In-Depth Topic Review

Am J Nephrol 2021;52:98–107 Received: December 6, 2020

Accepted: January 17, 2021
DOI: 10.1159/000514550 Published online: March 22, 2021

Global Epidemiology of End-Stage

Kidney Disease and Disparities in Kidney
Replacement Therapy
John S. Thurlow a, b Megha Joshi a, b Guofen Yan c Keith C. Norris d
       

Lawrence Y. Agodoa e Christina M. Yuan a, b Robert Nee a, b

     

aNephrology Service, Walter Reed National Military Medical Center, Bethesda, MD, USA; bDepartment of Medicine,
Uniformed Services University, Bethesda, MD, USA; cDepartment of Public Health Sciences, University of Virginia
School of Medicine, Charlottesville, VA, USA; dDepartment of Medicine, David Geffen School of Medicine, University
of California at Los Angeles, Los Angeles, CA, USA; eOffice of the Director, National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA

Keywords survival, population demographic shifts, higher prevalence

Global epidemiology · End-stage kidney disease · Kidney of ESKD risk factors, and increasing KRT access in countries
replacement therapy · Dialysis · Hemodialysis · Peritoneal with growing economies. Unadjusted 5-year survival of
dialysis · Kidney transplant · Disparities · Income · Mortality ESKD patients on KRT was 41% in the USA, 48% in Europe,
and 60% in Japan. Dialysis is the predominant KRT in most
countries, with hemodialysis being the most common mo-
Abstract dality. Variations in dialysis practice patterns account for
Background: The global epidemiology of end-stage kidney some of the differences in survival outcomes globally. World-
disease (ESKD) reflects each nation’s unique genetic, envi- wide, there is a greater prevalence of KRT at higher income
ronmental, lifestyle, and sociodemographic characteristics. levels, and the number of people who die prematurely be-
The response to ESKD, particularly regarding kidney replace- cause of lack of KRT access is estimated at up to 3 times high-
ment therapy (KRT), depends on local disease burden, cul- er than the number who receive treatment. Key Messages:
ture, and socioeconomics. Here, we explore geographic vari- Many people worldwide in need of KRT as a life-sustaining
ation and global trends in ESKD incidence and prevalence treatment do not receive it, mostly in LMICs where health
and examine variations in KRT modality, practice patterns, care resources are severely limited. This large treatment gap
and mortality. We conclude with a discussion on disparities demands a focus on population-based prevention strategies
in access to KRT and strategies to reduce ESKD global burden and development of affordable and cost-effective KRT.
and to improve access to treatment in low- and middle-in- Achieving global equity in KRT access will require concerted
come countries (LMICs). Summary: From 2003 to 2016, inci- efforts in advocating effective public policy, health care de-
dence rates of treated ESKD were relatively stable in many
higher income countries but rose substantially predomi- This is a work of the US Government and is not subject to copyright
nantly in East and Southeast Asia. The prevalence of treated protection in the USA. Foreign copyrights may apply.
ESKD has increased worldwide, likely due to improving ESKD Published by S. Karger AG, Basel.

karger@[Link] © 2021 S. Karger AG, Basel Robert Nee

[Link]/ajn Nephrology Service, Walter Reed National Military Medical Center
8901 Wisconsin Avenue
Bethesda, MD 20889 (USA)
[Link] @ [Link]
livery, workforce capacity, education, research, and support at the country level, and when data are available dispari-
from the government, private sector, nongovernmental, and ties at the individual level within a country. We conclude
professional organizations. © 2021 S. Karger AG, Basel with a discussion of strategies to reduce global ESKD bur-
den and inequities in KRT access.

Introduction Geographic Variation and Global Trends in the

Incidence of Treated ESKD
End-stage kidney disease (ESKD) is a rapidly increas-
ing global health and health care burden. The inability to Based on the International Society of Nephrology’s
care for many patients at risk for and in need of treatment (ISN) 2019 Global Kidney Health Atlas (GKHA) cross-sec-
for ESKD disproportionately impacts low- and middle- tional survey of 160 participating countries, information on
income countries (LMICs). Defining global ESKD epide- treated ESKD incidence was available in 79 countries, and
miology is an essential first step in evaluating interna- the average number of new ESKD diagnoses worldwide was
tional response. In this review, we explore geographic 144 individuals per million general population (pmp) [3].
variation and global trends in treated ESKD incidence In 2016, USRDS-reported incidence rates of treated ESKD
and prevalence based on national reports and registry varied greatly across countries (see online suppl. Table 1;
data. The United States Renal Data System (USRDS) see [Link]/doi/10.1159/000514550 for all online
compiles and publishes international survey data annu- suppl. material) [1]. Taiwan, the USA, the Jalisco region of
ally from 79 countries and regions [1]. Data include only Mexico, and Thailand reported the highest incidences of
those ESKD patients who are on dialysis or have received treated ESKD (493, 378, 355, and 346 pmp/year, respec-
a kidney transplant (i.e., treated ESKD). This underesti- tively). The lowest treated ESKD incidences, ranging from
mates true incidence and prevalence, due to unrecog- 22 to 85 pmp/year, were reported by South Africa, Ukraine,
nized ESKD and limited access to kidney replacement Belarus, Bangladesh, Russia, Jordan, Peru, Colombia, Iran,
therapy (KRT) in many countries. Notably, national Albania, and Estonia.
ESKD data are not available in many LMICs in Africa and Among high-income countries (HICs), ESKD inci-
2 populous developing nations – China and India. dence is the lowest in Nordic countries, other European
The international response to ESKD is complex, influ- countries, Australia, and New Zealand [4]. These have
enced by local disease burden, culture, and socioeconom- nearly universal health care systems, including KRT ac-
ics. An estimated 2.6 million people received KRT world- cess, so the lower rates could be due to relatively low in-
wide in 2010 [2]. However, 4.9–9.7 million people were cidence or delayed chronic kidney disease (CKD) pro-
estimated to require KRT in 2010, suggesting that ≥2.3 gression. Other potential explanations include dialysis
million people might have died because of lack of access commencement at lower glomerular filtration rates,
to this life-sustaining therapy. Thus, only half or less of all greater adoption of conservative care management, and
people needing KRT worldwide had access to it. Further, health care reform strategies focusing on cost contain-
the proportion of people with ESKD not receiving KRT ment [5]. ESKD incidence is much higher in the USA and
was much higher in low (96%) and lower-middle (90%) high-income East and Southeast Asian countries, likely
income countries than in upper-middle (70%) and high reflecting greater CKD burden and associated risk factors
(40%) income countries [3]. The largest treatment gaps such as diabetes, hypertension, obesity, and glomerular
occurred in low-income countries, particularly in Asia diseases (e.g., IgA nephropathy in Asia), greater health
and Africa. In Asia, 17–34% of people needing KRT re- care spending, and improving survival among those with
ceived treatment. In Africa, 9–16% of people needing CKD. Government policies have also improved KRT ac-
KRT received treatment [2]. By 2030, worldwide use of cess. In Taiwan, the National Health Insurance program
KRT is projected to more than double to 5.4 million peo- provides full coverage for dialysis therapy without copay-
ple, with the most growth in Asia [2]. ment [6]. In Thailand, implementation of a “PD-first”
Given the anticipated global growth in ESKD, it is im- universal coverage policy in which all eligible patients are
perative to understand how international outcomes differ offered peritoneal dialysis (PD) with the more costly he-
according to KRT management strategies. Therefore, we modialysis (HD) restricted to patients with a clinical in-
examine international variations in KRT modality and dication or private insurance coverage has led to expan-
practice patterns, mortality, disparities in access to KRT sion of ESKD care [7].

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DOI: 10.1159/000514550
 Among HICs, the incidence rate trends for treated mainly due to unjust social and economic policies [12].
ESKD are relatively stable, either declining modestly or Social determinants of health include health services (e.g.,
increasing slightly by ∼2 pmp/year from 2003 to 2016, access to and quality of care and insurance status), social
including Nordic and other European countries, Austra- environment (e.g., discrimination, income, and educa-
lia, New Zealand, Japan, and the USA [1]. This may sug- tion level), physical environment (e.g., place of residence,
gest that treatment of diabetes and hypertension has im- living conditions, and transportation), health literacy,
proved over this 14-year period, reducing CKD onset and and legislative policies [13, 14]. The maldistribution of
slowing its progression [4]. In contrast, treated ESKD in- these factors is associated with increased development
cidence rates have risen substantially from 2003 to 2016 and progression of CKD and CKD risk factors, lower ac-
in East and Southeast Asian countries, including Thai- cess to health care, and worse morbidity and mortality in
land, Malaysia, the Republic of Korea, Singapore, the the CKD and ESKD population [15].
Philippines, and Taiwan [1]. This may reflect an aging
population; an increased burden of diabetes, hyperten-
sion, and obesity; and economic development that im- Geographic Variation and Global Trends in the
proved KRT access [8]. Prevalence of Treated ESKD

In 2016, 2,455,004 patients were treated for ESKD

Incidence Rates of ESKD in the USA across all countries reporting data to the USRDS [1]. Based
on the ISN’s 2019 GKHA survey, information on treated
Since 2011, the crude ESKD incidence rate in the USA ESKD prevalence was available in 91 countries, and the
has risen; however, the age-sex-race standardized incidence average number of people receiving treatment for ESKD
rate appears to have plateaued [1]. The standardized ESKD globally was 759 pmp [3]. The USA has the most, with
incidence rate rose sharply in the 1980s and 1990s, leveled 709,501 treated patients (29%), followed by Japan (328,000;
off in early 2006, and has declined slightly since. This down- 13%) and Brazil (180,000; 7%). Treated ESKD prevalence
ward trend may suggest improved prevention or delay of varied nearly 30-fold across represented countries (online
ESKD onset. However, projected demographic, clinical, suppl. Table 1) [1, 16]. Taiwan reported the highest treat-
and lifestyle characteristics of the US population may re- ed ESKD prevalence (3,392 pmp), followed by Japan
verse the current downward trend. A simulation model in- (2,599 pmp) and the USA (2,196 pmp). The lowest preva-
corporating trends in population demographics, obesity, lences, 117–540 pmp, were reported by Bangladesh, South
diabetes, and hypertension projected an 11–18% increase in Africa, Ukraine, Belarus, Iraq, Russia, Indonesia, Guate-
crude incidence rate from 2015 to 2030 [9]. Combined with mala, Albania, Peru, Latvia, Serbia, and Bulgaria.
ESKD mortality declines, this could increase prevalence by Although ESKD incidence has stabilized or decreased
29–68%. The projected rise in ESKD incidence and preva- in many countries, ESKD prevalence has increased by a
lence in the USA is due to an aging population, rising dia- median 43% from 2003 to 2016 [1]. Countries with the
betes and hypertension burden, decreasing ESKD mortality highest percentage rise in ESKD prevalence were Taiwan,
due to improved care, and an increasing proportion of Af- the USA, the Republic of Korea, Thailand, the Jalisco re-
rican-Americans in the US population. gion of Mexico, Chile, Malaysia, Turkey, Brazil, the Phil-
African-Americans and other racial/ethnic minority ippines, and Russia [1]. Rising ESKD prevalence world-
and socially disadvantaged groups account for a dispro- wide may be due to improved survival; aging of the world
portionate share of the ESKD population in the USA, population; increases in diabetes, hypertension, and obe-
largely reflecting inequities in health care access and de- sity, associated with urbanization and changes in diet and
livery and associated increased disease burden and poor physical activity; and increasing KRT access in countries
clinical outcomes [10]. Mechanisms underlying these ra- with growing economies [2, 4].
cial and ethnic disparities represent a complex interplay
of genetic, biological, environmental, sociocultural, so-
cioeconomic, and health care system level factors [11]. ESKD in China, India, and Africa
According to the World Health Organization Commis-
sion on Social Determinants of Health, the social gradient In China, the most populous country in the world (1.4
in health within and between countries is caused by un- billion people), there are ongoing efforts to establish a
equal distribution of power, income, goods, and services, national kidney registry [17]. The China Kidney Disease

100 Am J Nephrol 2021;52:98–107 Thurlow/Joshi/Yan/Norris/Agodoa/

DOI: 10.1159/000514550 Yuan/Nee
Network (CK-NET) was initiated in 2014, with its mis- because of the relatively low number of incident cases. In
sion to integrate various sources of data in China to better some countries, by focusing on transplantation or home
inform health care policy, strengthen academic research, dialysis, <1/3 of ESKD patients used in-center HD [4].
and promote effective management in patients with kid- These include Hong Kong, Estonia, the Netherlands,
ney disease. Using 2 large nationwide claims databases New Zealand, and some Nordic countries. This differs
(China Health Insurance Research and Commercial from many East and Southeast Asian countries where
Health Insurance), the estimated age-adjusted incidence ≥85% of patients receive in-center HD. Japan is notable
rate of dialysis was 122 pmp/year. Also, in 2015, the esti- because it has a large and mature ESKD program with
mated prevalence of HD and PD was 402 and 40 pmp, excellent clinical outcomes, but very low transplantation
respectively (553,000 HD and 55,000 PD patients). and home dialysis use. In-center HD is favored over home
India, the 2nd most populous country in the world, dialysis partly for historical reasons (dialysis facilities are
also lacks a national registry for ESKD [18]. Most esti- available and easily accessible, with many placed inten-
mates are extrapolated from subregions of India or hos- tionally near public transportation stops), and kidney do-
pital-based registries. A population-based study from a nation rates are low, in part due to spiritual beliefs.
large urban cohort estimated an age-adjusted ESKD inci- Worldwide, HD is the most common dialysis modality
dence of 232 pmp [19]. In 2010, 52,273 adult CKD pa- [26]. In 2016, in most countries, ≥80% of chronic dialysis
tients were analyzed, and 61% of those with ESKD were patients received in-center HD [1]. Home HD therapy was
not on any form of KRT, 32% were on HD, 5% on PD, provided to 9 and 17% of dialysis patients in Australia and
and 2% were evaluated for transplant [20]. New Zealand, respectively [1]. PD was used by 71% of di-
In Africa, the vast majority of cases of ESKD likely re- alysis patients in Hong Kong, by 61% in the Jalisco region
main undiagnosed and untreated, leading to almost cer- of Mexico, and by 57% in Guatemala [1]. While interna-
tain mortality [21]. Limited aggregate data exist to accu- tional differences in dialysis outcomes derive to some ex-
rately characterize ESKD rates, which are likely quite tent from variations in patient population, survival differ-
high, and steps to establish a continent-wide registry are ences may also be affected by modifiable variation in dialy-
ongoing [22]. The prevalence of treated ESKD in sub-Sa- sis practices, including vascular access, HD session duration,
haran Africa is lower than that of other developing coun- and dialysis adequacy [4], based on global data reported by
tries (<100 pmp) [23, 24], despite comparable incidence the USRDS and observational data from the international
rates, and is likely due to limited access to KRT (only prospective cohort study of HD patients in Dialysis Out-
∼10% of adults with incident ESKD remained on dialysis comes and Practice Patterns Study (DOPPS) [27].
≥3 months) [21]. KRT access generally requires self-
funding, even in wealthier countries like South Africa,
which only provides government funding for KRT if a Vascular Access
patient is eligible for transplant [25].
The native arteriovenous fistula (AVF) is widely con-
sidered the preferred option of vascular access for most
Global Variation in KRT Modality and Practice HD patients, providing the best outcomes overall com-
Patterns pared with arteriovenous grafts (AVG) or central venous
catheters (CVC) [28]. In 2013, Japan and Russia had the
Although kidney transplantation is the preferred treat- highest prevalent use of AVF (>90%) among 20 partici-
ment for eligible ESKD patients, dialysis is the predomi- pating countries in the DOPPS [29]. AVF use in prevalent
nant therapy in the majority of countries (online suppl. HD patients was 49–92% across these DOPPS countries,
Table 2) [1]. Considerable variation exists in access to and while catheter use ranged from 1 to 45% [29]. In the USA,
use of kidney transplantation. In 2013, transplantation the Centers for Medicare & Medicaid Services’ (CMS)
for ESKD patients ranged from 57–72% in Nordic coun- Fistula First Breakthrough Initiative spurred increased
tries, Estonia, and the Netherlands to <10% in some Asian AVF use (24 to 68%) and decreased AVG (49 to 18%) and
and eastern European countries [4]. Countries with the CVC use (27 to 15%) from 1997 to 2013 [29]. Large vari-
highest transplantation rates – mostly Nordic and several ations in vascular access type also exist in other regions of
other European countries – also have some of the lowest the world. In South Africa, the prevalence of AVF, AVG,
ESKD incidence rates. In such countries, transplantation and CVC was 51, 7, and 39%, respectively, in 2017 [30].
may be offered to a higher proportion of ESKD patients In Argentina, the prevalence of AVF, AVG, and CVC was

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DOI: 10.1159/000514550
70, 15, and 15%, respectively, in 2018 [31]. In Vietnam, pool Kt/V (spKt/V) of 1.4 per HD session for patients
the prevalence of AVF, AVG, and CVC was >95, 4, and treated thrice weekly, with a minimum delivered spKt/V
1%, respectively, in 2018 [32]. Further, DOPPS data dem- of 1.2 [42]. Since 1996, an increase in dialysis dose has
onstrate substantial international differences in the cre- been observed with lower proportions of HD patients
ation location and successful use of AVFs [33]. Specifi- with spKt/V <1.2 in DOPPS countries [43]. Recent
cally, successful use of newly created AVFs (≥30 days of DOPPS data from 2015 to 2018 showed that 34% of HD
continuous use) was 87% in Japan, 67% in Europe/Aus- patients from GCC countries had low spKt/V <1.2 versus
tralia and New Zealand, and 64% in the USA. Median 5–17% in Canada, Europe, Japan, and the USA [41]. In
time until first successful AVF use was 10 days in Japan, the USA, Kt/V dose (not dialysis duration) is tied to the
46 days in Europe/Australia and New Zealand, and 82 CMS’ payment policy to dialysis facilities, with 97% of
days in the USA. The factors that may explain these AVF HD patients achieving spKt/V ≥1.2 [1]. In Japan, treat-
outcomes include differences in patient characteristics, ments are longer, with lower blood flow rates, thought to
surgical training, dialysis unit staffing, and HD prescrip- better ensure hemodynamic stability and greater middle
tion such as dialysis blood flow [34]. molecule clearance, despite a greater likelihood of spKt/V
<1.2 [4]. Among 5,784 HD patients from Japan DOPPS
from 1999 to 2011, spKt/V <1.2 was observed in 26% of
Hemodialysis Session Duration patients and was associated with greater mortality (ad-
justed hazard ratio per 0.1 lower spKt/V = 1.10; 95% CI:
Although a recent pragmatic trial evaluating the effect 1.05–1.14) [44]. However, survival in the Japanese HD
of session duration on clinical outcomes was inconclusive population overall is considerably better than most other
[35], multiple observational studies have demonstrated an countries, with a crude mortality of 9.8% in 2013 [45].
association between longer treatment time and improved Thus, despite this relatively low mortality rate, opportu-
survival among HD patients [36–38]. In many HICs, in- nities remain to improve the dialysis dose in Japan. In
center HD treatment time is ≥4 h thrice weekly, with Aus- LMICs such as India, twice-weekly HD is a common
tralia/New Zealand, Germany, and Sweden having some practice, with about one-fourth of patients undergoing
of the longest treatment times among DOPPS countries dialysis once a week or “as needed” due to financial con-
[37]. More recent data indicated that 92% of patients dia- straints [46]. In a single-center study of 463 HD patients
lyzed in Australia had session lengths from 240 to 300 min in Southern India, only 50% of the treatments delivered a
[39]. In contrast, dialysis session length has shortened in spKt/V ≥1.0 [47]. In another single-center study of 50 pa-
the USA (mean 214 min) [37] with higher dialysis blood tients on twice-weekly HD, only 28% of sessions delivered
flow and larger dialyzer size versus other DOPPS coun- standardized Kt/V ≥2.0 per week (mean 1.4) [48].
tries, partly because of greater reliance on small solute
(urea) clearances as a measure of dialysis adequacy than
other metrics such as volume management and patient- Global Variation in Mortality Rates in ESKD
reported outcomes [40]. This variation in session length
reflects an interplay between clinical practice guidelines, According to the 2013 Global Burden of Disease Study,
reimbursement measures, HD unit policies, and provider age-standardized death rate caused by CKD increased
and patient preferences [4]. Dialysis treatment time is from 11.6 to 15.8 per 100,000 between 1990 and 2013
similarly short in the Gulf Cooperation Council (GCC) [49]. In 2013, CKD ranked 19th for global years of life
countries (Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, lost, a measure of premature death. Although most ESKD
and the United Arab Emirates) based on DOPPS data registries report incidence and prevalence data, survival
from 2012 to 2018, with a mean of 222 min and 43% prev- data are preponderantly from HICs (online suppl. Table
alence for low treatment time (<240 min) [41]. 1). For patients with ESKD onset from 2004 to 2008,
treated with dialysis or transplantation, unadjusted 5-year
survival was 41% in the USA, 48% in Europe, and 60% in
Dialysis Adequacy Japan, despite patients being 2–3 years older on average
in Europe and Japan versus the USA and Japan having
The 2015 update of the Kidney Disease Outcomes few transplant patients [4]. Excluding transplant, unad-
Quality Initiative (KDOQI) Clinical Practice Guideline justed 5-year survival for dialysis was 39% in the USA,
for Hemodialysis Adequacy recommends a target single 41% in Europe, and 60% in Japan [4]. The European Re-

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nal Association-European Dialysis and Transplant Asso- low-income countries [3]. Although patients receiving
ciation (ERA-EDTA) Registry Annual Report 2016 KRT represent a small fraction of the global population
showed that for patients starting dialysis from 2007 to (∼0.038%) [2], they absorb 2–4% of the health care bud-
2011 across European countries, 5-year unadjusted sur- get of some countries, creating problems of prioritization
vival was stable at 42% [50]. DOPPS analyses demon- and opportunity costs [57]. Dialysis in LMICs is primar-
strate that demographic factors and comorbid diseases ily provided in the private sector, and high out-of-pocket
accounted for some, but not all, of the differences in di- expenses often lead to household financial depletion, fol-
alysis mortality between the USA, Europe, and Japan lowed by treatment discontinuation and death once re-
[51]. Other factors, such as variations in dialysis practice, sources are exhausted [58]. In a single-center study of 320
may contribute to differing survival outcomes. ESKD patients initiated on maintenance HD in Nigeria,
>80% of the patients funded dialysis treatments from out-
of-pocket payment [59]. Within 12 weeks of initiation,
Mortality in the USA 98% had dropped out of the program through deaths and
abandonment, and only 2% were able to fund treatments
In 2016, adjusted mortality rates for ESKD, dialysis, beyond 12 weeks.
and transplant patients were 134, 164 (166 for HD and Disparity in access to KRT is not limited to LMICs.
154 for PD patients), and 29 per 1,000 patient-years, re- Some of the most explicit examples of inequity are evi-
spectively [1]. Overall mortality rates among ESKD (di- dent in undocumented immigrant ESKD care. In the
alysis and transplant) patients have declined from 2001 to USA, undocumented immigrants with ESKD (currently
2016, with rates leveling during recent years (the adjusted estimated between 5,500 and 8,857) [60] are ineligible for
death rate decreased by 29% over this period). Specifi- Medicare, and coverage decisions are made at state or lo-
cally, reductions in adjusted mortality rates from 2001 to cal levels [61]. The 2 main treatment options, emergency-
2016 were 28% for HD and 43% for PD patients. The rea- only hemodialysis (EOHD) and chronic outpatient dialy-
sons for increased ESKD survival are unknown, but may sis, highlight the dilemma between principles of justice
relate to technical advances in dialysis, new pharmaceuti- and societal standards. Some patients on EOHD are dia-
cal agents, and improved practice guidelines adherence lyzed once to twice weekly while others just once a month
[52]. Increased access to transplant and improved al- [62]. Not surprisingly, EOHD is associated with psycho-
lograft survival may also be contributory. Nonetheless, social distress, life-threating physical symptoms, and
absolute mortality rates remain high in ESKD, particu- poor outcomes with a mean dialysis vintage of 16 months
larly for maintenance dialysis. at the time of death [63, 64]. A retrospective cohort study
involving 211 undocumented patients in 3 states demon-
strated a 14-fold increase in 5-year relative hazard of mor-
Global and Socioeconomic Disparities in the Burden tality for EOHD versus standard chronic outpatient di-
of ESKD and Access to KRT alysis [65]. Enrollment in private health insurance cover-
age and subsequent standard thrice weekly dialysis results
CKD is a global health challenge, especially in LMICs in improved 1-year mortality and cost savings in undocu-
[53]. A majority of people in developing countries have mented patient care [66]. In 12 states, undocumented im-
limited incomes and cannot afford health insurance, migrants are able to receive chronic outpatient dialysis
which risks personal financial crises from out-of-pocket through Emergency Medicaid coverage [67]. In other
medical costs for both CKD care and KRT [54]. There is states, outpatient dialysis services may be acquired
a greater prevalence of KRT among groups of people with through private insurance (sometimes provided by non-
a higher income level [55], which is consistent with the profit and charitable organizations) or through county-
notion that KRT access is highly dependent on health care funded and safety-net hospital-funded outpatient dialysis
expenditures and economic strength of individual coun- centers. Thus, ESKD care for this vulnerable population
tries (online suppl. Table 2) [56]. Most KRT patients is highly variable between states, leaving many undocu-
(93%) live in high-income and upper-middle-income mented patients relying on EOHD with resultant poor
countries, with only 7% living in lower-income countries health outcomes that can only be ameliorated by clini-
[2]. The ISN’s 2019 GKHA survey showed a treated ESKD cally sound, humane, and economically sensible health
prevalence of 966 pmp in high-income, 550.2 pmp in up- policy [68].
per-middle, 321 pmp in lower-middle, and 4.4 pmp in

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Table 1. Strategies to reduce global burden of ESKD and inequities in access to KRT

1. Promote a global focus on creating and supporting a culture of health, with an emphasis on primary prevention of CKD
2. Increase awareness of CKD as a public health issue among the population, health care providers, and policymakers
3. Implement effective and affordable early detection, prevention, and treatment programs for CKD
Management of noncommunicable diseases to include hypertension, diabetes, obesity, and cardiovascular disease
Blockade of the renin-angiotensin system
Prevention of AKI and CKD from environmental exposures (nephrotoxic effects from herbal medicines and contaminated water
and soil)
Management of communicable diseases to include HIV and waterborne diseases
4. Develop an appropriate national government policy of KRT delivery to promote equity in resource allocation
5. Promote cost-effective home dialysis modality such as PD and develop affordable dialysis techniques (using domestic
manufacturing of dialysis consumables to reduce costs, point-of-care dialysate production)
6. Lower barriers for patients to receive kidney transplant since it is the most cost-effective KRT modality and results in the best
clinical outcomes (using generic immunosuppressive drugs)
7. Finance prevention and treatment of ESKD with a mix of government, private, and nongovernmental, not-for-profit funding
8. Assess and promote approaches in relation to the local and national levels of economic development and resources through a lens
of justice and equity
9. Increase manpower resources (nephrologists, nephrology nurses, dialysis technicians, and general practitioners)
10. Educate and train local community experts in partnership with governments, nongovernmental organizations, and the
pharmaceutical industry
11. Implement global evidence-based guidelines and professional standards in the provision of KRT with guidance on ethical issues

ESKD, end-stage kidney disease; KRT, kidney replacement therapy; CKD, chronic kidney disease; PD, peritoneal dialysis; AKI, acute
kidney injury; HIV, human immunodeficiency virus.

Significant global inequities also exist for kidney trans- Strategies to reduce ESKD burden and KRT access in-
plantation, which is the most cost-effective treatment for equities at a provider level include early CKD detection,
ESKD (particularly beyond the first year after transplant) prevention and treatment programs with attention to ed-
due to reduced costs and improved survival and quality ucation and lifestyle intervention, communicable diseas-
of life outcomes [69]. Gross domestic product per capita es, noncommunicable diseases (hypertension, diabetes,
correlates with kidney transplant prevalence and kidney obesity, and cardiovascular disease), and avoidance of
transplant as a proportion of overall KRT population, re- nephrotoxic agents (including over-the-counter and
flecting greater transplant rates in HIC [55]. Unmet needs nontraditional remedies) [72]. At a community/system
for kidney transplantation disproportionately affect level, reductions in environmental toxins (air pollutants,
LMICs due to a lack of health care infrastructure, costs of heavy metals, agrichemicals, and contaminated water and
transplant surgery and immunosuppressive drugs, infec- soil) [73], improved access to healthy foods, education,
tious disease (e.g., tuberculosis), geographic remoteness, and healthy living conditions by ensuring equitable ac-
commercial incentives that favor dialysis, lack of a legal cess to housing and employment, health care provider ca-
framework governing brain death, and religious and cul- pacity building, health system organization, and govern-
tural beliefs [70]. In a single-center study of subsidized ment policy grounded in environmental, social, and eco-
kidney transplantation in a public-sector hospital in In- nomic justice are necessary [55, 74, 75]. Table  1 lists
dia, 82% patients experienced financial crisis [71]. Great- strategies to improve KRT access within an ethical frame-
er than 20% of the transplant recipients sold property as work [76], through consideration of affordability, avail-
a source of funding for treatment-related expenditure, ability, and acceptability in KRT delivery [2, 77]. Using
and a majority did not have identified means to pay for these strategies, a country may develop a tailored nation-
immunosuppressive medications [71]. al management program that could account for resource

104 Am J Nephrol 2021;52:98–107 Thurlow/Joshi/Yan/Norris/Agodoa/

DOI: 10.1159/000514550 Yuan/Nee
limitations and local needs [54]. International programs opment of affordable and cost-effective KRT. Achieving
such as Kidney Disease Improving Global Outcomes global equity in access to KRT will require concerted ef-
(KDIGO) provide direction on how to adapt HIC-driven forts in advocating effective public policy, health care de-
guidelines for LMICs [78]. LMICs can leverage support livery, workforce capacity, education, research, and sup-
from international organizations (e.g., ISN), industry, port from the government, private sector, nongovern-
and academic medical centers to address workforce ca- mental, and professional organizations.
pacity through educational ambassador programs, sister
kidney centers, fellowships, web-based teaching pro-
grams, and telemedicine [79]. Finally, health information Acknowledgements
systems, such as registries, are essential in permitting ac-
curate problem assessment and guiding resource alloca- Part of this manuscript was based on the Epidemiology and
Outcome of ESKD topic for the updated American Society of Ne-
tion and policy development [80]. phrology’s online Dialysis Core Curriculum, presented by Dr. Nee
and Dr. Yuan.

Conclusions
Conflict of Interest Statement
In this review, we explore the global epidemiology of
ESKD and inequities in access to KRT. The incidence The authors declare no conflicts of interests.
rates of treated ESKD have remained relatively stable
from 2003 to 2016 in many higher-income countries
(Nordic and other European countries, Australia, New Funding Sources
Zealand, Japan, and the USA) but have risen substantial-
This research did not receive any funding from agencies in the
ly, predominantly, in East and Southeast Asian countries. public, commercial, or not-for-profit sectors. Dr. Yan is supported
The prevalence of treated ESKD has increased worldwide, in part by the National Institutes of Health/National Institute of
likely due to improving ESKD survival, population de- Diabetes and Digestive and Kidney Diseases grant R01DK112008.
mographic shifts, higher prevalence of risk factors for Dr. Norris is supported by NIH grants UL1TR000124 and
ESKD, and increasing KRT access in countries with grow- P30AG021684.
ing economies. Unadjusted 5-year survival of ESKD pa-
tients receiving KRT was 41% in the USA, 48% in Europe,
and 60% in Japan. Dialysis is the predominant KRT in the Author Contributions
majority of countries, with HD being the most common Concept and design: R.N. and C.M.Y.; manuscript drafting:
modality. Variations in dialysis practice patterns account J.T., M.J., G.Y., K.C.N., C.M.Y., and R.N.; manuscript critical revi-
for some of the differences in survival outcomes globally. sions: J.T., K.C.N., L.Y.A., C.M.Y., and R.N. All authors approved
Worldwide, there is a greater KRT prevalence in higher- the final version for submission.
income populations, and the number of people who die
prematurely because of lack of KRT access is estimated at
up to 3 times higher than the number who receive treat- Disclaimer
ment. Greater than 90% of ESKD patients receiving KRT
The views expressed in this review article are those of the au-
in the world live in high-income and upper-middle-in- thors and do not reflect the official policy of the Department of the
come countries. This large treatment gap demands a fo- Army/Navy/Air Force, the Department of Defense, or the US gov-
cus on population-based prevention strategies and devel- ernment.

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DOI: 10.1159/000514550