM regarding renal-replacement therapy [ 39 ], the nephrologist’ role is pivotal. The literature defines four different approaches to such decision-making processes: [ 1 ] Paternalists , who prioritize their patients’ health over their patients’ decision-making autonomy; [ 2 ] Institutionalists , who treat their patients according to the institution’s norms and culture; [ 3 ] Informativists , who prioritize their patients’ decision-making autonomy; and [ 4 ] Interpretivists , who develop strong ties with their patients, as a means for facilitating guided decision-making [ 40 ]. In general, the first two types of nephrologists (paternalists and institutionalists) would favor dialysis in most cases, while the latter two (informativists and interpretivists) focus on the patients’ engagement and their quality-of-life.

In the USA, nephrology medical directors encourage their teams to apply SDM for initiating or withdrawing dialysis, in line with the guidelines issued by the American Renal Physicians Association [ 19 ]. Yet when treating ESRD patients, nephrologists must overcome SDM-related concerns, in order to adequately convey the various options to their patients. Nephrologists with positive attitudes towards dialysis tend to report fewer barriers [ 41 ]. Although SDM has not been investigated in the field of nephrology in Israel, it has been researched in other medical fields [ 42 , 43 , 44 , 45 ]. Studies show that older, more experienced physicians usually address caregivers rather than the patients themselves; primary-care physicians also tend to make decisions together with the patient’s family [ 46 ]. Overall, SDM in Israel is perceived as feasible, and could lead to increased engagement and knowledge, improved medical outcomes, and better correspondence with the patients’ preferences [ 47 ].

Conceptual framework

The conceptual framework applied in this research study combines the following three theoretical SDM models: [ 1 ] practical SDM steps, including talking about choice, options, and decisions [ 48 ]; [ 2 ] SDM categories, including essential, ideal, and general SDM qualities [ 49 ]; and [ 3 ] three types of decision-making, including paternalistic, SDM, and informed decision-making [ 50 ] (see Annex 2 and Fig.  1 ). The research approach applied in this study included questionnaires for nephrologists, based on the theory developed by Emanual and Emanual (1992) and on the four models of physician-patient relationships (paternalistic, interpretive, informative, and deliberative) [ 51 ], as discussed above.

Conceptual Research Framework

Research hypotheses

Based on the literature review and the conceptual framework presented above, we propose the following two hypotheses:

H1: Nephrologists who act according to the interpretive and informative decision-making styles, and nephrologists who work in public or government dialysis clinics, will tend to support conservative treatment and focus on patient engagement, values, autonomy, and quality-of-life – compared to other respondents.

H2: Nephrologist who act according to the paternalistic decision-making style, and older nephrologists, will tend to prioritize patient health over autonomy, and be in favor of initiating dialysis as a measure of success – compared to other respondents.

Research design

This study applied a descriptive-quantitative approach for examining the perceptions of nephrologists in Israel in relation to SDM in ESRD patients. To do so, a cross-sectional descriptive questionnaire was compiled, based on the literature and on the theoretical models presented above (Annex 1).

Research population, sample, and sampling

Snowball and purposive sampling methods were employed to recruit respondents. The questionnaires were completed by 169 nephrology physicians. (According to official data from the Israeli Society of Nephrology and Hypertension (ISNH), this number constitutes about 60% of the nephrologist population in Israel.) Forty respondents completed the questionnaire in writing, while 129 completed it online. The respondents included nephrology physicians from hospitals and from community-based dialysis clinics throughout the country. Table  1 describes the research sample.

Data collection

First, a pilot study of the comprised questionnaire was conducted, delivered by post and by email to five physicians from nephrology units in Israel. Following their feedback and insights, the questionnaire was revised as needed. Using the QualtricsXM software, the final questionnaire was then posted on a range of online platforms, including eight professional Facebook groups and three WhatsApp groups. The questionnaire was also sent via Listserv to members of the ISNH, through snowball sampling and direct requests to participate. Printed copies of the questionnaire were also handed out at staff meetings and at two national nephrology conferences.

Data analysis

The data obtained from the questionnaires were analyzed using descriptive and inferential statistics. A range of associations and relationships between variables were examined in line with the conceptual background of this study, such as the respondents’ tendency to choose their patients’ health over their autonomy (or vice versa) and their age or years of experience in the field.

To test the research hypotheses, the following three primary variables were calculated: [ 1 ] Decision-making style. This variable was based on 27 items from the questionnaire, coded on a 1–5 scale (Cronbach’s α = 0.96). An average of all items was calculated and divided into three types: paternalistic (M ≤ 2), interpretive [ 2 , 3 , 4 ], or informative (M ≥ 4); [ 2 ] Health vs. autonomy. This variable was based on three items from the questionnaire, coded on a 1–5 scale (Cronbach’s α = 0.91). An average of all items was calculated. This variable was used as a continuous scale, whereby lower scores represented health , while higher scores represented autonomy ; and [ 3 ] Conservative vs. invasive treatment. This variable was based on 16 items from the questionnaire, coded on a 1–5 scale (Cronbach’s α = 0.84). An average of all items was calculated and divided into two types: invasive (M ≤ 3) and conservative (M ≥ 3). We used five different statistical tests for data analyses: Pearson correlations; Fisher’s exact test; t-tests for independent samples; Chi-square test for independence; and t-tests for independent samples.

Ethical considerations and approvals

This research study was approved by the Research Ethics Committee at the Faculty of Social Welfare and Health Sciences, University of Haifa (Approval #411/21, dated 13 July 2021). The respondents were informed that their participation was voluntary and that they could cease participation at any time whatsoever. A short description of the research aims, expected advantages, risks, confidentiality, expected duration for completing the questionnaire, and research funding were all presented on the first page of the questionnaire – after which the participants were asked to provide their informed written consent. Participation in the study was anonymous and complete confidentiality was maintained throughout the study. Additionally, all research tools and methods were applied in accordance with strict ethical standards, as published in the Declaration of Helsinki and its later amendments (or comparable ethical standards).

The findings of this study regarding SDM between nephrologists and ESRD patients in Israel are presented through descriptive and inferential statistics.

Respondents’ characteristics

Out of the 169 participants, 40 respondents completed a printed version of the questionnaire and 129 respondents completed an online version via a link that was posted on professional Facebook and WhatsApp groups. When examining the respondents’ personal characteristics, the research sample included 53.5% males and 46.5% females, and the respondents’ mean age was 50 years (SD ± 11). Most respondents were born in Israel (70.6%) and were married (78.7%). When asked about their nationality, 71.7% defined themselves as Jewish and 28.3% as Arabs, including 18.2% Muslim-Arabs and 10.1% Christian-Arabs. When asked about their religiosity, about 35.5% of the respondents defined themselves as secular, 24.4% as traditional, 32.2% as religious, and 7.9% as orthodox.

From a professional perspective, all respondents were general physicians; 81.7% were nephrologists and 18.3% also specialized in PC. Some respondents had more than one place of occupation: 78.7% worked in public hospitals (including 23.7% in government hospitals) and 8.9% in private hospitals. Additionally, 16.6% worked in private community dialysis clinics, either part-time or full-time. Finally, 74.3% reported working in central Israel, 47.8% in the Jerusalem region, 57.4% in the north of Israel, 37.7% in the south, and 7.3% in the Sharon region (Table  1 ).

SDM practices and perceptions

Most respondents agreed or strongly agreed that decision-making is flexible (80.1%) and is a process of partnership (81.1%); the respondents also tended to agree or strongly agree that they must take responsibility for the patients’ medical decisions (66.9%); that they must attempt to influence the patient’s decision-making and outcomes (64.6%); and that the physician’s role is limited, placing the decision-making responsibility on the patient (59.1%) (Fig.  2 ).

Decision-Making Processes

Some physicians (15.7%) reported making their final decision after consulting other professionals; only 5.5% of the respondents reported making the final decision without any consultation. Decision-making regarding care for ESRD patients was found to be most affected by professional considerations (91.1%), followed by emotional outcomes in relation to the specific case (65.7%). Issues such as legal liability, religious beliefs, self-esteem, workload, and the number of patients were only addressed by half the respondents.

Most respondents reported that they tend to make decisions together with other professionals, including other physicians, nurses, and social workers on the ward (77%), PC staff (64%), physicians outside the ward (56.8%), the hospital Ethics Committee (50.3%), and religious people from the patient’s surrounding (45.6%). Almost half the physicians strongly agreed that collaboration between teams improves patient care efficiency (48.8%), increases job satisfaction (42.1%), and decreases workload (37.8%).

Collaborations between healthcare providers were found to be most facilitated by providing consultations within the nephrology clinic (97.2%), yet least facilitated by promoting interpersonal relationships between healthcare providers (81.3%). Obstacles to conducting team collaborations included fragmented care (15%); specialists from different locations (14%); the patients’ and families’ reluctance to discuss referrals to other professionals (14%); and financial/administrative issues (13%) (Fig.  3 ).

Main Barriers to Collaborations between Teams

Regarding physician-patient communications, around 80% of the respondents believed that it is important to discuss all available treatment options with ESRD patients. About two-thirds believed that ESRD patients usually refrain from discussing their prognosis (67.1%), do not fully understand the consequences of withdrawing from dialysis (60.8%), and are prone to depression/anxiety (62.2%) – thereby hindering their decision-making abilities regarding EOL care.

About two-thirds of the respondents also believed that physicians regularly discuss quality-of-life with ESRD patients (66.9%), inquire about their preferred place of dying (61.5%), provide prognostic assessments (63.4%), ask their patients about AD/power-of-attorney, and inquire about their religious and cultural beliefs regarding EOL (57.4%). Finally, 20.1% reported never asking their ESRD patients about AD/power-of-attorney, while 58.6% claimed that they always do so.

Attitudes towards EOL training and care of ESRD patients

Most respondents reported having undergone training on EOL management and symptom management (68%), EOL-related legal issues (66%), and ADs and PC (62%). About 11% reported having received no special EOL training.

Most respondents stated that they feel comfortable conducting conversations with ESRD patients and their families regarding prognosis, quality-of-life, and treatment options (76.12%), managing PC for patients who have stopped receiving dialysis (73.69%), and assisting them in completing their AD or appointing power-of-attorney (72.94%). They also reported that they had received adequate training in managing and evaluating EOL among ESRD patients (71.86%).

Few nephrologists reported that they would always provide regular dialysis for patients over 75 (26%), with sepsis (14.2%), or with HIV (14.2%), yet would never do so for patients with advanced dementia (13.6%). PC was found to usually be offered to patients who are unconscious (7.1%) or have a life expectancy of < 3 months (8.9%); yet not for patients with sepsis (14.2%). Finally, few nephrologists reported that they would resuscitate ESRD patients over the age of 75 (8.3%), and would never suggest resuscitation for patients with a life expectancy of < 3 months (15.4%) or with advanced dementia (16%) (Fig.  4 ).

Dialysis as Usual, Resuscitation and Palliative Care in Hypothetical Conditions in ESRD Patients

Many respondents (65.7%) agreed or strongly agreed that providing dialysis to dying patients is equivalent to other life-saving treatments, which in Israel (according to the Dying Patient Act 2005, cannot be terminated, but may not be renewed. Overall, between two-thirds of respondents agreed that nephrologists should discuss CC or AD with ESRD patients, and refer them to PC (Fig.  5 ).

Respondents’ Beliefs regarding EOL Situations

Relationships between SDM styles and treatment decisions

According to our first hypothesis, interpretive and informative nephrologists, and those who work in public/government dialysis clinics, will tend to support CC, while focusing on the patients’ engagement, values, autonomy, and quality-of-life. This hypothesis was partially confirmed by the findings in this study. Informative nephrologists were found to prefer the value of autonomy over health ( P  < 0.00), were more in favor of conservative treatment – thereby referring to the concept of quality-of-life, and used less invasive treatments compared to other nephrologists ( P  = 0.02). Moreover, informative nephrologists focused more on values of autonomy and quality-of-life than on the patients’ health when making clinical decisions ( p  < 0.0001).

According to the second hypothesis, paternalist and older nephrologists will tend to prioritize their patients’ health over their autonomy, and will be in favor of initiating dialysis as a measure of success. This hypothesis, however, was not confirmed, as the research sample did not include nephrologists who typically act in accordance with the paternalistic decision-making style. Instead, 47% of respondents reported applying an interpretive decision-making style, and 53% reported applying an informative one. Additionally, no significant correlations were seen between age and the tendency to promote the patient’s health and initiate dialysis rather than promoting their autonomy. Finally, nephrologists from the public/government organizations were not found to prefer CC to more aggressive care compared to those who work in private institutions.

Providing EOL care for ESRD patients

This study investigated the extent to which nephrologists in Israel pursue an SDM decision-making model when providing EOL care for ESRD patients. Specifically, the study explored different patterns of decision-making processes that can be applied in EOL situations, and that stem from a variety of reasons. First, the categories describing EOL situations are not clear-cut (as seen in Sect. 4.3 above). Second, a gap may exist between the respondents’ declared and actual actions, allowing for a wide range of options and fluctuations. Third, the research sample was diverse in terms of age, experience, workplace, and other variables. Such a dynamic approach to EOL care within nephrology has been previously observed in studies conducted outside Israel [ 39 , 50 , 52 ]. Moreover, nephrologists may transition between models and approaches in terms of the degree of SDM and communications between the various parties [ 49 ].

Davison and colleagues (2006) [ 53 ] found that young nephrologists from Canada reported stopping dialysis more frequently than nephrologists from the USA, especially in cases of severe dementia (as seen in this study), although they practiced medicine in units that were less likely to have policies on dialysis withdrawal. Additionally, unlike a previous study [ 54 ], no relationships were seen between the physicians’ age and their referring ESRD patients to PC. This may be due to the relative high importance that is awarded to sanctity of life in Israel, compared to other Western countries [ 33 , 52 ].

Cultural explanations

In this study, some (albeit few) respondents were willing to initiate dialysis or resuscitation for patients over the age of 75 without additional co-morbidities. The desire to offer optimal care for the elderly exemplifies the Israeli ethos to care for elderly patients at almost any cost [ 55 ], unlike other societies where nephrologists are less inclined to begin renal-replacement therapy in such patients [ 56 ]. More generally, it represents a tendency among physicians in Israel to preserve life, even with poor quality-of-life [ 34 , 57 ], which reflects a shift in the attitudes of healthcare professionals in Israel towards PC [ 58 ]. Yet unlike our expectations, and as demonstrated in a study conducted in Germany on the opinions and practices of head physicians in renal centers [ 59 ], no tendency to offer CC was seen in public institutions compared to private ones.

Nephrologists’ decision-making styles

One of the most dominant findings of this study is that no respondents from the research sample conveyed that they employ a paternalistic decision-making style. Moreover, about 80% of the respondents believed that it is important to discuss all available treatment options with ESRD patients. These findings are in line with Yagil & Medler-Liraz, (2015) [ 60 ], who found that family physicians in Israel use various tactics for providing guidelines, maintaining their professional identity, and involving patients in the decision-making process. Yet these findings are in contrast to a study by Einav and colleagues, where intensive-care physicians in Israel were found to be more paternalistic than their counterparts in the USA [ 61 ]. It may be that nephrologists give more weight to their patients’ preferences than other physicians.

In this study, almost 60% of the participating nephrologists stated that it is the physician’s responsibility to influence the patient’s decision-making, with most applying interpretive and informative decision-making styles. Moreover, the study shows that one main factor that impacts the decision-making process is the possible emotional outcome of the nephrologist-patient discussions and communications on all parties involved, especially the patients and their families. To reduce this burden, nephrologists may implement different decision-making styles – such as paternalistic, informed, or SDM. They may also avoid conducting such direct discussions, by simply convincing their patients to undergo dialysis. Alternatively, they might transfer the decision-making responsibility to the patients, or conduct time-limited trials of dialysis [ 18 ].

The study also reveals that informative nephrologists prefer the value of autonomy over health, are more in favor of CC, and use less invasive treatments –compared to interpretive nephrologists. In a qualitative study by Ladin et al. (2018) [ 40 ] on decision-making in nephrology, five themes were found to differentiate between the four decision-making styles: [ 1 ] patient autonomy; [ 2 ] engagement and deliberation; [ 3 ] the influence of institutional norms; [ 4 ] the importance of clinical outcomes; [ 5 ] and the physician’s role. Paternalist nephrologists were found to view dialysis initiation as a measure of success, while advocating for dedication to patients and commitment to treatment. On the other hand, interpretive and informative nephrologists were found to focus on patient engagement and quality-of-life, while aligning the treatment with the patients’ values. Interpretive nephrologists were also found to place an emphasis on trust and on the understanding of their patients’ preferences. Similar to the current study, informativists perceived patient autonomy as the most important component in the decision-making process, enabling patients to enjoy the life they have left and live it with dignity. Yet only one-third of the informative and interpretive physicians in their study offered CC to their patients – unlike the findings of the current study.

Content of nephrologists’ communications with ESRD patients

In the current study, about two-thirds of the respondents reported that they always provide their patients with prognostic assessments, discuss quality-of-life with them, inquire about their preferred place of death, and ask about their religious and cultural beliefs regarding death and dying. These findings are in line with the guidelines issued by the American Renal Physicians Association, whereby implementing SDM is recommended, as a means for reaching shared understandings and agreements based on common ground [ 21 ] as well as with studies conducted outside of Israel, where physicians reported a more direct involvement of patients in the decision-making process [ 62 , 63 ]. These findings, however, are contrary to a recent study where Israeli healthcare professionals conveyed their hesitance about engaging patients in SDM [ 64 ]. Future research should gather more empirical and objective data on the topic, as a means for further understanding the practice of SDM, for example, through surveying patients or analyzing videotape consultation during such processes [ 65 , 66 ].

Patients’ perspectives on SDM

Indeed, examining the patients’ perspectives on SDM is of great importance [ 67 ]. Increased satisfaction with their received healthcare services and decreased anxiety were seen among patients who were involved in their treatment-related decisions through participation in educational programs related to their specific illness (where a range of aspects were addressed, such as symptoms, clinical outcomes, and the impact of the disease on their lives). They also reported increased knowledge, adherence to treatment, physical outcomes, efficient utilization of health services, and decreased rates of hospitalization [ 68 ].

In a study that examined decision-making in ESRD patients, 27% of the participants reported that they made their own medical decisions alone, 24.5% shared the responsibility, and 48.4% relied on their healthcare providers. Older patients reported a more passive role and greater reliance on their healthcare teams, compared to younger patients [ 43 , 62 ]. Another study found two competing views on decision-making among patients. According to the first view, patients reported a lack of understanding regarding SDM, including limited familiarity with the concept, low acceptance of this process, insufficient information, and lack of autonomy within familial relationships. Yet according to the second view, patients reported that healthcare professionals advocate for SDM, conservative treatment, and EOL care, thereby facilitating advanced decision-making among patients [ 65 ]. A study from the USA further revealed that nephrologists are trained to enhance SDM in dialysis-related decisions for older patients with life-limiting ESRD, using a best-case/worst-case decision-making tool (i.e., life with dialysis and life without dialysis). Patients and family members who were exposed to this tool reported that it allowed them to deliberate about the treatment options, anticipate what life with dialysis might be like, and prepare them for the future. Moreover, patients who were exposed to this tool supported SDM because they had been given options [ 69 ].

In a recent study, younger nephrology patients were found to value autonomy and their current lives, while older patients tended to focus on “the rest of their lives,” spending time with their families, and preparing for death. The study presents a conceptual model for how older patients decide whether to choose dialysis or CC, based on the following three concepts: [ 1 ] reflecting on treatment options in relation to physical frailty and mental health; [ 2 ] confronting difficult decisions by considering the need to receive and manage clear information, rather than burdening the family caregivers; and [ 3 ] maintaining hope, by choosing to live the rest of their lives with peace and dignity, knowing that they may not have long to live [ 70 ].

In an Israeli study on the attitudes of ESRD patients towards dialysis and transplantation, priority was given to younger patients, who were perceived as having better life expectancy than older patients, as well as other improved physical prospects [ 71 ]. However, data is lacking on patients’ perspectives and experiences regarding SDM.

Studies show that patients in Israel wish to be involved in treatment decisions [ 42 , 43 ] and in SDM processes [ 72 ], and that in general, the Israeli public is ready for increased engagement and information regarding their healthcare [ 73 ]. Indeed, progress can be seen, for example, through the increasing engagement of patients with chronic diseases and their families, following patient centered care (PCC) and SDM approaches, as well as public policies [ 64 ]. However, most patients do not feel ready to be involved in their consultations [ 43 ], and prefer decisions to be made by their physicians [ 74 ]. Some patients are reluctant to engage in active decision-making, since they believe that they lack adequate medical understanding and knowledge of up-to-date studies. As such, patients vary in the degree to which they wish to take part in the decision-making process regarding their own health [ 74 ]. To achieve further progress in PCC and SDM in Israel, one healthcare organization encourages patients to use the “Ask Me Three” tool, that helps them ask their physician specific questions about their condition, what should be done to treat it, and why that course of treatment is important or correct [ 64 ]. Yet, there is still room for improvement in implementing and maintaining PCC and SDM [ 44 ]. To enhance SDM in Israel, data must be collected, analyzed, and stored in an organized and accessible manner; adequate healthcare infrastructure should be provided; awareness of this process must be increased; and decision-making tools should be developed and then implemented by both medical teams and patients [ 64 , 75 ].

Making treatment choices at EOL and advance directives

In the current study, a clear divide was found between nephrologists who never ask patients with ESRD about their AD/power-of-attorney compared to those who always do so. This finding contradicts our expectations, whereby nephrologists bear the responsibility for guiding patients on such matters [ 53 ]. Treatment choices near EOL are not simple or predictable; rather, they are uncertain and complex. The aim of advance care-planning is to support patients when they lack decisional capacity and are unable to understand or share their medical preferences in the future. Yet, as studies and practices show, AD do not suffice. In some cases, their existence may even inhibit discussions, leading to present decisions being made based on documents that are supposed to be used in the future [ 76 , 77 ]. Empathic listening may be the key to alleviating the patient’s uncertainty in making decisions regarding EOL care. It can help patients feel less overwhelmed, tolerate their prognosis with greater ease, and increase their adherence to treatment [ 78 ].

Professional, emotional, cultural, and organizational aspects of EOL decision-making

Finally, when reviewing factors that impact decision-making for ESRD patients, this research found both professional considerations and emotional consequences to be most influential – similar to other studies [ 79 , 80 ]. Moreover, the current study found that the patients’ religious beliefs play a role in the decision-making of about half the nephrologist who completed the questionnaire. According to previous studies, maintaining life-support is a cultural value that is embedded in religion [ 81 , 82 ]. Our study also found that the physicians’ decision-making practices were impacted by their legal responsibility, workload, and the number of patients that they tend to treat within a given period. Our findings are also in line with another study, where factors that were central to EOL decision-making included the physicians’ professional experience, legal issues, and patient-related factors, such as their wishes and prognosis, and the requests of the patients and their families. The least influencing factors in decision making were hospital-related variables, such as specialization, medical hierarchy, and time pressure [ 83 ].

Policy implications

The varied findings presented in this study offer a number of important policy implications regarding care-provision and decision-making for ESRD patients. These include the following:

The findings of this study indicate that nephrologists in Israel are not paternalistic. Theoretically, they acknowledge the important role of the patients within the SDM process. Yet, in practice, they do not always involve the patients, with whom their communications are rather limited. To minimize this gap, healthcare professionals should be encouraged to increase their patients’ awareness of SDM. Moreover, healthcare organizations should also develop and offer educational programs, tools, and modalities – especially suited to recurring nephrology patients, who could learn more about their illness and its impact on their lives and on their clinical condition. Doing so will enhance the patients’ knowledge and willingness to engage in SDM [ 74 ]; improve their ability to ask questions [ 44 ]; increase their desire to deliberate about treatment choices and dialysis [ 69 ]; support decisions related to kidney-failure treatment modalities [ 84 ]; improve adherence to treatment; and advance their substantial participation in SDM [ 68 ].

The study found that the majority of nephrologists perceived SDM as a process of partnership between multi-disciplinary teams. Most respondents claimed to consult other professionals, especially nephrologists and nurses, yet not physicians of other specialties, nor social workers or PC staff. Establishing and maintaining co-working and consultation conditions between nephrologists and other professionals could contribute to SDM processes and outcomes.

As many of the nephrologists do not ask their patients about AD or power-of-attorney, physicians and nurses who provide care to ESRD patients should be encouraged to hold such conversations with their patients, while providing them with the necessary knowledge and assistance for completing the required forms. Doing so will greatly facilitate SDM in future encounters with these patients. Moreover, increasing the percentage of ESDR patients who tend to such issues in advance should be a key target in medical institutions; this could also serve as an additional factor in the accreditation process of these institutions.

More generally, in order to improve SDM processes regarding ESRD patients, trainings on EOL care and ethics should be conducted regularly, for both nephrologists and nurses. Such programs could better equip healthcare providers for conducting SDM processes, while improving their communication skills required for SDM, emphasize the importance of listening, and showing empathy to the patient. Such trainings could also include SDM simulations, and offer an SDM checklist (which could be created using artificial intelligence). This would help healthcare providers offer greater support for their patients when making decisions about their treatment, allowing them to weigh their options in a more informed manner [ 85 ].

Finally, the ISNH should consider issuing guidelines – similar to those published by the American Renal Physicians Association. Doing so will convey a clear statement as to the importance of implementing SDM when treating ESRD patients. Combined with the recommendations presented above, this top-down approach will help internalize the effective practice of SDM in nephrology units across Israel, and in turn, may inspire additional medical fields and practices to also do so.

Strengths and limitations of the study

This study focused on nephrologist-ESRD-patient SDM. As such, generalization of these findings to other physicians and fields should be made with caution. However, as a very high percentage of nephrologists responded to the survey, the findings are highly indicative of the views and attitudes of the researched population.

The topic of SDM was only examined from the physicians’ perspective, not the patients’ perspective. It may be argued that the design and findings of this study reinforce a paternalistic view of the clinician-patient relationship, which assumes that decisions should be made solely or chiefly by physicians [ 86 ]. Yet no paternalistic pattern of SDM was seen among the surveyed nephrologists in the current study. Future research could benefit from examining the perceptions of nephrology patients, in addition to physicians in this field, for means of comparison and for identifying discrepancies between the attitudes of these two populations. Regardless, our report of this finding in itself is strong enough to refute this concern. Additionally, the study did also examine and report other findings regarding the patients’ attitudes and capabilities, albeit indirectly, through the nephrologists’ input.

Certain bias may have occurred in the data collection, as the questionnaire employed in this study was relatively long; as such, certain groups of respondents – such as those who are greatly in favor of or against SDM – may have invested in completing this survey. Yet the 169 questionnaires that were completed in full provide a large sample size in itself, and also represent about 60% of the entire nephrologist population in Israel, which is considered a desirable rate [ 87 ]. Additionally, as a cross-sectional study, this research does not claim to represent the entire population.

Not only does this study describe the actual practices of SDM in EOL nephrology care; it also examines important associations between SDM and the nephrologists’ attitudes towards ethics during EOL care, thereby providing important evidence for further examining the practice of SDM in Israel.

Nephrologists in Israel only partially pursue the SDM model. They tend to ask patients about their AD or power-of-attorney, and inquire about their religious and cultural beliefs regarding EOL. Yet when providing care to ESRD patients with complex cases, these physicians may decide to take sole responsibility for the decision-making, regarding withholding or withdrawing from dialysis, for example, or when referring patients to PC. Additionally, nephrologists in Israel are not paternalistic, and are aware of the patients’ important role in the SDM process. However, enhancing SDM in nephrology programs in Israel is highly recommended – with an emphasis on the importance of listening to patients, conveying empathy, enhancing patient knowledge, and improving communications between patients and healthcare providers. Doing so will be beneficial for all parties involved.

Annex 1. The Questionnaire

The questionnaire that was comprised for this study included 92 items, most of which were close-ended questions, where the respondents were asked to rate each item on a Likert-like scale; 12 items were open-ended questions. The questionnaire mainly focused on existing items from validated questionnaires that have been published in the literature, which were then translated into Hebrew. The questionnaire was comprised of four sections. The first section included 12 biographical questions, such as age, marital status, work experience, and type and location of workplace. The second section of the questionnaire was adapted from the Clinician Perspectives on Palliative Care in Kidney Disease Questionnaire [ 28 ], and included seven items about the respondents’ education and training in EOL care and decision-making. Two items were close-ended questions that aimed at assessing the participants’ medical training (items 13, 14). Five items were related to the respondents’ training in EOL care management and providing patients with assistance in preparing their AD or appointing power-of-attorney (items 15–19), which the respondents were asked to rate on a Likert-like scale, from 1 (strongly disagree) to 5 (strongly agree). For example, “I feel confident in managing PC for patients who have stopped receiving dialysis and their families,” or “I feel comfortable holding conversations with ESRD patients and their families regarding the prognosis.” The first author of this paper received the questionnaire and related input from the first author of the original questionnaire via email [ 28 ]. The questionnaire had undergone validity tests, including extensive pilot testing that entailed the completing of the questionnaire by experts in the field, following by their submitting a survey about the questionnaire comprised of both open-ended and multiple-choice questions.

The third section of the questionnaire was in line with the conceptual framework of this research [ 48 , 49 , 50 , 88 ]. These 40 items, which were organized into three groups of questions, examined the respondents attitudes and practices regarding SDM, based on the key elements suggested by these theoretical models: [ 1 ] The first group of the questions (items 20–31), which were adapted from Makoul and Clayman (2006) [ 49 ], assessed whether the respondents define the problem for the patient during the decision-making process, for example, or whether they offer the patient free choice regarding the proposed treatment; [ 2 ] The second group of questions (items 32–36) were adapted from Charles and colleagues (1999) [ 50 ] and Makoul & Clayman (2006) [ 49 ]. These items asked respondents to rate their level of agreement with various statements, on a Likert-like scale from 1 (strongly disagree) to 5 (strongly agree), such as the physician’s ability to influence the patient’s decision-making process and its outcome, and whether they regard the decision-making process as a process of partnership; [ 3 ] The third group of questions (items 37–38), which were adapted from Charles and colleagues (1999) [ 50 ], aimed at assessing who the physician tends to involve when making decisions regarding ESRD patients using close-ended multiple choices questions. The following questions (items 39–41, 44–45) were adapted from Ceckowski and colleagues (2017) [ 29 ]. These items referred to decision-making processes with regards to several situations, such as an ESRD patient who suffers from depression, or whose family has limited understanding of PC and hospice care. Items 42–43, 46–51, 52–59 of the questionnaire were adapted from Metzger and colleagues (2021) [ 28 ] and were aimed at assessing the extent to which respondents provide prognostic assessments, for example, and whether they discuss all treatment modalities with their patients. For these items, the respondents were asked to choose their rate of agreement (on a scale of: never , rarely , sometimes , often , and almost always .) For other items, the respondents were asked to provide specific input, such as “What is the most prominent obstacle” (Item 53) or “What percentage of your patients have prepared advance medical directives?” (Item 54).

Finally, the fourth section of the questionnaire included 33 items that referred to EOL care for patients with ESRD, and to the nephrologists’ attitudes towards such care, based on Lunney et al.‘s (2002) categorization of EOL care [ 89 ]. Items 60–62 included open-ended questions, which asked respondents to address issues such as a possible age limit for withdrawing patients from dialysis, their perceived role of PC, and the complexity of providing care for ESRD patients. Items 63–70, which were adapted from Hong and Colleagues (2021) [ 25 ], aimed at assessing how nephrologists would act based on a list of care alternatives in various hypothetical scenarios, for example, dialysis as usual, referral to PC, and resuscitation when needed. For example, when the patient is over 75 years old; has a life expectancy of up to three months; or has cancer. The respondents were asked to rate each item on a Likert-like scale, from 1 (almost never true) to 5 (almost always true). Item 71 was adapted from Fung and Colleagues (2016) [ 19 ] and explores what best describes the physician’s decision-making process based on a close-ended multiple-choice question. Items 72–73 aimed at assessing workplace practices with regards to SDM [ 90 ]; items 74–75 were adapted from Metzger and colleagues (2021) [ 28 ] and aimed at exploring the reasons for referring ESRD patients to PC.

The next items [ 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 ], which were adapted from Hong and colleagues (2021) [ 25 ], aimed at assessing how often clinicians meet with ESRD patients in the various scenarios suggested above. The respondents were asked to rate each item on a Likert-like scale, ranging from 1 (less than five patients per month) to 5 (more than 20 patients per month). Finally, items 84–85, which were also adapted from Metzger and colleagues (2021) [ 28 ], explored the respondents’ attitudes towards the consequences of referring patients to PC, based on a Likert-like scale from 1 (strongly disagree) to 5 (strongly agree). Regarding Items 86–92, Item 86 was adapted from Ceckowski and colleagues (2017) [ 29 ] and aimed at assessing the respondents’ willingness to refer patients to a hospice if they can undergo hemodialysis. Items 87 and 92 were adapted from Perry et al., 1996 [ 91 ], in an aim to assess the respondents’ attitudes towards providing care for EOL patients. Item 88 was aimed at assessing whether the nephrology staff discusses CC with patients in advanced chronic kidney disease. Items 89–91 were adapted from Hong and Colleagues (2021) [ 25 ], aimed at assessing respondents’ beliefs, for example, regarding the nephrology staff’s role in saving or prolonging the lives of ESRD patients, on a Likert-like scale from 1 (strongly disagree) to 5 (strongly agree). The research questionnaire is in Hebrew and can be re-used by the authors’ permission upon request.

Annex 2: The Conceptual Framework

The conceptual research framework combines the following theoretical SDM models, each comprised of three sections: [ 1 ] practical SDM steps; [ 2 ] SDM categories; and [ 3 ] types of decision-making (Fig.  1 ).

The three practical SDM steps for clinical practice include a choice talk , where physicians ensure that the patient is presented with reasonable care/treatment options; an options talk , where physicians must provide patients with additional information about the various options; and the decision talk , where physicians must consider the options and preferences and then choose the optimal option for the patient [ 48 ].

The three SDM categories include essential SDM elements , comprised of defining the medical issue, presenting an option, discussing benefits, risks and costs, exploring patient values and preferences, discussing patient ability and self-efficacy, exploring the doctor’s knowledge and recommendations, checking the patient’s understanding, making or deferring decisions, and arranging follow up; ideal SDM elements , comprised of introducing unbiased information, defining roles, presenting evidence, and reaching a mutual agreement; and general SDM qualities , comprised of deliberating and negotiating, applying a flexible and individualized approach, exchanging information, involving at least two people, finding middle ground, acting with mutual respect, seeking a partnership, enhancing patient education and participation, and deciding on the process/stages [ 49 ].

The third and final model of the conceptual framework for this research is offered by Charles and colleagues [ 50 ], who in revising an earlier framework (1997) propose three types of decision-making in relation to choosing the patient’s recommended course of treatment. The first type is paternalistic , where physicians have full authority to determine the treatment that is to be implemented. The second type is SDM , where the physician and patient jointly discuss and choose the treatment that is to be implemented. Finally, the third type relates to informed decision-making, where the patient has the exclusive authority to make decisions regarding their own treatment.

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

Advance directives

Conservative care

• End-of-life
• End-stage renal disease

Palliative care

• Shared decision-making

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Acknowledgements

The researchers would like to acknowledge Dr. Gil Chernin, Chair of the Israeli Society of Nephrology and Hypertension for delivering the link to the research questionnaire to the Society’s members.

This study received funding from the Minerva Center for Interdisciplinary Study of End-of-Life at the Tel-Aviv University.

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Hatoum, W.B.A., Sperling, D. Shared decision-making in end-of-life care for end-stage renal disease patients: nephrologists’ views and attitudes. Isr J Health Policy Res 13 , 45 (2024). https://doi.org/10.1186/s13584-024-00632-w

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DOI : https://doi.org/10.1186/s13584-024-00632-w

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• Consensus Statement
• Published: 03 April 2024

Chronic kidney disease and the global public health agenda: an international consensus

• Anna Francis 1 ,
• Meera N. Harhay 2 , 3 ,
• Albert C. M. Ong   ORCID: orcid.org/0000-0002-7211-5400 4 ,
• Sri Lekha Tummalapalli 5 , 6 ,
• Alberto Ortiz   ORCID: orcid.org/0000-0002-9805-9523 7 ,
• Agnes B. Fogo 8 ,
• Danilo Fliser 9 ,
• Prabir Roy-Chaudhury 10 ,
• Monica Fontana 11 ,
• Masaomi Nangaku 12 ,
• Christoph Wanner   ORCID: orcid.org/0000-0001-9507-5301 13 ,
• Charu Malik 14 ,
• Anne Hradsky 14 ,
• Dwomoa Adu   ORCID: orcid.org/0000-0002-2606-2117 15 ,
• Sunita Bavanandan 16 ,
• Ana Cusumano 17 ,
• Laura Sola   ORCID: orcid.org/0000-0003-3269-3908 18 ,
• Ifeoma Ulasi   ORCID: orcid.org/0000-0001-7783-3025 19 ,
• Vivekanand Jha   ORCID: orcid.org/0000-0002-8015-9470 20 , 21 , 22 ,
• American Society of Nephrology ,
• European Renal Association &

International Society of Nephrology

Nature Reviews Nephrology volume  20 ,  pages 473–485 ( 2024 ) Cite this article

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• Acute kidney injury
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Early detection is a key strategy to prevent kidney disease, its progression and related complications, but numerous studies show that awareness of kidney disease at the population level is low. Therefore, increasing knowledge and implementing sustainable solutions for early detection of kidney disease are public health priorities. Economic and epidemiological data underscore why kidney disease should be placed on the global public health agenda — kidney disease prevalence is increasing globally and it is now the seventh leading risk factor for mortality worldwide. Moreover, demographic trends, the obesity epidemic and the sequelae of climate change are all likely to increase kidney disease prevalence further, with serious implications for survival, quality of life and health care spending worldwide. Importantly, the burden of kidney disease is highest among historically disadvantaged populations that often have limited access to optimal kidney disease therapies, which greatly contributes to current socioeconomic disparities in health outcomes. This joint statement from the International Society of Nephrology, European Renal Association and American Society of Nephrology, supported by three other regional nephrology societies, advocates for the inclusion of kidney disease in the current WHO statement on major non-communicable disease drivers of premature mortality.

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Introduction.

In 2015, United Nations member states agreed on the ambitious Sustainable Development Goals (SDGs), with the aim to end poverty and inequality, protect the planet and ensure that all people enjoy health, justice and prosperity. An important health-related target is the reduction of non-communicable disease (NCD)-related mortality by one-third by 2030 (ref. 1 ). The WHO) has listed heart disease, stroke, cancer, diabetes and chronic lung disease as the five major NCDs driving premature death and disability 2 . Notably absent from this list is kidney disease, either acute kidney injury (AKI) or chronic kidney disease (CKD); of note, AKI increases the risk of CKD and vice versa 3 , 4 , 5 , 6 . Additionally, kidney disease commonly occurs with, and enhances the risk of, major NCDs such as ischaemic heart disease, stroke and peripheral vascular disease, diabetes and cancer 7 , 8 .

Approximately 850 million people worldwide are estimated to have kidney disease, most of whom live in low-income and lower-middle-income countries (LICs and LMICs), and a large proportion of these individuals lack access to kidney disease diagnosis, prevention or treatment 9 . As many as 9 out of 10 individuals with CKD in resource-poor settings with weak primary care infrastructure are unaware that they have this condition and therefore do not seek treatment 10 , 11 , 12 . Ageing populations and population growth will translate to large increases in the prevalence of CKD in LICs and LMICs in the coming decades. In contrast to cardiovascular disease, stroke and respiratory disease, CKD mortality has been rising. Currently, kidney disease is the third fastest-growing cause of death globally and the only NCD to exhibit a continued rise in age-adjusted mortality 13 . By 2040, CKD is projected to be the 5th highest cause of years of life lost (YLL) globally 14 .

Population growth, ageing and the increasing burden of diabetes, heart disease and hypertension are the best-recognized drivers of CKD incidence, especially in regions with advanced economies. As many as 1 in 3 people with diabetes and 1 in 5 with hypertension in high-income countries (HICs) have CKD, which has led to the suggestion that focusing on the control of diabetes and cardiovascular disease will alleviate the growing burden of CKD 15 . This assumption is based on the premise that screening for CKD is part of the standard of care for these conditions and that no special interventions are required in those with kidney diseases. However, CKD and AKI have diverse causes, mediators and risk factors beyond diabetes and cardiovascular disease (Fig.  1 ), especially in LICs and LMICs, which account for two-thirds of the global burden of kidney disease 16 . For example, dehydration and infections are leading causes of AKI in LICs and LMICs 17 . Finally, the latest research shows that CKD and AKI require unique treatments and are not merely risk enhancers when they accompany other major NCDs.

Although chronic kidney disease (CKD) shares several risk factors with the non-communicable diseases (NCDs) recognized by the WHO as major drivers of premature mortality — heart disease, stroke, cancer, diabetes and chronic lung disease — several other major causes of CKD, including acute kidney injury (AKI), contribute to the relentless rise in the global burden of kidney disease. Consequently, addressing only the WHO-recognized NCDs will be insufficient to reduce the growing negative impact of CKD .

In this Consensus Statement, we discuss the unique environmental, social and medical drivers of kidney diseases, highlighting how tackling diabetes and heart disease alone will not target the core drivers of a large proportion of kidney diseases. We also discuss how such an approach worsens global inequities in access to the best attainable standards of health and hinders progress towards targets identified in the SDGs, making the absence of kidney disease from the global NCD health agenda morally indefensible and a substantial challenge to tackling the growing kidney disease burden.

The International Society of Nephrology (ISN), European Renal Association and the American Society of Nephrology convened a diverse core group of 19 experts representing HICs and LICs in the Americas, Africa, Europe and Asia–Pacific, across adult and paediatric nephrology. Over several meetings, the authorship team discussed current and future challenges, as well as strategies for increasing global awareness of CKD and decreasing its global impact, to develop this Consensus Statement and recommendations. The manuscript was reviewed by various regional representative bodies (ISN Regional Boards), and consensus was attained. The ISN has established a regional board in each of its 10 regions — Africa, Eastern and Central Europe, Latin America and the Caribbean, Middle East, New Independent States and Russia, North America and the Caribbean, North and East Asia, Oceania and Southeast Asia, South Asia and Western Europe. The Regional Boards have representation from all affiliated societies within the region and are a major link between the ISN and National Societies of Nephrology.

Endorsement was also provided by other major global and regional societies, namely the Asian Pacific Society of Nephrology, African Association of Nephrology, Latin American Society of Nephrology and Hypertension and the World Heart Federation.

Kidney disease is a growing global problem

Kidney disease is an increasing global problem that disproportionately affects poor, vulnerable and marginalized populations, and is associated with high individual, health care and societal costs. Approximately 700 million people are estimated to have CKD worldwide. To this must be added the global burden of AKI and kidney failure (including those receiving dialysis and kidney transplant recipients), which increases the global prevalence of kidney disease to ~850 million 7 , 9 , translating to a global prevalence >10%. Of note, this prevalence is probably an underestimate owing to the lack of early kidney disease detection and screening programmes in many parts of the world, which results in large-scale unawareness of the burden and prevalence of earlier stages of CKD 11 .

AKI affects 7–18% of hospitalized patients and 20–200 per million individuals annually in the community 18 . AKI is most common in LICs and LMICs, where 75% of cases are community acquired owing to infections, toxins (for example, from animal bites, herbs and medications) and pregnancy complications 19 , 20 . According to a systematic review, an estimated 13.3 million cases of AKI are recorded worldwide every year, with LICs and LMICs contributing 11.3 million 21 . Of the 1.7 million deaths per year from AKI globally, an estimated 1.4 million occur in LICs and LMICs 18 .

Furthermore, the burden of kidney disease is rising worldwide. According to the Global Burden of Disease (GBD) study 7 , the global prevalence of CKD increased by 33% between 1990 and 2017. Crucially, the greatest growth in the burden of CKD (prevalence and mortality) is concentrated outside of HICs, with almost one-third of all patients with CKD living in India and China alone 7 . Beyond population dynamics, numerous other social, environmental and economic threats increase the global risk of kidney disease (Fig.  1 ).

Given its increasing prevalence, if CKD remains largely undetected and is consequently not treated, the numbers of people developing kidney failure and requiring expensive kidney replacement therapy (KRT) will naturally increase. In 2010, ~2.6 million people received KRT, and this number is estimated to increase to 5.4 million by 2030 (ref. 22 ). Even in HICs, 15–20% of patients die within 12 months of starting dialysis 23 . Millions more develop kidney failure and require KRT but lack access to therapy and die prematurely 24 , 25 . Almost all of these people live in LICs and LMICs, which have only 7% of the global KRT population despite comprising 48% of the world population 24 . AKI and progressive CKD are also associated with high mortality even before the development of kidney failure, primarily owing to an increased risk of other major co-morbidities 7 , 18 . A greater number of people die of cardiovascular disease directly attributable to reduced kidney function than of kidney failure-related deaths 26 , with the GBD study attributing ~3.1 million deaths in 2019 to kidney dysfunction.

Population dynamics will increase the burden of kidney disease

Population dynamics are increasing the numbers of people at a high risk of kidney disease but with limited access to kidney care. This effect is driven both by population growth and an ageing population. Population growth is booming in LICs and LMICs (especially in Africa and India) — Central and Southern Asia, Eastern and South-Eastern Asia, and sub-Saharan Africa are expected to hold 70% of the world’s population by 2030 (refs. 27 , 28 ). The age-standardized rate of CKD has already increased by 3–5% between 1990 and 2017 in countries in the lowest three sociodemographic index quintiles 7 . The highest growth in the number of people requiring KRT is projected for Africa, where 23 of the 28 poorest countries in the world are located 22 . Policies aimed at decreasing the burden of other NCDs that do not target CKD in these countries will generate an additional CKD burden. The reasons for the increased risk of CKD in LICs and LMICs are explored further below.

An ageing population faces an inherently increased risk of kidney disease. Current predictions estimate that by 2035, as many as 1.1 billion people will be over 65 years of age, an increase of 60% from 2020, with the largest number of older individuals expected to be in China and India 27 . The controversies with regard to age-adjusted definition of CKD notwithstanding, the rising prevalence of CKD translates to an increased risk of adverse outcomes in individuals in all age groups 29 , 30 , 31 . The loss of kidney reserve with ageing also exacerbates the bidirectional interplay between AKI and progressive CKD risk 32 . Moreover, CKD is associated with inflammation and accelerated whole-body ageing, particularly of the cardiovascular system, thereby increasing the burden of ageing-associated health decline even in younger patients 22 , 33 .

Environmental and social threats to kidney health continue to rise

The burden of CKD risk factors that traditionally drive disease in HICs, such as diabetes, hypertension and obesity, is growing most rapidly in LICs and LMICs. Moreover, LICs and LMICs face a constellation of additional risks that translate to a greater kidney disease burden than that seen in HICs 16 . Risks related to environmental change, including global warming, environmental toxins, air pollution and declining biodiversity, are global. However, the lack of capacity and resources for mitigation and adaptation makes LIC and LMIC populations particularly vulnerable to such risks. These populations also continue to have high rates of infectious diseases, many of which affect the kidneys 19 , 34 , 35 . The lack of resources in these countries means that the contribution of local CKD risk factors is not as well-studied as those related to diabetes or cardiovascular disease that were first recognized in HICs, which leads to their continued under-recognition. Superimposed onto this background, limited public health architecture and high poverty levels create life-course threats to kidney health, with a particular impact on pregnancy and childhood.

Fragile and underfunded health systems struggle to cope with the burden of kidney disease, leading to high and increasing mortality. Regional variations in the distribution of risk factors and the ability to implement adaptation measures mean that, in some places, CKD is an even bigger threat than that observed at a global level. For example, in Central America, CKD is the second most common cause of death 7 . Even in HICs, social determinants of health and factors such as gender, race or ethnicity influence the risk of kidney disease and underscore many health outcome disparities 36 , 37 , 38 , 39 . Race, for example, is increasingly recognized as a social construct, highlighting that its impact on kidney health is potentially modifiable 40 .

Environmental factors and climate instability contribute to the increased risk of kidney disease globally 41 . The GBD team estimated that in 2019, as many as 8% of deaths due to CKD were attributable to non-optimal (high or low) ambient temperatures 42 . For example, persistent exposure to high temperatures, particularly for agricultural and outdoor workers in LICs and LMICs who lack access to adaptation interventions, increase heat stress, which exacerbates the risk of kidney disease 43 , 44 , 45 , 46 . Heat stress is a potential contributor to CKD of unknown cause (CKDu) in agricultural communities, which is increasingly recognized as a major global cause of CKD. This condition is characterized by the presence of a benign urinary sediment and tubulointerstitial changes on biopsy 47 . Proposed mechanisms include recurrent heat stress with repeated episodes of AKI and exposure to environmental toxins, including pesticides and heavy metals 48 , 49 , 50 , 51 . Also known as CKD of non-traditional cause, chronic interstitial nephritis in agricultural communities, Mesoamerican nephropathy and Uddanam Nephropathy, CKDu has been observed largely in the Global South, including India, Sri Lanka, parts of Africa, and Central and South America 49 , 51 , 52 . One study of people with CKDu in India found worsening of metabolic acidosis and hypertension in summer compared with winter, supporting the hypothesis that a warming planet also threatens kidney health 50 . Increasing salinity of drinking water in coastal areas of Bangladesh affected by rising sea levels has also been linked to increased rates of preeclampsia and gestational hypertension, in addition to hypertension and albuminuria in the general population, all of which are risk factors for subsequent kidney disease 53 , 54 , 55 . Furthermore, large population studies suggest that rises in fine particulate matter in the air are associated with an increased risk of AKI, as well as CKD prevalence and progression 56 , 57 , 58 .

Climate change will also affect water availability. Since 2000, the global frequency and duration of drought have increased by nearly 30% 59 . In the context of profound drought, current haemodialysis options are not environmentally sustainable, as the average haemodialysis treatment uses >500 l of water 60 . Emergencies such as extreme climate events (drought, snowstorms, floods and fires), natural disasters such as the earthquakes in Turkey and Syria, and floods in Pakistan, as well as man-made disasters such as wars and conflicts, all impact the ability of patients with kidney disease to access and receive life-saving treatment such as haemodialysis or kidney transplantation, thereby endangering lives 61 , 62 , 63 . Notably, extreme events can also directly cause kidney injury, such as mass rhabdomyolysis from crush injuries caused by earthquakes 64 .

Threats to kidney health vary across the lifespan. In low-resource and underprivileged settings, maternal factors such as malnutrition, poor health literacy and comorbidity burden contribute to an adverse uterine environment 65 . Mothers in low-resource settings are more likely to give birth to children who are small for gestational age, have low birthweight or are born prematurely than those in high-resource settings 66 . Importantly, numerous large population studies show that small for gestational age, low birthweight and prematurity increase the risk that the infant might develop proteinuria, hypertension, CKD and kidney failure in later life 67 , 68 , 69 , 70 , 71 , 72 , 73 . This risk seems to be mediated through multiple mechanisms, with low nephron endowment owing to suboptimal growth in utero increasing susceptibility to kidney injury later in life 74 . Poor maternal nutrition, which, despite improvements, remains substantially prevalent in large parts of the world, also increases the risk of gestational diabetes and hypertension, both of which are known risk factors for CKD 65 . Poor infant and childhood nutrition, as well as childhood AKI events related to infections, superimpose additional layers of risk to kidney health across the lifespan 65 .

Although kidney diseases are commonly grouped with other NCDs, infections are also important causes of AKI in LICs and LMICs, either through direct kidney involvement (for example, in cases of leptospirosis or HIV infection) or indirectly through haemodynamic mechanisms, systemic inflammatory responses or infection-related glomerulonephritis 19 , 35 , 75 . The adverse kidney effects of infections in LICs and LMICs are exacerbated by decreased access to specialized care, especially in areas endemic for diseases such as malaria, leptospirosis, scrub typhus, haemorrhagic fevers or dengue, and in cases of severe gastrointestinal fluid loss 76 , 77 . AKI is associated with increased morbidity and mortality and affects all age groups, from neonates to older individuals. Continued high mortality due to childhood AKI in the absence of dialysis prompted the ISN to introduce the Saving Young Lives programme in collaboration with the International Society of Peritoneal Dialysis, European Peritoneal Dialysis, and the International Paediatric Nephrology Association to promote peritoneal dialysis in Africa, later expanded to Asia and Latin America 78 . However, this programme is just scratching the surface with regard to addressing the KRT needs of people with AKI in these regions.

Climate change and loss of global biodiversity are also increasing the risk of infectious diseases that predispose to AKI and CKD outside of current tropical areas as the climate becomes more conducive to the survival of parasites (for example, those causing malaria or schistosomiasis) and/or their vectors (for example, mosquitoes or ticks) 41 . Of note, although the association between certain infections and AKI is well known, the role of infections in the development and/or progression of CKD is not well studied. However, emerging data suggest that leptospirosis might contribute to the development of CKDu or increase susceptibility to triggers such as heat stress 79 , 80 , 81 .

Globally, multifactorial social determinants of health influence kidney health profoundly. Indigenous populations, people living in rural areas, migrants, older individuals or those affected by poverty, homelessness and food insecurity are more likely to be affected by kidney disease and develop its worst manifestations 36 , 37 , 38 , 82 , 83 . For example, underprivileged people with CKD are more likely to experience rapid progression of the disease 84 . Importantly, progressive CKD can also exacerbate poverty (see later discussion). Sex and gender further influence the causes of CKD, the profile of comorbidities and disease evolution over time 39 . These differences are probably driven by complex biological, social and system-level factors. For example, women are 29% more likely to have CKD than men, but men are more likely to die from CKD than women 7 , 85 . Notably, despite the increased competing risk of death, men are 47% more likely than women to access dialysis or have a kidney transplant 7 . In older general population cohorts, women had a lower baseline glomerular filtration rate (GFR), although men had a steeper rate of GFR decline over time 86 , 87 . This complex interplay of age, and sex or gender needs to be better understood to allow the development of appropriate health system-level responses.

Lack of health system response to kidney disease and global health

Despite being the third fastest-growing cause of death 13 , kidney disease has not received the attention it deserves from governments, multilateral organizations such as the WHO, the lay press or health systems. Failure to diagnose CKD is driven by the silent nature of the disease, as well as lack of awareness of the devastating consequences of opportunities missed owing to a lack of timely detection (including through coordinated screening programmes), referral to nephrologists and adequate management. Even when treatment is sought, the quality of care might be poor. Information asymmetry is evident in the lay press for kidney disease. In an analysis of US newspapers, kidney disease was 11-fold under-represented in the media as a discussed versus actual cause of death 88 . Diagnosis is further hampered by the limited availability or lack of tests needed to assess kidney function in many LICs or LMICs 89 .

Globally, health systems and governments have failed to create robust systems for generating data on the burden of kidney disease and its drivers. Data registries are vital for understanding disease epidemiology, tracking progress and developing cost-effective intervention targets. Kidney disease registries are sparse in LICs and LMICs, which is where they are most needed 90 . A 2022 review of dialysis registries found none in large Asian countries 91 . The African Association of Nephrology registry has been established in Africa, but so far only involves seven countries (Botswana, Burundi, Ghana, Kenya, Nigeria, South Africa and Zambia) 92 . Latin America is served by the Latin America Dialysis and Transplant Registry 93 . Of note, CKD registries are rare in both HICs and LICs.

Data from the 2023 Global Kidney Health Atlas revealed that the availability of national strategies to address CKD correlated positively with income level — LIC 11%, LMIC 23%, upper-middle-income countries 22% and HIC 33% 94 . Despite the immense health care costs, only 48% of national governments recognize CKD and/or its treatment and prevention as a health priority 94 . In 2016, 50% of countries had no national health system oversight of kidney care 95 . Even in HICs, coordinated multi-agency approaches are lacking 96 . For example, the 2022–2027 European Commission “Healthier Together — European Union Non-Communicable Diseases Initiative” does not address CKD 97 , 98 .

Targeting current WHO major NCDs will not solve the growing global kidney disease problem

CKD is often caused by pre-existing major NCDs that have been acknowledged by the WHO as priority conditions, such as diabetes, or by risk factors common to heart disease and stroke, such as hypertension. The WHO further reports that one-third of kidney mortality is caused by diabetic kidney disease 99 . However, glomerulonephritis, infection, malnutrition, environmental stressors and other toxins, pollution, climate change and obstetric catastrophes are all major causes of AKI and CKD that are not addressed in the current list of major NCDs. CKD of causes other than diabetes and hypertension already accounts for the highest global age-standardized rate of disability-adjusted life years (DALYs) 7 . Crucially, a common cause of kidney failure, even in HICs, is ‘kidney failure where the cause cannot be ascertained’. In a recent report of the European Renal Association, the cause of kidney failure was unknown in 28% of participants 100 . This finding emphasizes the need for research that can advance understanding of underlying causes of kidney disease and enable the development of cause-specific therapies. Failing to address kidney disease risk factors and mediators will fail to curb its devastating health, economic and psychosocial consequences.

Kidney diseases have multiple adverse consequences

Kidney disease causes premature mortality, disability, reduced quality of life and other psychosocial harms, and incurs high costs to governments, health care systems, and patients and their families (Box  1 ). The burden of this harm disproportionately affects those living in LICs and LMICs. Progressive CKD is a systemic disease and contributes to the evolution and progression of other major NCDs, most notably cardiovascular disease 101 .

Box 1 The burden of kidney disease

Premature mortality

Reduced quality of life

Psychosocial harm

High costs to governments and health care systems

High costs to individuals and families, in part because of lost productivity

Kidney disease carries high morbidity and mortality

The overall global age-standardized DALY rate declined sharply from 1990 to 2019 (ref. 102 ). In particular, the age-standardized DALY rate for WHO-recognized major NCDs such as ischaemic heart disease and stroke decreased by 28% and 35%, respectively 102 . By contrast, the age-standardized DALY rate for CKD increased by 6% (with an absolute increase of 62%) over the last 30 years, causing CKD to rise from the 29th to the 18th leading cause of global disability 102 , 103 . In 2017 alone, CKD resulted in 36 million DALYs 7 . Nearly 75% of DALYs occurred in countries within the lowest three sociodemographic index quintiles 7 . Current population demographic trajectories and the increase in kidney disease risk factors mean that, without urgent action, CKD will continue to rise through the league table of global causes of death and disability.

The symptom burden of CKD is profound, and patients with kidney failure experience a similar or greater symptom burden (including fatigue, itch and pain) than those with terminal malignancies 104 . Kidney disease has multiple adverse psychosocial consequences, including reduced quality of life, poor life participation and mental illness. A 2022 meta-analysis of nearly 200,000 patients demonstrated that CKD reduced quality of life, especially for those on dialysis, for whom the pooled 36-item Short Form Health Survey (SF-36) physical component summary score was 36 out of 100 (ref. 105 ). Even among patients who were not on KRT (that is, dialysis or transplantation), many reported a high symptom burden. At least 45% reported fatigue, poor mobility, bone and/or joint pain, drowsiness, insomnia and/or poor sleep, anxiety, pain, sexual dysfunction, muscle cramps, gastrointestinal distress, dyspnoea, itching, heartburn or oedema 105 . Children with CKD also have worse quality of life reported than those with type 1 diabetes or survivors of childhood cancer 106 . In older individuals, who typically have lower access to KRT than the younger adults, quality of life decreases and symptom burden increases for years before starting KRT and, in those starting KRT, symptom burden might stabilize but does not improve 107 , 108 , 109 . Of note, in advanced CKD, quality of life is worse in women than in men 107 . Moreover, having a person with CKD in the family adversely impacts the mental health of caregivers, 30–50% of whom report symptoms of anxiety or depression 110 , 111 , 112 , 113 .

The burden from kidney disease naturally extends to mortality. The global mortality from all kidney diseases likely ranges between 5 million and 11 million per year 114 and kidney dysfunction is currently the seventh leading risk factor for death 99 . AKI contributes to an estimated additional 1.7 million deaths per year 21 . Deaths due to kidney disease increased by 50% from 2000 to 2019, and even mild CKD increases the risk of morbidity and mortality 115 , 116 . In 2019, CKD in LICs led to ~600 YLL per age-standardized 100,000 population and around ~560 YLL per 100,000 in LMICs, compared with 200 YLL per 100,000 in HICs 102 . Increasing prevalence and the relatively young age at death mean that overall deaths and YLL due to kidney disease are predicted to escalate dramatically at a global level (Figs.  2 and 3 ). In 2040, kidney disease is predicted to cause 52 million YLL, moving from the 16th most common cause of YLL (in 2016) to the fifth, surpassing other major NCD drivers of early mortality listed by the WHO such as diabetes 14 (Fig.  3 ). In 2040, CKD is expected to account for 5% of YLL 14 , 18 (Fig.  4 ).

Modelling of Global Burden of Disease data reveals the global trend for an increase in predicted deaths due to chronic kidney disease (CKD) between 1990 and 2040. Data shown refers to CKD as cause of death for all ages and both sexes (deaths per 100,000). Data obtained from the Global Burden of Disease Foresight Visualization tool from the Institute for Health Metrics and Evaluation, University of Washington. Reprinted with permission from the Institute for Health Metrics and Evaluation.

Modelling of Global Burden of Disease data reveals the global trend for an increase in predicted years of life (YLL) lost because of chronic kidney disease (CKD) between 1990 and 2040. Data shown refer to chronic kidney disease (CKD) as cause of YLL for all ages and both sexes (YLL per 100,000). Data obtained from the Global Burden of Disease Foresight Visualization tool from the Institute for Health Metrics and Evaluation, University of Washington. Reprinted with permission from the Institute for Health Metrics and Evaluation.

Compared with data from 2016, the years of life lost (YLL) because of WHO-recognized major non-communicable diseases such as stroke and heart disease are predicted to have decreased by 2040. By contrast, YLL due to chronic kidney disease (CKD) are predicted to continue to increase and CKD is expected to surpass diabetes as a cause of YLL by 2040. Graph created using data from ref. 14 .

CKD also increases the risk of developing severe acute and chronic infections (such as COVID-19 and tuberculosis), which are major causes of death in LICs and LMICs 117 , 118 . Hence, decreasing the incidence and severity of CKD will have beneficial effects on other NCDs and communicable diseases.

Kidney disease increases the risk of other major NCDs

Beyond the directly attributable toll of kidney disease, CKD contributes to and exacerbates other major NCDs. Uraemic toxins and systemic inflammation have profound effects on other organ systems, and extensive kidney–heart, kidney–brain, and kidney–lung interactions underscore the high co-morbidity burden of CKD 119 , 120 , 121 . In 2017, the GBD study estimated that 1.4 million cardiovascular disease-related deaths and 25 million cardiovascular DALYs were lost owing to kidney disease 7 . Accordingly, the 2021 European Society of Cardiology cardiovascular disease prevention guidelines suggest screening people with CKD for atherosclerotic cardiovascular disease 122 . These guidelines also advocate for albuminuria screening in those with high cholesterol or diabetes, acknowledging the importance of CKD as a risk factor for cardiovascular disease 123 . Recognition of the role of CKD in increasing the risk of other major NCDs is essential to reducing overall NCD burden.

Kidney disease imposes unacceptably high costs on economies, health care systems and individuals

The direct health care costs of kidney disease are relevant at the global, country, health system and individual levels. Patients with CKD are complex to manage and account for a disproportionately large amount of national economic expenditure.

Most countries use a mix of public and private funding to provide kidney care. In 2016, only 19% of countries had completely publicly funded kidney care 95 . In the USA, kidney failure qualifies adults for Medicare benefits regardless of age. Of note, although <1% of Medicare beneficiaries have kidney failure, expenditures for kidney failure accounted for over 6% of Medicare spending in 2020, exceeding $50 billion 23 . US federal costs for people with CKD are >$85.4 billion annually, representing 23.5% of Medicare fee-for-service spending 23 . Similarly, in the UK, half of the National Health Service budget spent on CKD care went to those with kidney failure, who comprise only 2% of patients with CKD stages 3–5 (ref. 124 ). In a range of other HICs and MICs, 2–4% of the health care budget is spent on the 0.1–0.2% of the population with kidney failure 125 , 126 . Moreover, the costs of CKD care are rising given the increased prevalence of CKD and the complexity of patients with CKD. Inflation-adjusted spending in the USA on people with kidney failure in 2021 had increased 20% over the preceding decade 23 . Notably, US expenditure on people with CKD rose faster than that for the general population or even patients with diabetes or heart failure 23 . A large Canadian general population study also found that patients with kidney disease had the highest comorbidity burden, number of medications, death rate and need for placement in long-term care facilities 127 . In Europe, aggregated annual health care costs of CKD are estimated to be higher than those of cancer or diabetes mellitus 128 . The average length of hospital stay in the UK is 35% longer for people with CKD than for people without CKD 124 . Higher health care costs are also incurred from the increased rates of diseases such as cardiovascular disease in people with CKD. In the UK in 2010, a cost of £174 million was incurred from excess stroke and myocardial infarction in people with CKD 124 .

Health systems in LICs and LMICs will need increased funding to manage the rising burden of kidney disease. The prohibitive cost of dialysis likely explains the nearly 30-fold difference in the reported rates of kidney failure treated with dialysis between the country with the highest rate (Taiwan) and the country with the lowest rate (Bangladesh) 125 . In 2016, 40% of LIC and 22% of LMIC reported poor to extremely poor health care infrastructure for CKD care 95 . In Africa, where AKI is more common than in the rest of the world, 50% of countries reported poor to extremely poor AKI care infrastructure 95 . The negative impact of this lack of infrastructure is exacerbated by poor population coverage by nephrologists (0.2 nephrologists per million population in LICs, compared with 23 per million in HICs) 129 . For children, the situation is even more dire. In the 2018 Global Health Kidney Atlas, nearly 40% of LICs and LMICs reported absent or extremely limited access to a paediatric nephrologist 130 .

At the individual level, the costs of kidney care can be staggering. In LICs and LMICs the burden of meeting health care costs is largely placed on the individual. Only 13% of LICs and 19% of LMICs cover the cost of KRT for adults 95 . A World Bank report highlighted that out of all the disease groups, CKD is responsible for the largest number of people (188 million annually in LICs and LMICS) suffering catastrophic health care expenditures worldwide 131 . Even in the USA, where Medicare covers people with kidney failure, younger adults with CKD are not covered unless they have private health insurance, leading to massive out-of-pocket costs.

Kidney disease also has many indirect economic costs. The individual patient faces decreased earning potential, and educational and vocational outcomes are compromised in children with kidney disease 132 , 133 . In the USA, >75% of patients initiating dialysis were unemployed 134 . Caregivers face similar lost earning opportunities, and the state receives less taxation revenue.

With increasing prevalence, the overall global cost of providing kidney care is likely to rise. Moreover, with an ageing global population, the global tax base to fund health care will shrink over the next 30 years, emphasizing the crucial need to prevent kidney failure and its associated high health care costs (such as KRT costs) 135 . The recognition of kidney disease as a major global driver of mortality is, therefore, essential to focus efforts on improving kidney health and decreasing the massive health care costs associated with kidney disease.

The moral case for kidney health prioritization

It is unacceptable that the only NCD consistently witnessing an increase in the number of deaths year-on-year is not identified as a priority for policy action. Kidney diseases disproportionately affect the poor and disadvantaged, globally and within each country. Moreover, kidney disease not only has a profound negative impact on patients owing to its debilitating symptom burden but it also increases their risk of developing other major NCDs, restricts their ability to work and care for family members, and is cripplingly expensive for individuals, families, health systems and governments.

The changing population dynamics predicted over the next 20 years will translate to an increase in the number of people with kidney disease in LICs and LMICs, who are the least able to access kidney care. Arguments have been made that prioritizing kidney disease is not necessary in health systems without the resources to pay for the care of people with kidney disease. This approach will perpetuate and exacerbate the current global inequities in the care of patients with kidney disease, represents a pressing moral quandary to the world and is contrary to the Sustainable Development Agenda of leaving no one behind. Acceptance of such a situation by using the framing of cost-effectiveness as the primary metric further deprioritizes these patients, leading to the outright denial of care. The status quo perpetuates this injustice.

When kidney health care costs cannot be met, people die

Most people access care in community or secondary health care settings in LICs and LMICs. However, less than a third of LIC or LMIC community health care settings can access essential diagnostics such as those measuring kidney function (for example, estimated GFR and/or albuminuria testing) 136 . Medicines that can decrease albuminuria, or treat glomerulonephritis and the complications of CKD (such as anaemia or CKD–mineral and bone disorder) are crucial to slow disease progression and limit the burden of its complications (for example, cardiovascular disease) 137 , 138 . However, in a recent survey of the nephrology workforce in LICs and LMICs, only a third of respondents reported that essential kidney medicines (such as angiotensin-converting enzyme (ACE) inhibitors, anti-hypertensives, medications to treat acid–base and electrolyte disturbances or for CKD–mineral and bone disorder) were mostly available in community settings 139 . This finding highlights the avoidable progression to kidney failure and death faced by many patients in low-resource settings. Newer, paradigm-shifting medications, such as sodium–glucose cotransporter 2 (SGLT2) inhibitors and mineralocorticoid receptor antagonists are even less accessible.

Globally, <50% of all people requiring KRT can access it, with vast discrepancies in access between HICs and LICs 22 , 24 , 140 , 141 . Up to 98% of people with kidney failure in LICs do not receive KRT, compared with up to 30% in HICs. Of those patients unable to access KRT, 88% reside in Africa or Asia. The great disparity in wealth and availability of nephrologists greatly impact KRT funding and outcomes 142 . Approximately 93% of the world population receiving KRT lives in HICs or upper-middle-income countries, who comprise only 52% of the world population. Women, children, socially marginalized groups, migrants, and refugees are particularly disadvantaged 140 , 143 . Even those who access KRT often cease treatment quickly owing to cost constraints. In sub-Saharan Africa, only ~10% of adults and 35% of children who managed to access KRT were still on therapy by 3 months 144 . In a report from India that evaluated a state-funded dialysis programme, the number of patients accessing the service increased over time, but about two-thirds of patients discontinued dialysis in less than 1 year and likely died because they could not afford the substantial out-of-pocket payments needed to meet the indirect costs of care 126 .

Access to dialysis for AKI is similarly poor in LICs. Up to 85% of people with AKI live in the Global South 21 . In the ISN 0by25 global snapshot of AKI, nearly 50% of people who required dialysis in LICs and LMICs were unable to receive it owing to resource constraints or inability to pay 17 . A systematic review of AKI outcomes in sub-Saharan Africa found that only 64% of children and 33% of adults could access dialysis when needed 19 . In those unable to access dialysis, mortality was ~80% 19 .

Expected impact of placing kidney disease in the WHO list of NCD drivers of early death

The ISN, American Society of Nephrology and European Renal Association and nephrology communities worldwide unite in calling for kidney health to become a core part of the global health agenda. A crucial first step is the official recognition by the WHO that kidney disease is a major NCD driver of early mortality. The significance of prioritizing CKD by an important multilateral organization such as the WHO in strengthening the fight against CKD cannot be overstated. Specifically, prioritization by the WHO will help to raise awareness and demand for care, develop and implement guidelines and standards, improve implementation of locally appropriate surveillance and monitoring mechanisms, coordinate international efforts, and allocate resources more efficiently. In addition to enhanced efforts to prevent the development and progression of kidney disease, prioritization will foster investment towards the development of sorely needed new therapies (Box  2 ).

First, placing kidney disease on the WHO list of major NCD causes of premature mortality will enable a cohesive and targeted global campaign to decrease the harm caused by kidney disease, especially in emerging economies. Failure to spotlight kidney disease will undo or substantially slow progress towards the 2015 United Nations Sustainable Development Goal 3.4 of reducing premature mortality from NCDs by a third by 2030. Combating kidney disease will also contribute to action on many other SDGs, including SDG 1 (no poverty), 2 (gender equity), 6 (water security), 8 (work and economic growth), 10 (inequalities), and 13 (climate action). Adding kidney disease to the WHO major NCD list will translate to better health outcomes across the world and enhance the ability to address pervasive inequities that place disadvantaged populations at an increased risk of kidney disease.

Previous successful collaborations between the Latin American Society of Nephrology and Hypertension and the Pan American Health Organization, which is a specialized agency of the United Nations, exemplify the progress that can be made by multilateral organizational collaboration. This joint initiative has been pivotal in implementing and developing dialysis and transplantation registries, increasing knowledge of CKD and AKI among primary care health personnel, establishing a clinical and epidemiological definition of CKD of non-traditional causes, prioritizing individuals with kidney disease for COVID-19 vaccination, and establishing a direct line of action with local ministries of health 145 . The ongoing evolution of digital health technologies that can be leveraged to improve the detection and monitoring of kidney disease will accelerate these programmes and improve their implementation. Recognition of kidney disease as a major NCD driver of mortality is crucial to translating these gains to a global stage.

Early disease detection and a life course approach are cornerstones for reducing CKD-related morbidity and mortality worldwide. CKD meets the WHO principles for screening as the disease is asymptomatic in its early stages and effective early interventions are available 98 , 146 . In 2021, the Kidney Disease Improving Global Outcomes global multidisciplinary expert panel recommended screening high-risk groups (for example, individuals with diabetes or hypertension) for CKD 98 .

One of the main historical arguments against CKD screening has been the lack of effective therapies to slow disease progression, but this landscape has changed dramatically in the past 5 years. The advent of new therapeutic agents such as SGLT2 inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, endothelin receptor antagonists, selective mineralocorticoid receptor antagonists, and new glomerulonephritis-targeted therapies, means that early recognition of disease can translate into massive health improvements. For example, a 2021 meta-analysis revealed that SGLT2 inhibitor use decreased the risk of CKD progression by 37% in people with and without diabetes 128 . Consensus-based expert opinion recommends case detection in individuals with known risk factors such as diabetes, hypertension and cardiovascular disease 98 . As discussed above, the list of relevant risk factors is likely longer and poorly studied in LIC and LMICs 16 , 147 . Prioritization by the WHO will spur studies to more accurately document disease burden and risk factors in these geographic areas. Failure to identify people at a high risk of kidney disease development and/or progression is a missed opportunity to intervene and prevent kidney failure and its stratospheric health, economic and psychosocial costs 138 .

Prioritizing kidney disease will also facilitate the development and expansion of kidney disease registries. Accurate registry data are crucial to understanding trends and risk factors and to informing cost-effective and equitable resource delivery. The ISN, through its Share-RR program, is providing support for the setting up of registries, but such initiatives are unlikely to be sustainable without embedding in local health systems 148 . Registries are already highlighting global hotspots of kidney failure, enabling investigation of disease causes and improving the understanding of new disease entities such as CKDu 93 , 149 .

Greater attention to kidney health and disease will also translate into increased investment by governments, the private sector and research funders, which will spur innovation and new therapies. Despite spending disproportionate amounts of money on funding KRT, governments worldwide have not prioritized innovation in these areas. Professional societies have been trying to fill this gap, with exciting results. The Affordable Dialysis Prize co-funded by the ISN, the Asian Pacific Society of Nephrology, the Farrell Family Foundation and the George Institute for Global Health and has led to the development of a prototype of a low-cost dialysis machine . The KidneyX project in the USA is a public–private partnership that has raised tens of millions of dollars to foster innovations in dialysis care, including an artificial kidney prize .

New therapies that focus on the prevention of kidney disease development and progression will result in major health and socio-economic benefits. Finally, highlighting kidney disease will enable kidney health societies to expand advocacy for appropriate access to care for patients with kidney disease, increasing access to diagnosis and treatment and including medications needed to treat kidney disease in the WHO essential medicines list.

Shining a spotlight on kidney disease will not only result in decreased numbers of people needing resource-intensive kidney treatment but also empower programmes to reduce waste in dialysis. More sustainable dialysis modalities and technologies are urgently needed. Haemodialysis, the most common form of KRT, uses hundreds of litres of water per session 60 . In drought-affected areas, this demand poses a profound challenge. Decreasing the amount of people on dialysis by disease prevention will improve water security and reduce waste. Dialysis also produces >900,000 tonnes of plastic waste a year, rendering it one of the highest emitters of carbon emissions in health care 150 . In the USA, annual emissions per haemodialysis facility are estimated at nearly 770,000 kg of CO 2 equivalents 151 . Nearly 38,000,000 kg of recyclable plastic waste is generated annually from peritoneal dialysis globally, but limited recycling options exist 152 . Encouragingly, programmes to monitor electricity and water use in dialysis facilities have resulted in 30–50% savings, despite increasing patient numbers in France 153 .

Box 2 The impact of WHO recognition of CKD as a major driver of NCD-related early mortality

Rise in global awareness of CKD

Further development of guidelines and standards for the care of people with CKD

Improved implementation of locally appropriate surveillance and monitoring mechanisms

Facilitated coordination of international efforts to understand disease burden and develop evidence-based prevention approaches

Improved resource allocation

Fostering of investment for new therapies

Grand challenges for kidney health

Several major unmet policy, advocacy and implementation needs (Box  3 ) must be tackled to alleviate the global burden of kidney disease. We call for the global health community to address the following urgent public health needs to meet the needs of those at risk of, and with kidney diseases:

Improved access to care: Many people with CKD do not have access to adequate diagnostic and treatment (including preventive) services, particularly in LICs and LMICs. Similarly, >1 million people with potentially reversible AKI die yearly owing to lack of access to timely therapies, including dialysis. These gaps must be addressed by increasing the availability of affordable and accessible health care services.

Better prevention: More effective strategies are needed to prevent the development of CKD and AKI. Kidney disease risk factors need to be better understood, especially in LICs and LMICs, through appropriately designed studies using a multidisciplinary approach, interpreting the results in the context of the study population and its limitations, and considering their implications for the community and public health. In a recent White Paper, an ISN Working Group suggested points that countries should consider before developing a CKD case finding and management program, and put forward an evidence-based, resource-sensitive framework that can be adjusted to suit the local contexts. (139)

Developing, testing and scaling up novel balanced models of care: Implementing affordable, scalable and sustainable models of care requires co-development with stakeholder communities. Balanced models should also outline a systematic but flexible approach to planning treatment and care within the overall context of strengthened primary health care services. In low-resource settings, this approach might include a combination of task-sharing between physicians and non-physician health care workers in a locally appropriate way for diagnosis and follow-up care (facilitated by digital mobile technology and the use of clinical decision support systems with regional supervision), the use of online platforms to deliver competency training and facilitate supervision, and the use of peers for quality assurance. Potential risks of such approaches should be recognized and addressed by implementing policies that ensure the equitable delivery of safe, effective and high-quality care. In high-resource settings, care delivery needs to be refined across all levels of health care with the addition of an extended range of services in terms of coverage and degree of specialization.

Greater awareness and education: Many people with CKD are not aware that they have the disease, and many more are not aware of the steps that they can take to slow its progression. Similarly, a large proportion of the primary care community does not fully appreciate the adverse consequences of early-stage CKD. Greater awareness and education campaigns are needed to help people to understand the importance of early diagnosis and management of CKD.

Addressing social determinants of kidney health: As kidney diseases disproportionately affect impoverished and marginalized communities, addressing social determinants of health, such as poverty, poor housing and a lack of access to healthy food and clean water, is essential to address the burden of kidney diseases.

Increased funding for research and development: More funding is needed to support the development of new treatments and therapies for kidney diseases, and to improve understanding of these diseases and their underlying causes in different parts of the world.

International cooperation and coordination: To promote the development and implementation of effective policies and programmes for the prevention, early detection and management of kidney diseases, and to share knowledge and best practices, international cooperation and coordination are needed.

Greater engagement with patient communities: The demand for meaningful participation by community members in shaping health policies and in planning, delivering, quality assurance and evaluation of services has increased steadily. Greater engagement with patient communities is needed to ensure that policies and programmes address the needs and priorities of people living with kidney diseases effectively. Community involvement can range from consultation and collaboration to leadership.

Box 3 A path to developing sustainable patient-centred kidney care services to achieve Sustainable Development Goal targets

Improved access to care by integrating kidney care services into routine primary care and restructuring care pathways away from hospitals and into community settings

A staged approach to understanding and responding to kidney disease, with a focus on region-specific risk factors, comorbidity and multimorbidity

Task-sharing of integrated preventive, diagnostic and management interventions for kidney disease with non-specialized workers in the overall context of non-communicable disease care

Adoption of technological solutions, such as digital platforms and point of care tests, to facilitate the delivery of interventions across the continuum of care

Development of a continuum of the care pathway by integrating primary preventive care with specialist care

Commitment to involving patients and family members in planning and providing services

Implementation of community-based interventions to enhance the demand for preventive care

The 2015 United Nations Sustainable Development Goal 3.4 is aimed at reducing premature mortality from NCDs by a third by 2030. To tackle this goal, the WHO has recognized cancer, heart disease, stroke, chronic lung disease and diabetes as the major NCD drivers of early mortality. Failure to include kidney disease in this initiative misses the opportunity to address a major contributor to premature and preventable mortality. Changing population dynamics and evolving risk accumulation mean that the global burden of kidney disease is increasing relentlessly to become the fifth most common NCD driver of mortality by 2040. Kidney disease increases the risk of mortality, morbidity and disability, decreases quality of life and has profound individual- and health-system-level economic consequences, as well as dire environmental impacts. Kidney disease is under-recognized and under-resourced. Recognizing kidney disease as a major driver of NCD-related mortality will translate into coordinated global efforts to minimize the burden of kidney disease and will save lives.

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The authors thank representatives of the African Association of Nephrology (Abdou Niang and Hany Hafez), Asian Pacific Society of Nephrology (Sydney Tang), the International Diabetes Federation (Akthar Hussain), the International Society of Nephrology’s regional board chairs (Fatiu Arogundade, Muhammad Rafiqul Alam, Alejandro Ferreiro-Fuentes, Talerngsak Kanjanabuch, Kirill Komissarov, Jolanta Malyszko, Narayan Prasad, Larisa Prikhodina, Bassam Saeed, Maria José Soler Romeo, Carmen Tzanno-Martins, and Angela Wang), the Latin American Society of Nephrology and Hypertension (Guillermo Alvarez) and the World Heart Federation (Fausto Pinto) for reviewing and approving the manuscript before submission.

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Francis, A., Harhay, M.N., Ong, A.C.M. et al. Chronic kidney disease and the global public health agenda: an international consensus. Nat Rev Nephrol 20 , 473–485 (2024). https://doi.org/10.1038/s41581-024-00820-6

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NOAH WOUK, MD

Am Fam Physician. 2021;104(5):493-499

Patient information: See related handout on advanced kidney disease .

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End-stage renal disease (ESRD) is diagnosed when kidney function is no longer adequate for long-term survival without kidney transplantation or dialysis. Primary care clinicians should refer people at risk of ESRD to nephrology to optimize disease management. Kidney transplantation typically yields the best patient outcomes, although most patients are treated with dialysis. The decision to initiate dialysis is best made through shared decision-making. Because most patients with ESRD elect to receive hemodialysis, the preservation of peripheral veins is important for those with stage III to V chronic kidney disease. A palliative approach to ESRD is a reasonable alternative to dialysis, particularly for individuals with limited life expectancy, with severe comorbid conditions, or who wish to avoid medical interventions. For patients with ESRD, vaccination against seasonal influenza, tetanus, hepatitis B, human papillomavirus (through 26 years of age), and Streptococcus pneumoniae is advised. Routine cancer screening for patients not receiving kidney transplantation is discouraged. Controlling blood pressure in patients receiving dialysis improves mortality. Volume control through adequate dialysis and sodium restriction can help optimize hypertension treatment in these patients. Insulin is the preferred treatment for patients with ESRD and diabetes mellitus requiring medication. Patients should be monitored for signs of protein-energy wasting and malnutrition. Clinicians must be aware of the many medical complications associated with ESRD.

End-stage renal disease (ESRD) is when kidney function is no longer adequate for long-term survival without kidney transplantation or dialysis. 1 , 2 The estimated glomerular filtration rate (GFR) is usually less than 15 mL per minute per 1.73 m 2 when this occurs. 3 Kidney failure, a more concise term, may soon replace ESRD. 4

The incidence of ESRD increased more than threefold between 1980 and 2000 because of increasing numbers of patients with diabetes mellitus, hypertension, and related conditions. Although this increase has leveled off, the prevalence of ESRD has steadily increased, largely because of longer patient survival. By 2018, there were more than 750,000 individuals with ESRD in the United States. The disease is costly, accounting for approximately 10% of Medicare fee-for-service spending. It is also associated with high mortality; fewer than one-half of those who initiate hemodialysis survive for five years. 5

Primary care clinicians play a key role in diagnosing chronic kidney disease, monitoring its progression, treating modifiable risk factors, and identifying and treating complications. The evaluation of chronic kidney disease was discussed in a previous issue of American Family Physician ( AFP ). 6 ESRD often develops slowly and can be prevented in many cases. This article provides an overview of the medical management of ESRD, as well as its comorbidities and complications.

Nephrology Referral

Early nephrology referral for patients at increased risk of ESRD is vital because it is associated with improved patient-centered outcomes, including mortality. 3 , 7 Approximately one-third of all patients receive little to no nephrology care before ESRD is diagnosed. 5 , 8

Patients with chronic kidney disease should be referred to nephrology if their estimated GFR falls below 30 mL per minute per 1.73 m 2 . 3 A full list of indications for referral is provided in Table 1 . 3

Goals of early referral include initiating disease-specific therapies; slowing the progression of chronic kidney disease; evaluating and treating comorbid conditions and complications; providing psychosocial support; and planning for kidney transplantation, dialysis, or conservative kidney management. 3 Multidisciplinary care, involving primary care and other clinicians, pharmacists, nurses, dietitians, and social workers, may improve patient outcomes. 9

Kidney Transplantation

A key consideration for patients with ESRD is establishing eligibility for kidney transplantation, which, compared with dialysis or conservative management, improves survival and quality of life. 10 Referral to a transplantation program is advised when estimated GFR falls below 30 mL per minute per 1.73 m 2 because receiving a transplant before dialysis is needed improves survival. 11 Early referral allows time for medical and psychosocial evaluation, treatment of modifiable risk factors, and identification of a living donor; it also maximizes accrual of wait time on the transplant waiting list. 10 The median wait time for a transplant is four years, and currently only 5% of patients who initiate dialysis were preemptively placed on the kidney transplant waiting list. 5

Most patients elect to receive dialysis to treat their ESRD, 5 and these patients tend to live longer than those choosing conservative management. 12 Yet, because of the time commitment, discomfort, and complications associated with dialysis, shared decision-making should be used, with adequate time for patients to consider the various dialysis modalities and the option of conservative management. 3 Many patients do not receive adequate education before starting dialysis, and one survey showed that 61% of patients who chose dialysis later regretted the decision. 8

In the United States, nearly 90% of patients with ESRD are treated with center-based hemodialysis, but many patients are unaware that other options exist. 5 , 13 Alternatives include in-home hemodialysis and peritoneal dialysis, which can provide flexibility in frequency and duration of dialysis sessions. Patients who receive targeted education before the initiation of dialysis are more likely to choose peritoneal dialysis. 13 – 15

Alone, GFR does not determine when dialysis is initiated; instead, guidelines advise starting dialysis when irreversible signs or symptoms of ESRD manifest. 3 , 14 , 16 Common indications for dialysis include persistent volume overload; refractory metabolic disorders such as metabolic acidosis and hyperkalemia; cognitive impairment; and worsening nutritional status. 3 Table 2 lists indications for initiation of dialysis. 3 , 14

Most patients with ESRD will be treated with hemodialysis, and arteriovenous access (fistula or graft) is usually preferred. Early referral allows for evaluation and creation of vascular access before dialysis is needed. For patients with stage III to V chronic kidney disease, strategies to preserve peripheral venous access are important. These include avoiding excessive venipuncture, peripherally inserted central venous catheters, and subclavian venous catheters. 17 Once arteriovenous access is established, patients and clinicians should monitor the site for signs of infection, stenosis, and other complications (e.g., examining for tenderness, erythema, and swelling and confirming the presence of a palpable thrill). 18

Conservative Kidney Management

Patients with ESRD can elect a palliative approach to managing their disease that does not involve dialysis. This approach emphasizes quality of life over the prolongation of life. Although dialysis offers a survival benefit, that benefit decreases, and may disappear, with increasing patient age and comorbidity. 12 The overall symptom burden does not substantially improve in patients treated with dialysis, and they are more likely to receive medical interventions and to be hospitalized. 19 , 20 Conservative kidney management may be a reasonable alternative to dialysis, particularly for individuals with limited life expectancy or severe comorbid conditions and for those who strongly wish to avoid medical interventions. This topic was discussed further in a previous issue of AFP . 21

Other Considerations

Vaccination.

Because of immune suppression and increased susceptibility to infection in patients with ESRD, the Centers for Disease Control and Prevention (CDC) provides specific vaccination recommendations for this population. Routine vaccinations against seasonal influenza and tetanus should be continued in these patients. Additionally, the CDC recommends hepatitis B and pneumococcal vaccination (23-valent pneumococcal polysaccharide vaccine [Pneumovax-23] and 13-valent pneumococcal conjugate vaccine [Prevnar-13]). 22 , 23 The human papillomavirus vaccine should be offered to men and women through 26 years of age. 24 When vaccinating patients with ESRD against the herpes zoster virus, the recombinant vaccine (Shingrix) is preferred. 25 Chronic kidney disease is considered a risk factor for severe COVID-19, and vaccination is advised. 25 Updated vaccination guidance from the Advisory Committee on Immunization Practices can be found on the CDC website at https://www.cdc.gov/vaccines/hcp/acip-recs/index.html .

CANCER SCREENING

Given the limited life expectancy for most patients with ESRD who do not undergo kidney transplantation, routine cancer screening is discouraged in these patients. 17 , 26

People with ESRD are at high risk of developing protein-energy wasting and other malnutrition disorders and should receive nutritional counseling from a registered dietitian. Protein-energy wasting is strongly associated with increased mortality and other adverse outcomes. 27 , 28 Signs of protein-energy wasting include body mass index less than 23 kg per m 2 , unintentional weight loss (5% or more over three months or 10% or more over six months), and a serum albumin level less than 3.8 g per dL (38 g per L). 29 Although modest protein restriction may help prevent the progression of chronic kidney disease to ESRD, once ESRD develops, patients are typically counseled to consume a relatively high-protein diet (1.0 to 1.2 g of protein per kg of body weight per day). 28 Dietary protein supplements are often prescribed to patients with protein-energy wasting. Routine micronutrient supplementation is not necessary but should be considered when dietary intake is inadequate or signs or symptoms of specific micronutrient deficiencies are present. 28

HYPERTENSION

Most patients receiving dialysis have hypertension. Because blood pressure control is closely associated with volume status, modifying dialysis sessions to maintain normovolemia can improve blood pressure control. 30 , 31 Likewise, sodium restriction (less than 2 g per day) can reduce blood pressure by limiting fluid retention, but patient compliance is usually poor. 32

Blood pressure measurements provide more accurate prognostic information when obtained outside the dialysis setting (such as ambulatory or home blood pressure monitoring). 33 Antihypertensive therapy in patients receiving dialysis improves mortality, although target blood pressure values and the optimal first-line antihypertensive medications have not been established. 34

TYPE 2 DIABETES

Careful glucose monitoring in patients with ESRD and diabetes is important because insulin requirements are difficult to predict and the risk of hypoglycemia is increased in these patients. 35 Hyperglycemia may resolve when patients start dialysis. 36 The optimal A1C goal for patients with ESRD has not been established; however, maintaining an A1C between 6% and 9% may reduce mortality. 35 , 36 The accuracy and precision of A1C measurements are reduced in patients with ESRD, particularly when undergoing dialysis. Therefore, continuous glucose monitoring is a reasonable alternative, especially when there is substantial discordance between fasting glucose measurements and A1C measurements. 35

Insulin is preferred for most patients who require medication, although glipizide (Glucotrol) and repaglinide are acceptable oral alternatives. 37 When estimated GFR falls below 30 mL per minute per 1.73 m 2 , many diabetes medications, including metformin, are contraindicated. 37

Medical Complications of ESRD

Clinicians caring for patients with ESRD should be aware of its many complications. Patients with ESRD are at increased risk of bleeding due to platelet dysfunction, although dialysis may attenuate this risk. 38 Anemia (hemoglobin less than 13 g per dL [130 g per L] in men and less than 12 g per dL [120 g per L] in women) is common. Treatment includes intravenous iron for patients who are iron deficient and erythropoiesis-stimulating agents for select patients who are not iron deficient. 39 Patients who are not yet anemic should be monitored for anemia every three months. 39

Chronic metabolic acidosis is typically resolved with dialysis, but because the condition is associated with increased mortality and other adverse outcomes, those with persistently low bicarbonate concentrations (less than 22 mEq per L [22 mmol per L]) may require oral bicarbonate supplementation. 3 Potassium excretion by the kidneys is decreased in patients with ESRD, putting them at high risk of hyperkalemia and its complications. 40 Secondary hyperparathyroidism is also common; therefore, serum calcium and phosphate levels should be measured every one to three months, parathyroid hormone levels every three to six months, and alkaline phosphatase levels at least every 12 months. 41 Patients with ESRD should also be assessed for vitamin D deficiency. 41

Although rare, calciphylaxis is a life-threatening condition that may occur in patients with ESRD. The condition is characterized by small vessel occlusions in skin and adipose tissue that present as painful necrotic skin lesions. 42

Chronic kidney disease is considered a coronary heart disease risk equivalent, and patients with ESRD are at high risk of cardiovascular complications and death. 43 Although statin therapy can continue during dialysis treatments if already established, initiating statin therapy has not been shown to improve outcomes. 44 Aspirin is likely beneficial for individuals at very high risk of atherosclerotic events (e.g., those with recent myocardial infarction). However, there is a lack of conclusive evidence regarding the role of aspirin therapy for secondary prevention of cardiovascular disease in patients with ESRD. 45 , 46

Pericarditis is not uncommon in patients with ESRD and can manifest differently in this population. Patients with ESRD are more likely to present with constitutional symptoms, such as fever, chills, and malaise, and electrocardiography often does not show classic widespread ST elevations. 47

This article updates a previous article on this topic by O'Connor and Corcoran . 21

Data Sources: A PubMed search was completed in Clinical Queries using the key terms end-stage renal disease, end-stage kidney disease, and kidney failure. The search included meta-analyses, randomized controlled trials, and reviews. Also searched were the Agency for Healthcare Research and Quality Effective Healthcare Reports, the Cochrane database, and Essential Evidence Plus. Search date: October 3, 2020, and July 9, 2021.

Agarwal R. Defining end-stage renal disease in clinical trials: a framework for adjudication. Nephrol Dial Transplant. 2016;31(6):864-867.

End-stage renal disease (ESRD). Centers for Medicare and Medicaid Services. Accessed December 18, 2020. https://www.cms.gov/Medicare/Coordination-of-Benefits-and-Recovery/Coordination-of-Benefits-and-Recovery-Overview/End-Stage-Renal-Disease-ESRD/ESRD

• Levin A, Stevens PE, Bilous RW, et al. Kidney disease: improving global outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3(1):1-150.
• Levey AS, Eckardt K-U, Dorman NM, et al. Nomenclature for kidney function and disease: report of a Kidney Disease: Improving Global Outcomes (KDIGO) Consensus Conference. Kidney Int. 2020;97(6):1117-1129.

U.S. Renal Data System. 2020 annual data report. Accessed July 9, 2021. https://adr.usrds.org/2020

Gaitonde DY, Cook DL, Rivera IM. Chronic kidney disease: detection and evaluation. Am Fam Physician. 2017;96(12):776-783. Accessed July 3, 2021. https://www.aafp.org/afp/2017/1215/p776.html

• Smart NA, Dieberg G, Ladhani M, et al. Early referral to specialist nephrology services for preventing the progression to end-stage kidney disease. Cochrane Database Syst Rev. 2014;(6):CD007333.

Davison SN. End-of-life care preferences and needs: perceptions of patients with chronic kidney disease. Clin J Am Soc Nephrol. 2010;5(2):195-204.

U.S. Department of Veterans Affairs. VA/DoD clinical practice guidelines. Management of chronic kidney disease. 2019. Accessed July 9, 2021. https://www.healthquality.va.gov/guidelines/CD/ckd/

• Chadban SJ, Ahn C, Axelrod DA, et al. KDIGO clinical practice guideline on the evaluation and management of candidates for kidney transplantation. Transplantation. 2020;104(4S1 suppl 1):S11-S103.
• Ojo A, Wolfe RA, Agodoa LY, et al. Prognosis after primary renal transplant failure and the beneficial effects of repeat transplantation: multivariate analyses from the United States Renal Data System. Transplantation. 1998;66(12):1651-1659.
• Verberne WR, Geers ABMT, Jellema WT, et al. Comparative survival among older adults with advanced kidney disease managed conservatively versus with dialysis. Clin J Am Soc Nephrol. 2016;11(4):633-640.
• Kutner NG, Zhang R, Huang Y, et al. Patient awareness and initiation of peritoneal dialysis. Arch Intern Med. 2011;171(2):119-124.
• National Kidney Foundation. KDOQI clinical practice guideline for hemodialysis adequacy: 2015 update [published correction appears in Am J Kidney Dis . 2016;67(3):534]. Am J Kidney Dis. 2015;66(5):884-930.
• Devoe DJ, Wong B, James MT, et al. Patient education and peritoneal dialysis modality selection: a systematic review and meta-analysis. Am J Kidney Dis. 2016;68(3):422-433.
• Cooper BA, Branley P, Bulfone L, et al.; IDEAL Study. A randomized, controlled trial of early versus late initiation of dialysis. N Engl J Med. 2010;363(7):609-619.

Choosing Wisely five things physicians and patients should question. April 4, 2012. Accessed February 2, 2021. https://www.choosingwisely.org/choosing-wisely-five-things-physicians-and-patients-should-question-press-release-april-4-2012/

• Lok CE, Huber TS, Lee T, et al.; National Kidney Foundation. KDOQI clinical practice guideline for vascular access: 2019 update [published correction appears in Am J Kidney Dis . 2021;77(4):551]. Am J Kidney Dis. 2020;75(4 suppl 2):S1-S164.
• Wong SPY, Yu MK, Green PK, et al. End-of-life care for patients with advanced kidney disease in the US Veterans Affairs health care system, 2000–2011. Am J Kidney Dis. 2018;72(1):42-49.
• Tam-Tham H, Ravani P, Zhang J, et al. Association of Initiation of Dialysis With Hospital Length of Stay and Intensity of Care in Older Adults With Kidney Failure. JAMA Netw Open. 2020;3(2):e200222.

O'Connor NR, Corcoran AM. End-stage renal disease: symptom management and advance care planning [published correction appears in Am Fam Physician . 2012;85(10):950]. Am Fam Physician. 2012;85(7):705-710. Accessed July 3, 2021. https://www.aafp.org/afp/2012/0401/p705.html

• Schillie S, Vellozzi C, Reingold A, et al. Prevention of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67(1):1-31.
• Centers for Disease Control and Prevention. Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2012;61(40):816-819.

Petrosky E, Bocchini JA, Hariri S, et al.; Centers for Disease Control and Prevention. Use of 9-valent human papillomavirus (HPV) vaccine: updated HPV vaccination recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2015;64(11):300-304.

• Dooling K, Marin M, Wallace M, et al. The Advisory Committee on Immunization Practices' updated interim recommendation for allocation of COVID-19 vaccine - United States, December 2020. MMWR Morb Mortal Wkly Rep. 2021;69(5152):1657-1660.

Holley JL. Screening, diagnosis, and treatment of cancer in long-term dialysis patients. Clin J Am Soc Nephrol. 2007;2(3):604-610.

Kovesdy CP. Malnutrition in dialysis patients—the need for intervention despite uncertain benefits. Semin Dial. 2016;29(1):28-34.

• Ikizler TA, Burrowes JD, Byham-Gray LD, et al. KDOQI clinical practice guideline for nutrition in CKD: 2020 update [published correction appears in Am J Kidney Dis . 2021;77(2):308]. Am J Kidney Dis. 2020;76(3 suppl 1):S1-S107.
• Oliveira EA, Zheng R, Carter CE, et al. Cachexia/protein energy wasting syndrome in CKD: causation and treatment. Semin Dial. 2019;32(6):493-499.
• Agarwal R, Nissenson AR, Batlle D, et al. Prevalence, treatment, and control of hypertension in chronic hemodialysis patients in the United States. Am J Med. 2003;115(4):291-297.
• Argilés A, Lorho R, Servel M-F, et al. Seasonal modifications in blood pressure are mainly related to interdialytic body weight gain in dialysis patients. Kidney Int. 2004;65(5):1795-1801.

Ahmad S. Dietary sodium restriction for hypertension in dialysis patients. Semin Dial. 2004;17(4):284-287.

• Khan YH, Sarriff A, Adnan AS, et al. Blood pressure and mortality in hemodialysis patients: a systematic review of an ongoing debate. Ther Apher Dial. 2016;20(5):453-461.
• Heerspink HJL, Ninomiya T, Zoungas S, et al. Effect of lowering blood pressure on cardiovascular events and mortality in patients on dialysis: a systematic review and meta-analysis of randomised controlled trials. Lancet. 2009;373(9668):1009-1015.
• Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2020 clinical practice guideline for diabetes management in chronic kidney disease. Kidney Int. 2020;98(4S):S1-S115.
• Rhee CM, Leung AM, Kovesdy CP, et al. Updates on the management of diabetes in dialysis patients. Semin Dial. 2014;27(2):135-145.
• National Kidney Foundation. KDOQI clinical practice guideline for diabetes and CKD: 2012 update [published correction appears in Am J Kidney Dis . 2013;61(6):1049]. Am J Kidney Dis. 2012;60(5):850-886.
• Sohal AS, Gangji AS, Crowther MA, et al. Uremic bleeding: pathophysiology and clinical risk factors. Thromb Res. 2006;118(3):417-422.
• Mcmurray JJV, Parfrey PS, Adamson JW, et al.; Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work Group. KDIGO clinical practice guideline for anemia in chronic kidney disease. Kidney Int Suppl. 2012;2(4):279-335.

Ahmed J, Weisberg LS. Hyperkalemia in dialysis patients. Semin Dial. 2001;14(5):348-356.

• Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group. KDIGO 2017 clinical practice guideline update for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD) [published correction appears in Kidney Int Suppl (2011) . 2017;7(3):e1]. Kidney Int Suppl. 2017;7(1):1-59.

Nigwekar SU, Thadhani R, Brandenburg VM. Calciphylaxis. N Engl J Med. 2018;378(18):1704-1714.

• Sarnak MJ, Levey AS, Schoolwerth AC, et al. Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation. 2003;108(17):2154-2169.
• Kidney Disease: Improving Global Outcomes (KDIGO) Lipid Work Group. KDIGO Clinical Practice Guideline for Lipid Management in Chronic Kidney Disease. Kidney Int Suppl. 2013;3(3):259-305.
• Palmer SC, Di Micco LD, Razavian M, et al. Antiplatelet agents for chronic kidney disease. Cochrane Database Syst Rev. 2013;(2):CD008834.

K/DOQI Workgroup; K/DOQI clinical practice guidelines for cardiovascular disease in dialysis patients. Am J Kidney Dis. 2005;45(4 suppl 3):S1-S153.

Dad T, Sarnak MJ. Pericarditis and pericardial effusions in end-stage renal disease. Semin Dial. 2016;29(5):366-373.

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• End-stage renal disease

End-stage renal disease, also called end-stage kidney disease or kidney failure, occurs when chronic kidney disease — the gradual loss of kidney function — reaches an advanced state. In end-stage renal disease, your kidneys no longer work as they should to meet your body's needs.

Your kidneys filter wastes and excess fluids from your blood, which are then excreted in your urine. When your kidneys lose their filtering abilities, dangerous levels of fluid, electrolytes and wastes can build up in your body.

With end-stage renal disease, you need dialysis or a kidney transplant to stay alive. But you can also choose to opt for conservative care to manage your symptoms — aiming for the best quality of life during your remaining time.

How kidneys work

One of the important jobs of the kidneys is to clean the blood. As blood moves through the body, it picks up extra fluid, chemicals and waste. The kidneys separate this material from the blood. It's carried out of the body in urine. If the kidneys are unable to do this and the condition is untreated, serious health problems result, with eventual loss of life.

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Early in chronic kidney disease, you might have no signs or symptoms. As chronic kidney disease progresses to end-stage renal disease, signs and symptoms might include:

• Loss of appetite
• Fatigue and weakness
• Changes in how much you urinate
• Chest pain, if fluid builds up around the lining of the heart
• Shortness of breath, if fluid builds up in the lungs
• Swelling of feet and ankles
• High blood pressure (hypertension) that's difficult to control
• Difficulty sleeping
• Decreased mental sharpness
• Muscle twitches and cramps
• Persistent itching
• Metallic taste

Signs and symptoms of kidney disease are often nonspecific, meaning they can also be caused by other illnesses. Because your kidneys can make up for lost function, signs and symptoms might not appear until irreversible damage has occurred.

When to seek care

Make an appointment with your health care provider if you have signs or symptoms of kidney disease.

If you have a medical condition that increases your risk of kidney disease, your care provider is likely to monitor your kidney function with urine and blood tests and your blood pressure during regular office visits. Ask your provider whether these tests are necessary for you.

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Healthy kidney vs. diseased kidney

A typical kidney has about 1 million filtering units. Each unit, called a glomerulus, joins a tubule. The tubule collects urine. Conditions such as high blood pressure and diabetes harm kidney function by damaging these filtering units and tubules. The damage causes scarring.

Polycystic kidney

A healthy kidney (left) removes waste from the blood and maintains the body's chemical balance. With polycystic kidney disease (right), fluid-filled sacs called cysts develop in the kidneys. The kidneys grow larger and slowly lose their ability to work as they should.

Kidney disease occurs when a disease or condition impairs kidney function, causing kidney damage to worsen over several months or years. For some people, kidney damage can continue to progress even after the underlying condition is resolved.

Diseases and conditions that can lead to kidney disease include:

• Type 1 or type 2 diabetes
• High blood pressure
• Glomerulonephritis (gloe-mer-u-low-nuh-FRY-tis) — an inflammation of the kidney's filtering units (glomeruli)
• Interstitial nephritis (in-tur-STISH-ul nuh-FRY-tis), an inflammation of the kidney's tubules and surrounding structures
• Polycystic kidney disease or other inherited kidney diseases
• Prolonged obstruction of the urinary tract, from conditions such as enlarged prostate, kidney stones and some cancers
• Vesicoureteral (ves-ih-koe-yoo-REE-tur-ul) reflux, a condition that causes urine to back up into your kidneys
• Recurrent kidney infection, also called pyelonephritis (pie-uh-low-nuh-FRY-tis)

Risk factors

Certain factors increase the risk that chronic kidney disease will progress more quickly to end-stage renal disease, including:

• Diabetes with poor blood sugar control
• Kidney disease that affects the glomeruli, the structures in the kidneys that filter wastes from the blood
• Polycystic kidney disease
• Tobacco use
• Black, Hispanic, Asian, Pacific Islander or American Indian heritage
• Family history of kidney failure
• Frequent use of medications that could be damaging to the kidney

Complications

Kidney damage, once it occurs, can't be reversed. Potential complications can affect almost any part of your body and can include:

• Fluid retention, which could lead to swelling in your arms and legs, high blood pressure, or fluid in your lungs (pulmonary edema)
• A sudden rise in potassium levels in your blood (hyperkalemia), which could impair your heart's ability to function and may be life-threatening
• Heart disease
• Weak bones and an increased risk of bone fractures
• Decreased sex drive, erectile dysfunction or reduced fertility
• Damage to your central nervous system, which can cause difficulty concentrating, personality changes or seizures
• Decreased immune response, which makes you more vulnerable to infection
• Pericarditis, an inflammation of the saclike membrane that envelops your heart (pericardium)
• Pregnancy complications that carry risks for the mother and the developing fetus
• Malnutrition
• Irreversible damage to your kidneys (end-stage kidney disease), eventually requiring either dialysis or a kidney transplant for survival

If you have kidney disease, you may be able to slow its progress by making healthy lifestyle choices:

• Achieve and maintain a healthy weight
• Be active most days
• Limit protein and eat a balanced diet of nutritious, low-sodium foods
• Control your blood pressure
• Take your medications as prescribed
• Have your cholesterol levels checked every year
• Control your blood sugar level
• Don't smoke or use tobacco products
• Get regular checkups

End-stage renal disease care at Mayo Clinic

• Goldman L, et al., eds. Chronic kidney disease. In: Goldman-Cecil Medicine. 26th ed. Elsevier; 2020. http://www.clinicalkey.com. Accessed April 27, 2021.
• Chronic kidney disease (CKD). National Institute of Diabetes and Digestive and Kidney Diseases. https://www.niddk.nih.gov/health-information/kidney-disease/chronic-kidney-disease-ckd#:~:text=Chronic%20kidney%20disease%20(CKD)%20means,family%20history%20of%20kidney%20failure. Accessed April 26, 2021.
• Rosenberg M. Overview of the management of chronic kidney disease in adults. https://www.uptodate.com/contents/search. Accessed April 26, 2021.
• Chronic kidney disease. Merck Manual Professional Version. https://www.merckmanuals.com/professional/genitourinary-disorders/chronic-kidney-disease/chronic-kidney-disease?query=Chronic%20kidney%20disease. Accessed April 26, 2021.
• Office of Patient Education. Chronic kidney disease treatment options. Mayo Clinic; 2020.
• Are you at increased risk for chronic kidney disease (CKD)? National Kidney Foundation. https://www.kidney.org/atoz/content/atriskckd. Accessed May 25, 2021.
• Warner KJ. Allscripts EPSi. Mayo Clinic. April 12, 2021.
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Optimizing outcomes in the elderly with end-stage renal disease--live long and prosper

Affiliations.

• 1 Regional Nephrology Unit, Belfast City Hospital, Belfast, Northern Ireland - UK.
• 2 Nephrology Research Group, Centre for Public Health, Queen's University Belfast, Royal Victoria Hospital, Belfast, Northern Ireland - UK.
• PMID: 26109536
• DOI: 10.5301/jva.5000440

Background: The elderly form an expanding proportion of patients with chronic kidney disease and end-stage renal disease worldwide. The increased physiological frailty and functional morbidity associated with the aging process pose unique challenges when planning optimal management of an older patient needing renal replacement therapy (RRT).

Aims: This position paper discusses current evidence regarding the optimal management of end-stage renal disease in the elderly with an emphasis on hemodialysis since it is the most common modality used in older patients. Further research is needed to define relevant patient-reported outcome measures for end-stage renal disease including functional assessments and psychological impacts of various forms of RRT. For those older patients who have opted for dialysis treatment, it is important to study the strategies that encourage greater uptake of home-based dialysis therapies and optimal vascular access.

Conclusions: The management of advanced chronic kidney disease in the elderly can be challenging but also extremely rewarding. The key issue is adopting a patient-focused and individualized approach that seeks to achieve the best outcomes based on a comprehensive holistic assessment of what is important to the patient.

PubMed Disclaimer

• Optimizing vascular access in the elderly: words we use affect patient care. Davidson I, Gallieni M. Davidson I, et al. J Vasc Access. 2015 Nov-Dec;16(6):437-8. doi: 10.5301/jva.5000466. Epub 2015 Sep 8. J Vasc Access. 2015. PMID: 26349884

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• Dialysis therapies in older patients with end-stage renal disease. Malavade T, Sokwala A, Jassal SV. Malavade T, et al. Clin Geriatr Med. 2013 Aug;29(3):625-39. doi: 10.1016/j.cger.2013.05.005. Clin Geriatr Med. 2013. PMID: 23849012
• Hemodialysis vascular access in the elderly-getting it right. Viecelli AK, Lok CE. Viecelli AK, et al. Kidney Int. 2019 Jan;95(1):38-49. doi: 10.1016/j.kint.2018.09.016. Kidney Int. 2019. PMID: 30606427 Review.
• End-Stage Kidney Disease in the Elderly: Approach to Dialysis Initiation, Choosing Modality, and Predicting Outcomes. Berger JR, Jaikaransingh V, Hedayati SS. Berger JR, et al. Adv Chronic Kidney Dis. 2016 Jan;23(1):36-43. doi: 10.1053/j.ackd.2015.08.005. Adv Chronic Kidney Dis. 2016. PMID: 26709061 Review.
• Dialysis initiation, modality choice, access, and prescription: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Chan CT, Blankestijn PJ, Dember LM, Gallieni M, Harris DCH, Lok CE, Mehrotra R, Stevens PE, Wang AY, Cheung M, Wheeler DC, Winkelmayer WC, Pollock CA; Conference Participants. Chan CT, et al. Kidney Int. 2019 Jul;96(1):37-47. doi: 10.1016/j.kint.2019.01.017. Epub 2019 Apr 13. Kidney Int. 2019. PMID: 30987837
• Quality Measures for Dialysis: Time for a Balanced Scorecard. Kliger AS. Kliger AS. Clin J Am Soc Nephrol. 2016 Feb 5;11(2):363-8. doi: 10.2215/CJN.06010615. Epub 2015 Aug 27. Clin J Am Soc Nephrol. 2016. PMID: 26316622 Free PMC article. Review.
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Chronic Kidney Disease Diagnosis and Management

Author Contributions: Dr Grams had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Acquisition, analysis, or interpretation of data: Chen, Grams.

Drafting of the manuscript: Chen.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Grams.

Administrative, technical, or material support: Chen, Knicely.

Supervision: Grams.

Additional Contributions: We thank Andrew S. Levey, MD, Tufts Medical Center, and Natalie Daya, MS, Johns Hopkins University, for helpful input on the manuscript (uncompensated).

Chronic kidney disease (CKD) is the 16th leading cause of years of life lost worldwide. Appropriate screening, diagnosis, and management by primary care clinicians are necessary to prevent adverse CKD-associated outcomes, including cardiovascular disease, end-stage kidney disease, and death.

OBSERVATIONS

Defined as a persistent abnormality in kidney structure or function (eg, glomerular filtration rate [GFR] <60 mL/min/1.73 m 2 or albuminuria ≥30 mg per 24 hours) for more than 3 months, CKD affects 8% to 16% of the population worldwide. In developed countries, CKD is most commonly attributed to diabetes and hypertension. However, less than 5% of patients with early CKD report awareness of their disease. Among individuals diagnosed as having CKD, staging and new risk assessment tools that incorporate GFR and albuminuria can help guide treatment, monitoring, and referral strategies. Optimal management of CKD includes cardiovascular risk reduction (eg, statins and blood pressure management), treatment of albuminuria (eg, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers), avoidance of potential nephrotoxins (eg, nonsteroidal anti-inflammatory drugs), and adjustments to drug dosing (eg, many antibiotics and oral hypoglycemic agents). Patients also require monitoring for complications of CKD, such as hyperkalemia, metabolic acidosis, hyperphosphatemia, vitamin D deficiency, secondary hyperparathyroidism, and anemia. Those at high risk of CKD progression (eg, estimated GFR <30 mL/min/1.73 m 2 , albuminuria ≥300 mg per 24 hours, or rapid decline in estimated GFR) should be promptly referred to a nephrologist.

CONCLUSIONS AND RELEVANCE

Diagnosis, staging, and appropriate referral of CKD by primary care clinicians are important in reducing the burden of CKD worldwide.

Chronic kidney disease (CKD) affects between 8% and 16% of the population worldwide and is often underrecognized by patients and clinicians. 1 – 4 Defined by a glomerular filtration rate (GFR) of less than 60 mL/min/1.73 m 2 , albuminuria of at least 30 mg per 24 hours, or markers of kidney damage (eg, hematuria or structural abnormalities such as polycystic or dysplastic kidneys) persisting for more than 3 months, 5 CKD is more prevalent in low- and middle-income than in high-income countries. 6 Globally, CKD is most commonly attributed to diabetes and/or hypertension, but other causes such as glomerulonephritis, infection, and environmental exposures (such as air pollution, herbal remedies, and pesticides) are common in Asia, sub-Saharan Africa, and many developing countries. 4 Genetic risk factors may also contribute to CKD risk. For example, sickle cell trait and the presence of 2 APOL1 risk alleles, both common in people of African ancestry but not European ancestry, may double the risk of CKD. 4 , 7 – 10

In the United States, the average rate of GFR decline is approximately 1 mL/min/1.73 m 2 per year in the general population, 11 , 12 and the lifetime risk of developing a GFR of less than 60 mL/min/1.73 m 2 is more than 50%. 13 Early detection and treatment by primary care clinicians is important because progressive CKD is associated with adverse clinical outcomes, including end-stage kidney disease (ESKD), cardiovascular disease, and increased mortality. 14 – 17 Recent professional guidelines suggest a risk-based approach to the evaluation and management of CKD. 5 , 18 – 20 This review includes discussion of new calculators for determining risk of CKD progression that may be useful in clinical practice (eg, https://kidneyfailurerisk.com/ ) and focuses on the diagnosis, evaluation, and management of CKD for primary care clinicians. Considerations for referral to a nephrologist and dialysis initiation are also covered.

A literature search to April 2019 was conducted using Medline and PubMed with search terms including CKD , chronic renal failure , chronic renal insufficiency , epidemiology , incidence , prevalence , occurrence , diagnosis , assessment , identification , screening , workup , etiology , causes , management , treatment , intervention , therapy , and prevention . Results were restricted to English-language, human studies, and academic journals and guidelines. The initial search resulted in 998 articles, including clinical trials, meta-analyses, practice guidelines, and systematic reviews, and was later expanded to include review articles and observational studies, including cross-sectional studies, and more recent publications contained in reference lists of identified articles. All clinical trials for treatment or prevention of CKD were included without regard to study size or age of patient population.

Clinical Presentation

Chronic kidney disease is typically identified through routine screening with serum chemistry profile and urine studies or as an incidental finding. Less commonly, patients may present with symptoms such as gross hematuria, “foamy urine” (a sign of albuminuria), nocturia, flank pain, or decreased urine output. If CKD is advanced, patients may report fatigue, poor appetite, nausea, vomiting, metallic taste, unintentional weight loss, pruritus, changes in mental status, dyspnea, or peripheral edema. 21

In evaluating a patient with known or suspected CKD, clinicians should inquire about additional symptoms that might suggest a systemic cause (eg, hemoptysis, rash, lymphadenopathy, hearing loss, neuropathy) or urinary obstruction (eg, urinary hesitancy, urgency, or frequency or incomplete bladder emptying). 21 Moreover, patients should be assessed for risk factors of kidney disease, including prior exposure to potential nephrotoxins (eg, nonsteroidal anti-inflammatory drugs [NSAIDs], phosphate-based bowel preparations, herbal remedies such as those containing aristolochic acid, antibiotic therapies such as gentamicin, and chemotherapies), history of nephrolithiasis or recurrent urinary tract infections, presence of comorbidities (eg, hypertension, diabetes, autoimmune disease, chronic infections), family history of kidney disease, and, if available, other known genetic risk factors such as sickle cell trait. 9 , 18 , 21 – 24

A detailed physical examination may provide additional clues regarding the underlying cause of CKD and should include careful evaluation of a patient’s volume status. Signs of volume depletion may reflect poor oral intake, vomiting, diarrhea, or overdiuresis, whereas signs of volume overload may be due to decompensated heart failure, liver failure, or nephrotic syndrome. The presence of arterial-venous nicking or retinopathy on retinal examination suggests long-standing hypertension or diabetes. Patients with carotid or abdominal bruits may have renovascular disease. Flank pain or enlarged kidneys should prompt consideration of obstructive uropathy, nephrolithiasis, pyelonephritis, or polycystic kidney disease. Neuropathy may be due to diabetes or less commonly vasculitis, or amyloidosis. Skin findings may include rash (systemic lupus erythematosus, acute interstitial nephritis), palpable purpura (Henoch-Schonlein purpura, cryoglobulinemia, vasculitis), telangiectasias (scleroderma, Fabry disease), or extensive sclerosis (scleroderma). Patients with advanced CKD may exhibit pallor, skin excoriations, muscle wasting, asterixis, myoclonic jerks, altered mental status, and pericardial rub. 21

CKD Definition and Staging

Chronic kidney disease is defined as the presence of an abnormality in kidney structure or function persisting for more than 3 months. 5 , 25 This includes 1 or more of the following: (1) GFR less than 60 mL/min/1.73 m 2 ; (2) albuminuria (ie, urine albumin ≥30 mg per 24 hours or urine albumin-to-creatinine ratio [ACR] ≥30 mg/g); (3) abnormalities in urine sediment, histology, or imaging suggestive of kidney damage; (4) renal tubular disorders; or (5) history of kidney transplantation. 5 If the duration of kidney disease is unclear, repeat assessments should be performed to distinguish CKD from acute kidney injury (change in kidney function occurring within 2–7 days) and acute kidney disease (kidney damage or decreased kidney function present for ≤3 months). 25 Evaluation for the etiology of CKD should be guided by a patient’s clinical history, physical examination, and urinary findings ( Figure 1 ). 5 , 18 , 21

a Other imaging modalities or urine studies may also be considered.

b A variety of scores are available, eg, https://kidneyfailurerisk.com/ .

Once a diagnosis of CKD has been made, the next step is to determine staging, which is based on GFR, albuminuria, and cause of CKD ( Figure 2 ). 5 Staging of GFR is classified as G1 (GFR ≥90 mL/min/1.73 m 2 ), G2 (GFR 60–89 mL/min/1.73 m 2 ), G3a (45–59 mL/min/1.73 m 2 ), G3b (30–44 mL/min/1.73 m 2 ), G4 (15–29 mL/min/1.73 m 2 ), and G5 (<15 mL/min/1.73 m 2 ). 5 Although GFR can be directly measured by clearance of agents such as iohexol or iothalamate, 26 – 28 the development of estimating equations (eg, the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] and Modification of Diet in Renal Disease Study [MDRD] equations) has largely replaced the need for direct measurement in clinical practice. 29 – 31 Clinical laboratories now routinely report estimated GFR (eGFR) based on filtration markers. The most common filtration marker used is creatinine, a 113 dalton byproduct of creatine metabolism 25 and one for which laboratory assays have been standardized since 2003. 32 The preferred estimating equation in the United States and much of the world is the CKD-EPI 2009 creatinine equation, which is more accurate than the earlier MDRD equation, particularly for eGFR values greater than 60 mL/min/1.73 m 2 ( https://www.kidney.org/professionals/kdoqi/gfr_calculator). 29 , 30 In situations requiring additional accuracy and precision, cystatin C can be used with creatinine in the CKD-EPI 2012 creatinine-cystatin C equation. 31 Adding cystatin C may be particularly useful for individuals with altered creatinine production and/or metabolism (eg, extremely high or low body size or muscle mass, limb amputation, high-protein diet, use of creatinine supplements, or use of drugs affecting tubular secretion of creatinine). 5 , 25

GFR indicates glomerular filtration rate; KDIGO, Kidney Disease Improving Global Outcomes. Categories are grouped by risk of progression, which includes chronic kidney disease progression, defined by a decline in GFR category (accompanied by a ≥25% decrease in estimated GFR from baseline) or sustained decline in estimated GFR greater than 5 mL/min/1.73 m 2 per year. Green indicates low risk (if no other markers of kidney disease and no CKD); yellow, moderately increased risk; orange: high risk; and red, very high risk. Reproduced with permission from Kidney International Supplements . 5

Albuminuria should ideally be quantified by a urine ACR. Albuminuria staging is classified as A1 (urine ACR <30 mg/g), A2 (30–300 mg/g), and A3 (>300 mg/g). 5 Guidelines recommend the use of urine ACR to stage CKD rather than urine protein-to-creatinine ratio because assays for the former are more likely to be standardized and have better precision at lower values of albuminuria. 5 , 33 The most precise measurements come from a first morning sample or 24-hour collection, as there is high biological variability in urine albumin excretion over the course of the day. 5 , 34 , 35 Random samples, however, are also acceptable in initial screening. 5 Compared with urine protein-to-creatinine ratio, urine ACR is believed to be a more sensitive and specific marker of glomerular pathology 5 since some urine proteins such as uromodulin are present (and may even be protective) in normal physiology. 36 – 38 If tubular or overflow proteinuria is suspected, then urine protein electrophoresis or testing for the specific protein can be pursued (eg, immunoglobulin heavy and light chains, α 1 -microglobulin, and β 2 -microglobulin). 5 Imaging by kidney ultrasound to assess morphology and to rule out urinary obstruction should be considered in all patients diagnosed as having CKD. 5

Cause of CKD can be difficult to discern but is generally classified by the presence or absence of systemic disease and the location of anatomic abnormality. Examples of systemic disease include diabetes, autoimmune disorders, chronic infection, malignancy, and genetic disorders in which the kidney is not the only organ affected. Anatomic locations are divided into glomerular, tubulointerstitial, vascular, and cystic/congenital diseases. 5 Determining the cause of CKD may have important implications on prognosis and treatment. For example, polycystic kidney disease may progress to ESKD faster than other causes and often requires evaluation for extrarenal manifestations and consideration of specific therapies such as tolvaptan, a vasopressin V2 receptor antagonist that slows decline in GFR. 39 , 40 Patients with unexplained causes of CKD should be referred to a nephrologist.

Screening for CKD

Given that most patients with CKD are asymptomatic, screening may be important to early detection of disease. 18 The National Kidney Foundation has developed a kidney profile test that includes measuring both serum creatinine for estimating GFR and urine ACR. 41 A risk-based approach to screening is suggested by many clinical practice guidelines, with screening recommended in those older than 60 years or with a history of diabetes or hypertension. 18 – 20 Screening should also be considered in those with clinical risk factors, including autoimmune disease, obesity, kidney stones, recurrent urinary tract infections, reduced kidney mass, exposure to certain medications such as NSAIDs or lithium, and prior episodes of acute kidney injury, among others ( Box ). 9 , 18 , 42 – 45 However, no randomized clinical trials have demonstrated that screening asymptomatic patients for CKD improves outcomes.

Clinical, Sociodemographic, and Genetic Risk Factors for Chronic Kidney Disease

Hypertension

Autoimmune diseases

Systemic infections (eg, HIV, hepatitis B virus, hepatitis C virus)

Nephrotoxic medications (eg, nonsteroidal anti-inflammatory drugs, herbal remedies, lithium)

Recurrent urinary tract infections

Kidney stones

Urinary tract obstruction

Reduced kidney mass (eg, nephrectomy, low birth weight)

History of acute kidney injury

Intravenous drug use (eg, heroin, cocaine)

Family history of kidney disease

Sociodemographic

Age >60 years

Nonwhite race

Low education

APOL1 risk alleles

Sickle cell trait and disease

Polycystic kidney disease

Alport syndrome

Congenital anomalies of the kidney and urinary tract

Other familial causes

Other Risk Factors for CKD

There are several sociodemographic factors that contribute to increased risk of CKD, including nonwhite race, low education, low income, and food insecurity. 18 , 43 , 46 Compared with whites, African Americans and Pacific Islanders have a substantially greater risk of ESKD. 47 This is in part due to an increased prevalence of hypertension, diabetes, and obesity. 11 However, genetic factors likely also contribute. More specifically, risk alleles in the gene encoding apolipoprotein L1 ( APOL1 ) may increase risk of kidney disease in a recessive genetic manner 7 , 8 : individuals with 2 APOL1 risk alleles (present in approximately 13% of African Americans) have a 2-fold risk of CKD progression and up to a 29-fold risk of specific CKD etiologies (eg, focal-segmental glomerulosclerosis and HIV-associated nephropathy) compared with those with 0 or 1 risk allele. 11 , 44 , 45 , 48 , 49 Sickle cell trait (present in approximately 8% of African Americans) has also been associated with an increased risk of kidney disease. Compared with noncarriers, individuals with sickle cell trait have a 1.8-fold odds of incident CKD, 1.3-fold odds of eGFR decline greater than 3 mL/min/1.73 m 2 , and 1.9-fold odds of albuminuria. 9

Management of Patients With CKD

Reducing risk of cardiovascular disease.

The prevalence of cardiovascular disease is markedly higher among individuals with CKD compared with those without CKD. For example, in a Medicare 5% sample, 65% of the 175 840 adults aged 66 years or older with CKD had cardiovascular disease compared with 32% of the 1 086 232 without CKD. 47 Moreover, presence of CKD is associated with worse cardiovascular outcomes. For example, in the same population, the presence of CKD was associated with lower 2-year survival in people with coronary artery disease (77% vs 87%), acute myocardial infarction (69% vs 82%), heart failure (65% vs 76%), atrial fibrillation (70% vs 83%), and cerebrovascular accident/transient ischemic attack (73% vs 83%). 47

Therefore, a major component of CKD management is reduction of cardiovascular risk. It is recommended that patients aged 50 years or older with CKD be treated with a low- to moderate-dose statin regardless of low-density lipoprotein cholesterol level. 50 – 52 Smoking cessation should also be encouraged. 5 , 53 Both the Eighth Joint National Committee (JNC 8) and Kidney Disease: Improving Global Outcomes (KDIGO) guidelines have recommended goal systolic and diastolic blood pressures of less than 140 mm Hg and less than 90 mm Hg, respectively, among adults with CKD based on expert opinion. 5 , 54 The KDIGO guidelines further recommend that adults with urine ACR of at least 30 mg per 24 hours (or equivalent) have systolic and diastolic blood pressures maintained below 130 mm Hg and 80 mm Hg, respectively. 5 More recently, the Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated that among individuals with increased risk of cardiovascular disease but without diabetes, more intensive blood pressure control (goal systolic blood pressure <120 mm Hg) was associated with a 25% lower (1.65% vs 2.19% per year) risk of a major cardiovascular event and a 27% lower risk of all-cause mortality compared with standard blood pressure control (goal systolic blood pressure <140 mm Hg). 55 The intensive treatment group had a greater risk of at least a 30% decline in eGFR to a level below 60 mL/min/1.73 m 2 ; however, this may have been due to hemodynamic changes rather than true kidney function loss. 55 , 56 Importantly, the benefits of intensive blood pressure control on cardiovascular events were similar in participants with and without baseline CKD. 57

Management of Hypertension

Many guidelines provide algorithms detailing which agents should be used to treat hypertension in people with CKD. 54 , 58 Presence and severity of albuminuria should be evaluated. Blockade of the renin-angiotensin-aldosterone system with either an angiotensin-converting enzyme inhibitor (ACE-I) or an angiotensin II receptor blocker (ARB) is recommended for adults with diabetes and a urine ACR of at least 30 mg per 24 hours or any adult with a urine ACR of at least 300 mg per 24 hours. 5 , 18 , 58 Dual therapy with an ACE-I and an ARB is generally avoided, given associated risks of hyperkalemia and acute kidney injury. 5 , 18 , 59 Aldosterone receptor antagonists may also be considered in patients with albuminuria, resistant hypertension, or heart failure with reduced ejection fraction. 58 , 60 – 64

Management of Diabetes Mellitus

Optimal management of diabetes is also important. First, glycemic control may delay progression of CKD, with most guidelines recommending a goal hemoglobin A1c of ~ 7.0%. 5 , 18 , 19 , 65 – 67 Second, dose adjustments in oral hypoglycemic agents may be necessary. In general, drugs that are largely cleared by the kidneys (eg, glyburide) should be avoided, whereas drugs metabolized by the liver and/or partially excreted by the kidneys (eg, metformin and some dipeptidyl peptidase 4 [DPP-4] and sodium-glucose cotransporter-2 [SGLT-2] inhibitors) may require dose reduction or discontinuation, particularly when eGFR falls below 30 mL/min/1.73 m 2 . 18 , 19 Third, use of specific medication classes such as SGLT-2 inhibitors in those with severely increased albuminuria should be considered. The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial demonstrated that, among 4401 patients with type 2 diabetes and CKD stage G2-G3/A3 (baseline eGFR 30 to <90 mL/min/1.73 m 2 and urine ACR>300 to 5000 mg/24 hours) taking ACE-I or ARB therapy, those randomized to canagliflozin had a 30% lower risk (43.2 vs 61.2 events per 1000 patient-years) of developing the primary composite renal outcome (doubling of serum creatinine, ESKD, or death from a renal or cardiovascular cause) compared with those randomized to placebo. 68 Prior trials have also suggested cardiovascular benefit with this class of medications, which may extend to patients with CKD who have lower levels of albuminuria. 69 , 70

Nephrotoxins

All patients with CKD should be counseled to avoid nephrotoxins. Although a complete list is beyond the scope of this review, a few warrant mentioning. Routine administration of NSAIDs in CKD is not recommended, especially among individuals who are taking ACE-I or ARB therapy. 5 , 18 Herbal remedies are not regulated by the US Food and Drug Administration, and some (such as those containing aristolochic acid or anthraquinones) have been reported to cause a myriad of kidney abnormalities, including acute tubular necrosis, acute or chronic interstitial nephritis, nephrolithiasis, rhabdomyolysis, hypokalemia, and Fanconi syndrome. 22 Phosphate-based bowel preparations (both oral and enema formulations) are readily available over the counter and can lead to acute phosphate nephropathy. 23 , 24 Proton pump inhibitors are widely used and have been associated with acute interstitial nephritis in case reports and incident CKD in population-based studies. 71 – 73 In the population-based Atherosclerosis Risk in Communities cohort, the incidence of CKD was 14.2 events in those taking proton pump inhibitors and 10.7 per 1000 events in people who did not take them. 71 Uniform discontinuation of proton pump inhibitors in CKD is not necessary. However, indications for use should be addressed at each primary care visit.

Drug Dosing

Adjustments in drug dosing are frequently required in patients with CKD. Of note, the traditional Cockcroft-Gault equation often poorly reflects measured GFR, whereas estimation of GFR using the CKD-EPI equation likely correlates better with drug clearance by the kidneys. 74 , 75 Common medications that require dose reductions include most antibiotics, direct oral anticoagulants, gabapentin and pregabalin, oral hypoglycemic agents, insulin, chemotherapeutic agents, and opiates, among others. 5 , 18 In general, use of medications with low likelihood of benefit should be minimized because patients with CKD are at high risk of adverse drug events. 76 – 79 Gadolinium-based contrast agents are contraindicated in individuals with acute kidney injury, eGFR less than 30 mL/min/1.73 m 2 , or ESKD given the risk of nephrogenic systemic fibrosis, a painful and debilitating disorder characterized by marked fibrosis of the skin and occasionally other organs. 5 , 18 , 80 , 81 Newer macrocyclic chelate formulations (eg, gadoteridol, gadobutrol, or gadoterate) are much less likely to cause nephrogenic systemic fibrosis, but the best prevention may still be to avoid gadolinium altogether. If administration of gadolinium is deemed essential, the patient must be counseled on the potential risk of nephrogenic systemic fibrosis and a nephrologist may be consulted for consideration of postexposure hemodialysis. 5 , 18 , 80 – 82

Dietary Management

Dietary management to prevent CKD progression is controversial since large trials have had equivocal results. 83 – 85 For example, the MDRD study evaluated 2 levels of protein restriction in 840 patients, finding that a low-protein diet compared with usual protein intake resulted in slower GFR decline only after the initial 4 months, and that a very low-protein diet compared with a low-protein diet was not significantly associated with slower GFR decline. Both levels of protein restriction appeared to have benefit in the subgroup with proteinuria greater than 3 g per day, although this group was small. 83 Other, smaller trials have suggested a benefit of protein restriction in the prevention of CKD progression or ESKD. 86 – 88 The KDIGO guidelines recommend that protein intake be reduced to less than 0.8 g/kg per day (with proper education) in adults with CKD stages G4-G5 and to less than 1.3 g/kg per day in other adult patients with CKD at risk of progression. 5 The possible benefits of dietary protein restriction must be balanced with the concern of precipitating malnutrition and/or protein wasting syndrome. 5 , 83 , 84 , 89 Lower dietary acid loads (eg, more fruits and vegetables and less meats, eggs, and cheeses) may also help protect against kidney injury. 90 , 91 Low-sodium diets (generally <2 g per day) are recommended for patients with hypertension, proteinuria, or fluid overload. 5

Monitoring of Established CKD and Treatment of Complications

Once CKD is established, the KDIGO guidelines recommend monitoring eGFR and albuminuria at least once annually. For patients at high risk, these measures should be monitored at least twice per year; patients at very high risk should be monitored at least 3 times per year ( Figure 2 ). 5 Patients with moderate to severe CKD are at increased risk of developing electrolyte abnormalities, mineral and bone disorders, and anemia. 92 Screening and frequency of assessment for laboratory abnormalities is dictated by stage of CKD and includes measurement of complete blood count, basic metabolic panel, serum albumin, phosphate, parathyroid hormone, 25-hydroxyvitamin D, and lipid panel ( Table ). 5 , 50 , 93 , 94

Screening, Monitoring, and Management of the Complications of Chronic Kidney Disease (CKD)

Anemia and the Role of Erythropoietin in CKD

Anemia is among the most common complications of CKD. In a study that included 19 CKD cohorts from across the world, 41% of the 209 311 individuals had low levels of hemoglobin (defined as <13 g/dL in men and <12 g/dL in women). 92 The initial workup of anemia should include assessment of iron stores: those who are iron deficient may benefit from oral or intravenous iron repletion. Patients with hemoglobin levels persistently below 10 g/dL despite addressing reversible causes can be referred to a nephrologist for consideration of additional medical therapy, including erythropoietin-stimulating agents; however, erythropoietin-stimulating agents have been associated with increased risk of death, stroke, and venous thromboembolism, and these risks must be weighed against any potential benefits. 93

Electrolyte, Mineral, and Bone Abnormalities in CKD

Electrolyte abnormalities are present in 3% to 11% of patients with CKD. 92 Initial treatment strategies usually involve dietary restrictions and prescription of supplements. For example, primary care clinicians should recommend low-potassium diets for patients with hyperkalemia and low-phosphorus diets for patients with hyperphosphatemia. 5 , 18 , 94 , 95 For patients with a serum bicarbonate level persistently below 22 mmol/L, oral bicarbonate supplementation should be considered, as studies have suggested that chronic metabolic acidosis is associated with faster CKD progression. 5 , 18 , 96 – 99

Mineral and bone disorders are also common. In a study that included 42 985 patients with CKD, 58% had intact parathyroid hormone levels greater than 65 pg/mL. 92 Although the optimal intact parathyroid hormone level for CKD remains unclear, most nephrologists agree that concomitant hyperphosphatemia, hypocalcemia, and vitamin D deficiency should be addressed, such as with a low-phosphate diet, phosphate binders, adequate elemental calcium intake, and vitamin D supplementation ( Table ). 94 , 95

Prognosis of CKD

The incidence of ESKD varies by the presence of risk factors and geographical location. For example, in North America, the incidence among individuals with eGFR less than 60 mL/min/1.73 m 2 ranged from 4.9 to 168.3 ESKD events per 1000 patient-years in 16 cohorts; in 15 non–North American cohorts, the incidence ranged from 1.2 to 131.3 ESKD events per 1000 patient-years. 100 Most patients with CKD do not require kidney replacement therapy during their lifetime. 101 Simple online tools are available to help with risk stratification. For example, the Kidney Failure Risk Equation (KFRE; https://kidneyfailurerisk.com/ ) predicts the 2-year and 5-year probabilities of requiring dialysis or transplant among individuals with eGFR less than 60 mL/min/1.73 m 2 . 100 , 102 The KFRE, which has been validated in more than 700 000 individuals from more than 30 countries, uses readily available clinical and laboratory variables. The 4-variable equation includes age, sex, eGFR, and urine ACR, whereas the 8-variable equation further incorporates serum albumin, phosphate, calcium, and bicarbonate levels. 100 , 102 Some health systems have tested the implementation of KFRE in clinical practice: nephrology referrals based on a 5-year KFRE greater than 3% led to shorter wait times, 103 and a 2-year KFRE greater than 10% was used to guide referrals to multidisciplinary CKD clinics. 104 An ongoing trial is evaluating whether a KFRE risk-based approach improves CKD management. 105 For patients with eGFR less than 30mL/min/1.73m 2 , the CKD G4+ risk calculator ( https://www.kdigo.org/equation/ ) may provide additional information on the risks of cardiovascular disease and death. 106 , 107 Importantly, risk prognostication may be helpful in not only identifying individuals at high risk of disease progression but also providing reassurance to those with mild CKD such as stage G3a A1.

Referral to a Nephrologist and Timing of Kidney Replacement Therapy

The KDIGO guidelines recommend that patients with CKD be referred to a nephrologist when eGFR falls below 30 mL/min/1.73 m 2 (stage G4) and/or urine ACR increases above 300 mg per 24 hours (stage A3). 5 The presence of albuminuria greater than 2200 mg per 24 hours should prompt expedited evaluation by a nephrologist and consideration of nephrotic syndrome. Additional indications for referral include the following: presence of greater than 20 red blood cells per high-power field of unclear etiology, red blood cell casts on urine microscopy or other indication of glomerulonephritis, CKD with uncontrolled hypertension despite 4 or more antihypertensive medications, persistent hypokalemia or hyperkalemia, anemia requiring erythropoietin replacement, recurrent or extensive kidney stones, hereditary kidney disease, acute kidney injury, and rapid CKD progression (a decrease in eGFR ≥25% from baseline or a sustained decline in eGFR >5 mL/min/1.73 m 2 ). 5 In persons without CKD, even small changes in serum creatinine (eg, from 0.7 mg/dL to 1.2 mg/dL) reflect large declines in eGFR, and primary care clinicians should attempt to identify reversible causes. Indications for kidney biopsy may include but are not limited to unexplained persistent or increasing albuminuria, presence of cellular casts or dysmorphic red blood cells on urine sediment, and unexplained or rapid decline in GFR. 5 Specific thresholds vary depending on patient characteristics and by institution. Patients with polycystic kidney disease, certain types of glomerulonephritis, and nephrotic-range albuminuria are at particularly high risk of progressing to ESKD. 5 , 39 , 102

Referral to nephrology is important for planning kidney replacement therapy and transplant evaluation. The decision to begin kidney replacement therapy is based on the presence of symptoms and not solely on level of GFR. 108 Urgent indications include encephalopathy, pericarditis, and pleuritis due to severe uremia. 109 Otherwise, initiation of dialysis should be individualized and considered when patients have uremic signs or symptoms (eg, nausea, vomiting, poor appetite, metallic taste, pericardial rub or effusion, asterixis, or altered mental status), electrolyte abnormalities (eg, hyperkalemia or metabolic acidosis), or volume overload (eg, pulmonary or lower extremity edema) refractory to medical management. 5 , 18 , 109 A shared decision-making approach is best. Patients should be educated about treatment options and actively contribute to decision-making. Early education should include information on the potential complications of CKD as well as the different modalities of kidney replacement therapy. Kidney transplantation is considered the optimal therapy for ESKD, with living donor kidney transplantations performed before or shortly after dialysis initiation having the best outcomes. 110 , 111 As such, early referral (eg, eGFR <30 mL/min/1.73 m 2 and an elevated 2-year risk of ESKD) for transplant evaluation is important. 112 , 113 Alternative therapies for ESKD may include in-center hemodialysis, home hemodialysis, peritoneal dialysis, or conservative care without dialysis. 107 Patient preference should be taken into consideration when selecting dialysis modality; however, patients with multiple abdominal surgeries with resultant peritoneal scarring or unstable housing are likely poor candidates for peritoneal dialysis. 107 , 109 Patients planning for hemodialysis who exhibit rapid decline in eGFR should be referred to an experienced vascular surgeon for arteriovenous fistula placement. The KDOQI guidelines recommend that access creation should occur when eGFR is between 15 and 20 mL/min/1.73 m 2 . 114 Of note, dialysis initiation has been associated with accelerated functional decline and high short-term mortality among older patients with poor functional status. 115 , 116 Patient preferences for conservative approaches to medical management should be discussed and honored.

Conclusions

Chronic kidney disease affects 8% to 16% of the population worldwide and is a leading cause of death. Optimal management of CKD includes cardiovascular risk reduction, treatment of albuminuria, avoidance of potential nephrotoxins, and adjustments to drug dosing. Patients also require monitoring for complications of CKD, such as hyperkalemia, metabolic acidosis, anemia, and other metabolic abnormalities. Diagnosis, staging, and appropriate referral of CKD by primary care clinicians are important in reducing the burden of CKD worldwide.

Funding/Support:

Dr Chen was supported by a Clinician Scientist Career Development Award from Johns Hopkins University and is supported by a George M. O’Brien Center for Kidney Research Pilot and Feasibility Grant from Yale University and award K08DK117068 from the National Institutes of Health/NIDDK. Dr Grams is supported by NIDDK grants DK1008803, DK100446, and DK115534.

Role of the Funder/Sponsor: The supporting institutions had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

Conflict of Interest Disclosures: Dr Chen reported receipt of grants from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and Yale University. Dr Grams reported receipt of grants from the NIDDK and the National Kidney Foundation and travel support from Dialysis Clinics Inc for an invited speakership at a directors’ meeting in May 2019. No other disclosures were reported.

Submissions: We encourage authors to submit papers for consideration as a Review. Please contact Edward Livingston, MD, at Edward. gro.krowtenamaj@notsgnivil or Mary McGrae McDermott, MD, at ude.nretsewhtron@806mdm .