Obtaining accurate and comparable estimates of CKD burden across world regions is difficult for several reasons. Identification of disease requires testing for kidney disease measures (e.g., serum creatinine or cystatin C for eGFR, urine albumin, and urine total protein), which are not uniformly performed. Differences across populations may reflect differences in laboratory testing practice because CKD in its early stages is typically asymptomatic, with low awareness of disease. ^, For example, if only eGFR is ascertained, prevalence estimates reflect CKD stages G3–G5 and will be considerably lower than if albuminuria is also ascertained, enabling prevalence estimates of CKD stages G1–G5 and A1–A3. Two populations with equal proportions of CKD also may have different prevalence estimates if one performs near-universal laboratory testing and the other screens only high-risk individuals. In addition, because CKD is defined using kidney disease measures, assays must be standardized to derive comparable estimates. Standardization of creatinine assays has been achieved, and substantial progress has been made for cystatin C ; however, standardization of urine albumin assays is still ongoing. Finally, estimating equations for GFR are not consistently applied, and there is known variation in CKD prevalence when, for example, the Modification of Diet in Renal Disease or different Chronic Kidney Disease Epidemiology Collaboration equations are used. ^, Progress in CKD awareness, testing, definitions, and measurement should enable substantial progress in the field in the coming decade.

Estimates of the prevalence of CKD worldwide vary but generally range between 8% and 16% in different populations. The most accurate CKD prevalence estimates come from nationally representative surveys, such as the National Health and Nutritional Examination Survey (NHANES) in the United States. In this sampling design, people are selected from the general population and undergo detailed physical and laboratory examinations. Estimates of disease prevalence are obtained by weighting sample proportions by inverse probability of selection from the general population. In NHANES 2017–2020, the estimate of U.S. prevalence of CKD based on a one-time measurement of eGFR creatinine (Cr) and urine albumin-to-creatinine ratio was 14.0%, representing 8.4% for stages G1 and G2 with albuminuria A2 or A3 and 5.6% for stage G3 or G4. It should be noted that this study did not assess the chronicity of abnormalities of these measures and thus may have overestimated their prevalence. However, other considerations suggested an underestimation of prevalence of CKD. Markers of kidney damage other than albuminuria were not assessed. People with CKD, stage G5—those undergoing KRT and those with an eGFR < 15 mL/min/1.73 m ² —were not included in the NHANES estimates. In addition, NHANES does not include people living in institutionalized settings or who are involved in the military.

Trends in the prevalence of CKD suggest relative stability over time (13.3% in 2005–2008 to 14.1% in 20171–2020), which is encouraging when one considers the significant increases in the prevalence of diabetes mellitus and obesity. ^,

In Europe, no multinational survey data exist, so studies typically combine data to estimate age- and sex-adjusted CKD prevalence. ^, A recent study of 2.4 million patients with CKD obtained from digital health care systems in nine countries (including Canada and Israel) reported a pooled prevalence of 10%, with heterogeneity in albuminuria testing (a key component of CKD identification) ranging from 11% to >90%. In a study combining 19 general population cohorts from 13 European countries, there was large heterogeneity by country, even when stratified by diabetes, hypertension, and obesity status, with lower rates of CKD stages G3–G5 in central Italy (1%) but higher in northeast Germany (5.9%). Similarly, the prevalence of CKD stages G1–G5 ranged from 3.3% in Norway to 17.3% in northeast Germany. Fig. 18.3 indicates the differences by region in the population aged 45 to 74 years and highlights the relatively localized source populations, which may not be representative of all of Europe. Other limitations noted by the authors included the heterogeneity in laboratory methods, with not all creatinine assays being isotope dilution mass spectrometry standardized, and differences in dietary habits, with certain high-protein diets typical of northern Germany known to influence serum creatinine (Cr), resulting in an underestimate of eGFRcr.

Adjusted prevalence of chronic kidney disease (CKD) stages 1–5 in European populations aged 45–74 years, in isotope dilution mass spectrometry (IDMS) studies.

Prevalence was age and sex adjusted to the EU27 population of 2005. The study names in the uncolored regions are studies that used non–IDMS-standardized creatinine or studies that recruited subjects aged 50+ years.

From Brück K, VS, Gambaro G, et al. CKD prevalence varies across the European general population. J Am Soc Nephrol . 2016;27:2135–2147.

Global estimates of CKD are also heterogeneous ( Table 18.2 ; see also Chapter 73 ). ^{, , ,} A systematic analysis of 33 studies from 32 countries (nearly 50% of the world’s population) has found the crude prevalence of CKD stages G1–G5 ranges in men from 4.5% in South Korea to 25.7% in El Salvador, and in women from 4.1% in Saudi Arabia to 16.0% in Singapore. Underlying studies differed in the creatinine measurement method, eGFRcr equation used, and protocol for assessing albuminuria. Noting these caveats, the authors estimated the age-standardized global prevalence of CKD in 2010 as 10.4% in men and 11.8% in women. They also reported substantial differences by gross national product, with high-income countries estimated to have lower CKD prevalence (8.6% and 9.6% in men and women, respectively) than low- and middle-income countries (10.6% and 12.5%). Of note, a more recent study of the prevalence of CKD in Asian countries offered different estimates for 2020, ranging from 7.0% in South Korea to 34.3% in Singapore.

Diabetes and hypertension are considered the major causes of CKD globally. In the U.S. population with diabetes mellitus, an estimated 38% had CKD in 2017–2020; in the population with hypertension, an estimated 21.5% had CKD, and in the population with obesity, an estimated 16.5% had CKD. The prevalence of CKD by specific cause is difficult to estimate, but if the prevalence of diabetes mellitus in the United States is approximately 10% and more than one-third of people with diabetes mellitus have CKD, then the prevalence of diabetic kidney disease in the U.S. population may be close to 3% to 4%. As trends in the prevalence of kidney disease in those with diabetes mellitus have been estimated to be fairly flat, trends in the prevalence of diabetic kidney disease in the general population likely follow the increasing trends in the prevalence of diabetes.

Compared with estimates of CKD prevalence, information on the incidence of CKD is relatively sparse. Calculation of the incidence—the development of new cases of CKD—requires a population-representative sample, longitudinal follow-up, and regular and comparable ascertainment of kidney measures in everyone. The incidence of disease stemming from clinical populations may not be valid because higher-risk individuals are more likely to receive testing. Noting this limitation, equations for the 5-year risk of incident eGFR <60 mL/min/1.73 m ² have been developed. Covariates include age, sex, race/ethnicity, eGFR, history of CVD, ever smoker, hypertension, body mass index, and albuminuria concentration; in persons with diabetes, additional covariates include diabetes medications, hemoglobin A1c, and their interaction. The risk equations had a median C statistic of 0.845 (25%, 75% range, 0.789–0.890) in the cohorts without diabetes and 0.801 (25%, 75% range, 0.750–0.819) in the cohorts with diabetes. On the other hand, the incidence of disease stemming from population-based cohorts may underestimate CKD incidence due to loss of follow-up and relatively infrequent study visits (e.g., visits every 3 or 5 years).

In the United States, a few long-running prospective cohorts have provided estimates of incident CKD, but the frequency of assessment of kidney measures differed. The Atherosclerosis Risk in Communities study, a cohort of middle-aged Black and White individuals aged 45 to 65 years of age, from 4 U.S. communities, estimated an incidence of 10.4 cases of CKD stages G3–G5/1000 years of follow-up, or a 7.3% incidence over 8.8 years when eGFRcr was assessed every 3 years. The Framingham study, a community-based study of predominantly White individuals with a relatively low rate of diabetes (2.7% vs. 11.4% in the Atherosclerosis Risk in Communities study) and a mean age of 43 years, reported 9.4% of 2585 individuals developed CKD stages G3–G5 in a subsequent visit 18.5 years later. In the Cardiovascular Health Study, a community-based longitudinal study of older adults with a mean age of 72 years, 10% developed CKD stages G3–G5 by year 7 when assessed using eGFRcr, and 19% developed CKD stages G3–G5 when assessed using eGFRcys. In each of these studies, the rate of incident CKD was higher with older age. Notably, none assessed the incidence of albuminuria, so they likely underestimated the incidence of CKD.

Racial differences in incident CKD also exist. In the Coronary Artery Risk Development in Young Adults cohort, a study of Black and White individuals aged 18–30 years, the risk of developing CKD stages G3–G5 (in this study, assessed from eGFRcr and requiring an accompanied 25% decline in eGFR) at 10, 15, or 20 years after baseline was 2.6 times higher in Black participants compared with White participants. Similarly, there were large racial disparities in the Multi-Ethnic Study of Arteriosclerosis (mean age, 60 years), in which Black participants had a more than threefold higher risk of developing CKD stages G3 to G5 (in this study, assessed from eGFRcys and required a ≥1 mL/min/1.73 m ² decline in eGFR) compared with White participants in a population with baseline eGFR > 90 mL/min/1.73 m ² (3.4 cases/1000 years vs. 0.9 cases/1000 years). Incidence rates were higher among participants with eGFR between 60 and 90 mL/min/1.73 m ² , and racial differences persisted, albeit slightly attenuated (26.3 cases/1000 years vs. 18.5 cases/1000 years in Black and White participants, respectively). When modeled as incidence over a lifetime using NHANES and registry data, racial disparities again were present, with African Americans projected to develop CKD stages G3–G5 at younger ages and greater disparities in the incidence of more severe disease ( Fig. 18.4 ).

Cumulative incidence from birth by race and sex of chronic kidney disease (CKD) stage 3a (A), 3b (B), 4 (C), and end-stage renal disease ( ESRD; D).

From Grams ME, Chow EK, Segev DL, et al. Lifetime incidence of CKD stages 3–5 in the United States. Am J Kidney Dis . 2013;62:245–252.

In Europe, the incidence of CKD assessed using eGFRcr and urine albumin excretion >30 mg/day has been reported in the PREVEND cohort, a population-based cohort that oversampled for people with urine albumin concentrations ≥10 mg/L on a first-morning void urine sample. Participants were followed over 10 years at 5 separate visits. The incidence of developing CKD stages G1–G5 was 18.6/1000 person-years; the incidence of developing albuminuria was 13.4/1000 person-years, and the incidence of developing decreased GFR was 5.8/1000 person-years. In an administrative cohort, the incidence of serum creatinine ≥1.7 mg/dL (eGFR ranging from 37–57 mL/min/1.73 m ² for men and 28–43 mL/min/1.73 m ² for women) was 1701 cases/million population in Southampton, United Kingdom, with much higher rates of CKD among older compared with younger inhabitants.

CKD has been increasingly recognized as a top public health priority due to its strong association with adverse outcomes. In some areas of the world, CKD is one of the top five causes of death. The Global Burden of disease estimated that 1.2 million people died from CKD in 2017. Lower GFR and higher albuminuria levels result in a significantly diminished life expectancy at all ages ( Fig. 18.5 ). Part of this increase in mortality is exerted through the higher risk of kidney failure, both untreated and treated by dialysis or transplantation. In addition, earlier stages of CKD are associated with increased risk of death, AKI, CKD progression, CVD, heart failure, and even some types of cancer. In an earlier analysis of general population cohorts and in an updated meta-analysis of 27.5 Million individuals from 114 global cohorts the heat map pattern of risk is consistent across 10 common outcomes ( Fig. 18.6 ). For AKI and other adverse outcomes, risk increases with lower GFR and higher albuminuria are generally independent, with each parameter carrying risk, and higher risk with higher stages of disease. ^, Risk relationships have been observed in low-risk and high-risk groups for ESKD and mortality.

Life expectancy of NHANES participants with or without abnormalities in chronic kidney disease (CKD) measures, 1999–2011. GFR <60 mL/min/1.73 m ² or ACR ≥30 mg/g indicate CKD.

ACR, Urine albumin-to-creatinine ratio; GFR, estimated glomerular filtration rate; NHANES, National Health and Nutrition Examination Survey.

Adapted from U.S. Renal Data System. 2016 USRDS annual data report: epidemiology of kidney disease in the United States. < https://www.ajkd.org/article/S0272-6386(16)30703-X/fulltext >; 2016. Accessed 02.09.2024.

Adjusted hazard ratios of 10 outcomes as a function of CKD eGFR (G-) and albuminuria (A-) stages by heat map colors of risk stages (green = low risk, yellow = moderately increased risk, orange = high risk, and red = very high risk).

Outcome abbreviations (number of events): all-cause mortality (ACM, n=2.6 M), Hospitalizations (Hosp, n=8.4 M), myocardial infraction (MI, n=0.451 M), Stroke (n=0.461 M), peripheral arterial disease (PAD, n=0.378 M), cardiovascular mortality (CVM, n=0.776 M), heart failure (HF, n=1.132 M), atrial fibrillation (AF, n=1.069 M), acute kidney injury (AKI, n=1.408), kidney failure replacement therapy (KFRT, n=0.159 M). Numbers reflect the adjusted hazard ratio compared with the reference cell in a separate analysis for each of the ten outcomes. Adjustment variables included: age, sex, smoking status (current, former, never), systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, body mass index, use of antihypertensive medications, and a history of diabetes, coronary heart disease, stroke, heart failure, atrial fibrillation, peripheral artery disease, cancer, and chronic obstructive pulmonary disease when relevant. The percentile shaded the darkest green color corresponds to the proportion of cells in the grid without chronic kidney disease, and the percentile shaded the darkest red color corresponds to the proportion expected to be at the highest risk for adverse outcomes. In this manner, the numbers of green and red cells are consistent across outcomes, but the patterns are allowed to differ. We omitted the eGFRcr category of 105+ mL/min/1.73 m ² from this figure since this category displays an increased risk for some outcomes.

Data from Writing Group for the CKD Prognosis Consortium. Grams ME, Coresh J, Matsushita K, et al. Estimated glomerular filtration rate, albuminuria, and adverse outcomes: An individual-participant data meta-analysis. JAMA. 2023;3;330(13):1266-1277.

There is intense interest in defining earlier outcomes of CKD progression, with the goal of enhancing drug development and clinical prevention. Provided that there are no acute effects on eGFR, decline in eGFR by 30% to 40% is now accepted by the U.S. Food and Drug Administration as a surrogate outcome for CKD progression, previously assessed by doubling of the serum creatinine level (equivalent to a 57% decline in eGFR) or the development of ESKD. Slope of GFR and changes in albuminuria are also associated with ESKD and death, and these endpoints, as well as remission of the nephrotic syndrome, are used as a surrogate endpoint in trials of some glomerular diseases. ^,

Kidney measures are not the only risk factors for adverse outcomes, and there is a growing literature on the use of other factors to explain variations in the risk of progression to ESKD within stages of CKD. For a given level of GFR or albuminuria, older adults are less likely to experience ESKD than their younger counterparts, possibly due to treatment preference (e.g., refusal of dialysis or transplantation as a therapy) or because of the competing event of death (i.e., older adults with a given level of GFR or albuminuria are relatively more likely to die than progress to ESKD). Moreover, the absolute risks of ESKD and death may vary based on indications for selection into a study population; research study populations often report a higher risk of ESKD than death, whereas clinical population information drawn from medical records data often shows a higher risk of death than ESKD. ^, Regional variation in the absolute risk of progression to ESKD has also been reported. In a validation of a kidney failure risk equation calculator in 31 international cohorts, only the region of cohort was observed to improve calibration for a model that included age, sex, eGFR, and albuminuria. Therefore a regional calibration factor was introduced that incorporated a lower baseline risk by 32.9% at 2 years and 16.5% at 5 years for countries outside North America (see kidneyfailurerisk.com ) ( Fig. 18.7 ). Some of this risk differential may be due to the resources allotted to providing treatment rather than underlying characteristics of the countries themselves.

Refit baseline hazard of original kidney failure risk equation (KFRE) at 2 and 5 years stratified by region.

Box plots show the the centered baseline hazard for the original four-variable kidney failure risk equation (age, 70 years; male, 56%; eGFR, 36 mL/min/1.73 m ² ; urine albumin-to-creatinine ratio (ACR), 170 mg/g) in cohorts within and outside North America. The 25 cohorts included were: AASK , African American Study of Kidney Disease and Hypertension; ARIC, Atherosclerosis Risk in Communities; BC CKD, British Columbia Chronic Kidney Disease; CCF, Cleveland Clinic Foundation; CRIB, Chronic Renal Impairment in Birmingham; CRIC, Chronic Renal Insufficiency Cohort; eGFR, estimated glomerular filtration rate; GCKD, German CKD; GLOMMS, Grampian Laboratory Outcomes, Morbidity and Mortality Studies; HUNT, Nord Trøndelag Health Study; ICES-KDT, Institute for Clinical Evaluative Sciences, Provincial Kidney, Dialysis, and Transplantation; MASTERPLAN, Multifactorial Approach and Superior Treatment Efficacy in Renal Patients With the Aid of a Nurse Practitioner; MDRD, Modification of Diet in Renal Disease; MMKD, mild to moderate kidney disease; NZDCS, New Zealand Diabetes Cohort Study; REGARDS, Reasons for Geographic and Racial Differences in Stroke Study; RENAAL, Reduction of Endpoints in Non–insulin Dependent Diabetes Mellitus With the Angiotensin II Antagonist Losartan; SRR-CKD, Swedish Renal Registry CKD; VA CKD, Veterans Administration CKD.

Based on data from Tangri N, Grams ME, Levey AS, et al. Multinational assessment of accuracy of equations for predicting risk of kidney failure: a meta-analysis. JAMA. 2016;315:164–174.

A lower GFR has also been associated with concomitant bone, metabolic, endocrine, and hematologic abnormalities. Well-known pathophysiologic mechanisms underlie the associations of hyperphosphatemia, hyperparathyroidism, metabolic acidosis, and anemia with a lower GFR. The relationship between these abnormalities and albuminuria is less consistent, but the presence of albuminuria does appear to impart a higher risk of hyperparathyroidism and anemia over and above the eGFR.

Age is one of the strongest risk factors for the development of CKD. The prevalence of CKD stages G1 to G5 has been reported as nearly 40% in those older than 70 years and >50% in those 75 years and older in the United Kingdom. Although some have dismissed age as a risk factor, suggesting that nephron loss is a normal part of aging, ^, associations between a lower eGFR and higher albuminuria and adverse outcomes, including both death and ESKD, persisted in all subgroups of age in an individual-level meta-analysis of 2 million participants from 46 cohort studies. On the other hand, among people with stages G3 to G5 CKD, older age is associated with a lower risk for ESKD, which may be due to the higher risk of mortality, both overall and attributable to CKD at an older age. ^, The heat-map pattern of risk persisted in an updated meta-analysis of 5 Million people. ^,

Sex is also associated with CKD, although the relations are a bit nuanced. Women are at a slightly higher risk for the development of CKD stage G3; however, later stages of CKD are more common in men, suggesting that men may be at higher risk for CKD progression. ^, The relation between eGFR and albuminuria and adverse outcomes was examined by sex in an individual-level meta-analysis of 2 million participants. Men had a higher absolute risk of ESKD, death, and cardiovascular mortality at all levels of eGFR and albuminuria, but the relation between eGFR and albuminuria and adverse outcomes was similar between the sexes.

Compared with Americans of primarily European ancestry, African Americans have a much higher risk of later-stage CKD and CKD progression. These racial differences are only partially explained by differences in socioeconomic or clinical risk factors. In a nationally representative cohort of adults older than 45 years, the prevalence of an eGFRcr of <60 mL/min/1.73 m ² was 8.6% among Black individuals and 5.3% among non-Black individuals, and prevalence of eGFRcr < 30 mL/min/1.73 m ² was 1.5% among Black individuals and 0.4% among non-Black individuals when using the CKD-EPI 2021 race-free equations. The use of different estimating equations or different filtration markers results in slightly different prevalence estimates with race free equations typically resulting in higher prevalence estimates in African-American populations and lower estimates in European populations when serum creatinine alone is used and smaller differences when cystatin C information is available.

The racial disparities in CKD are explained in part by the APOL1 high-risk alleles, a genetic variant that when present in two copies confers approximately a twofold higher risk of CKD progression and ESKD. ^{, , ,} The gene variants provide resistance to infection with Trypanosoma brucei rhodesiense, a parasite endemic to Africa ( Fig. 18.8 ). The exact mechanism for increased kidney risk is uncertain, and APOL1 high-risk status—present in about 12% of African Americans but less than 1% of Whites in population-based studies in the United States —is thought to require a “second hit” to be pathogenic for kidneys. The presence of sickle cell trait, present in 7% of African Americans but virtually absent in Whites, also confers up to a twofold higher risk of ESKD, although less reliable across studies. ^, Both APOL1 high-risk status and sickle cell trait are present in greater proportions in the ESKD population than in the general population. ^,

Distribution of the G1 and G2 APOL1 variants across Africa.

Allele frequencies of the G1 and G2 variants are indicated as blue and green wedges, respectively. Circle size reflects the number of individuals genotyped: small, <10 individuals/20 chromosomes; medium, 10–100 individuals/20–200 chromosomes; large, >100 individuals/200 chromosomes. Countries are shaded according to the subspecies of Trypanosoma brucei that causes African sleeping sickness. Darker green, gambiense types 1 and 2; light green, gambiense type 1; pink, both rhodesiense and gambiense type 1; purple, rhodesiense.

From Thomson R, Genovese G, Canon C, et al. Evolution of the primate trypanolytic factor APOL1. Proc Natl Acad Sci U S A. 2014;111:E2130–E2139.

Other discovered genetic variants may also have effects on the development and progression of CKD, but they have generally had much smaller population prevalences or effect sizes than APOL1 risk alleles and the sickle cell trait. For example, genetic variation in UMOD, the gene coding for uromodulin, expressed in the thick ascending limb of the loop of Henle, may play a role in CKD. Uromodulin is the most commonly found protein in normal urine and likely affects renal salt handling. ^, Common variants in the promoter region of UMOD have been associated with increased risk of CKD, CKD progression, ESKD, and hypertension in genome-wide association studies, albeit with a difference in the rate of eGFR decline in the range of 0.15 mL/min/1.73 m ² per year. ^, Genome-wide association studies have also identified genomic regions associated with more specific disease types, such as IgA nephropathy and idiopathic membranous nephropathy. ^, Many genetic variants underlying monogenic disease have also been determined, such as variants in PKD1 or PKD2 causing autosomal dominant polycystic kidney disease and more than 20 genes involved in syndromic and nonsyndromic congenital anomalies of the kidney and urinary tract (a leading cause of kidney disease in children), but most of these genotypes are rare (<1 in 1000 for dominant diseases and <1 in 40,000 for recessive diseases). ^{, ,}

Among clinical risk factors, the presence of diabetes mellitus and hypertension appear to be the most robustly associated with CKD. The presence of diabetes mellitus was a risk factor for the development of CKD after full or partial nephrectomy and also in several community-based studies. ^, Diabetes has also been linked to the development of kidney failure and is considered the most common cause of ESKD in the world today. Evidence that tight glycemic control helps forestall the development of mild to moderate albuminuria in clinical trials further advances the notion that the presence of diabetes mellitus is on the causal pathway for the development and progression of many types of CKD. Interestingly, among people with CKD, diabetes is a weaker risk factor for ESKD once the GFR and albuminuria are accounted for since they represent mediators of the relation between diabetes and ESKD.

In contrast to the well-accepted role of diabetes in the development of CKD, there is ongoing debate as to whether hypertension is a cause of CKD, a consequence of CKD, or both. Many observational studies have linked higher blood pressure to the development and progression of CKD, but evidence from randomized controlled trials that lowering blood pressure helps forestall CKD progression is inconsistent. The Modification of Diet in Renal Disease study ( N = 840) showed no benefit of the lower blood pressure goal on GFR decline during the trial period (mean, 2.2 years) but a beneficial effect on ESKD during longer follow-up. The African American Study of Kidney Disease and Hypertension ( N = 1094) showed no benefit of the lower blood pressure goal on GFR decline over a mean of 4 years or on ESKD during longer follow-up. However, both studies suggested a larger benefit of the lower blood pressure goal in patients with higher proteinuria. ^, The REIN-2 trial did not show a difference in progression to ESKD with a lower blood pressure goal, but this study achieved the lower blood pressure goal using a calcium channel blocker. This increases proteinuria, which may have blunted any beneficial effect. In PKD, the HALT-PKD study showed a beneficial effect of a lower blood pressure goal on enlargement in total kidney volume but not on eGFR decline. In SPRINT, a lower blood pressure goal appeared to result in a lower eGFR over the first 18 months, but eGFR trajectories remained relatively stable after that time, with a large beneficial effect of lower blood pressure on death and CVD, despite the higher risk of incident CKD. The complexity of the relation of blood pressure treatment to CKD progression may not be surprising given the complex regulation of intrarenal hydraulic pressures, including by the afferent and efferent glomerular arterioles, and the central role of the kidney in regulating total blood volume, vascular resistance, and blood pressure.

Another increasingly prevalent risk factor for CKD is obesity. In a study of 320,252 participants in a U.S. health plan, obesity was associated with more than a threefold higher risk of developing ESKD over a mean of 26 years of follow-up. Contemporary studies with shorter follow-up have shown slightly more modest risks of CKD stages G4 to G5 associated with obesity, such as one in the United Kingdom, which estimated a twofold higher risk associated with body mass index (BMI) between 30 and 35 kg/m ² . Similarly, a meta-analysis of ESKD risk among >4 million potential kidney donor candidates showed a 1.16 times higher risk per 5 kg/m ² higher BMI over 30 kg/m ² . The risk of CKD progression associated with obesity may be smaller still; in one cohort of Swedish people with CKD stages G4 to G5, BMI was unrelated to subsequent ESKD. On the other hand, weight loss achieved by lifestyle modification or bariatric surgery has been associated with a reduction in albuminuria and preservation of eGFR. For example, in Look AHEAD, a clinical trial in 5145 participants with diabetes, an intensive lifestyle intervention resulted in 4 kg of weight loss compared with the control arm and a 31% reduction in the development of CKD in very-high-risk categories, as defined by KDIGO. Obesity may contribute to CKD as a risk factor mediated by the development of diabetes and hypertension or with independent causal effects. In animal models, obesity results in glomerular hypertension and hyperfiltration, a proinflammatory milieu, and reduced adiponectin levels, all of which may contribute to CKD risk.

There have been localized epidemics of kidney disease, such as Balkan nephropathy, those due to Chinese herbal supplements (now attributed to aristolochic acid ), and the more recent Mesoamerican nephropathy, which point to environmental factors that may additionally alter the risk of ESKD in populations.

In the United States, data regarding ESKD are generally excellent due to the establishment of comprehensive and well-maintained kidney disease registries by the National Institutes of Health in 1989. Today, the Annual Data Reports of the U.S. Renal Data System (USRDS) and the Scientific Registry of Transplant Recipients provide extensive epidemiologic information on incident and prevalent ESKD based on required reporting by providers of dialysis and transplantation services. As such, the epidemiology of ESKD reflects the clinical practice of initiation of KRT, as well as the progression of CKD to kidney failure. Information on untreated kidney failure—GFR < 15 mL/min/1.73 m ² not treated by KRT—is not captured by the USRDS or Scientific Registry of Transplant Recipients. Some data sources have suggested that untreated kidney failure could represent a substantial number of kidney failure cases, particularly among the very old. ^, Causes of kidney disease among those with ESKD are ascertained from the Centers for Medicare & Medicaid Services Form 2728 but are frequently missing and have not been validated. Because dialysis is the predominant mode of KRT, the epidemiology of ESKD largely reflects the epidemiology of dialysis. Specific topics related to the epidemiology of kidney transplantation are covered in a separate section.

As of December 31, 2020, there were 807,920 prevalent cases of ESKD in the United States or a rate of 2271/million population. Both figures decreased slightly over the preceding year, for the first time in 2 decades. For reference, in 2000, the number of cases of ESKD was 389,592, or 1581 cases/million population ( Fig. 18.9 ). Much of the growth in prevalence was attributable to the aging of the population (ESKD is more common in older populations) and growth in ESKD in those aged 75 years and older, in whom the sex- and race-adjusted prevalence of ESKD increased from 4639/million population in 2000 to 7172/million population in 2020. The growth in prevalence is also partly due to a decline in mortality, which decreased from 149/1000 patient-years to 133 deaths/1000 patient-years in 2019, although there was a large uptick presumably attributable to COVID in 2020.

Trends in adjusted ESKD prevalence (per million; trend lines; scale on left) and annual percentage (%) change in adjusted prevalence of ESKD ( vertical lines; scale on right) in the U.S. population, 2000-2020, adjusted for age, sex, race, and ethnicity.

The standard population was the U.S. population in 2015.

Data from U.S. Renal Data System. 2022 USRDS annual data report: epidemiology of kidney disease in the United States.

In the United States, approximately 70% of prevalent ESKD cases were treated by dialysis, either hemodialysis (59.8%) or peritoneal dialysis (8.1%). The majority of ESKD cases were attributed to diabetes or hypertension, followed by glomerulonephritis and cystic kidney disease.

In 2022, the USRDS collected ESKD data from 49 different countries, enabling comparisons of both the absolute counts of ESKD cases and prevalence per million population. The prevalence of ESKD within the population varied substantially across the participating country, ranging from 109 per million population in Bangladesh to 3772 cases per million population in Taiwan. The Republic of Korea had the second highest prevalence, at 2708 per million population. All countries providing annual data since 2010 ( N = 45) showed increases in prevalence (median, 19.6%). The increase was greatest in Thailand and the Republic of Korea, where the percent changes from 2010 to 2020 were 174% and 136%, respectively.

Large variations also existed among countries with respect to the distribution of KRT modality ( Fig. 18.10 ). In Iceland, 71% of prevalent ESKD patients were treated with a functioning transplant, 24% received in-center hemodialysis, and 6% received peritoneal dialysis in 2020. Peritoneal dialysis was most common in El Salvador, where 64% received peritoneal dialysis and 35% received in-center hemodialysis. In contrast, in-center hemodialysis comprises ≥95% of the ESKD in Japan and Montenegro. Additional information on differences in hemodialysis practice by country was collected by the Dialysis Outcomes and Practice Patterns Study between June 1996 and March 2012. Interestingly, in the population of 35,964 hemodialysis patients sampled from 12 countries, the proportion of women was much lower than that of the general population. This appeared attributable to a greater incidence of ESKD among men rather than better survival because the male-to-female mortality ratio was close to 1.

Percentage distribution of type of kidney replacement therapy modality used by patients with end-stage kidney disease. By country, in 2020.

HD, Hemodialysis.

From U.S. Renal Data System. 2022 USRDS annual data report: epidemiology of kidney disease in the United States.

Evidence suggests that the variation in ESKD prevalence has much to do with the resources available to provide KRT. One study has suggested that the gap between people worldwide who require KRT and those who undergo KRT was at least 2.3 million in 2010. The authors estimated the prevalence of ESKD undergoing KRT to be 1839 cases/million people in North America, followed by 719 cases/million people in Europe, 686 cases/million in Oceania, and 626 cases/million in Latin America. Asia, which was reported to have an ESKD prevalence of 232 cases/million population, was estimated to have the highest absolute number of people with ESKD, at nearly 1 million cases in 2010. Gross national product was highly associated with prevalence, with the highest-income countries reporting a much higher prevalence of patients undergoing KRT. Interestingly, this relationship was much stronger than the one between the prevalence of diabetes and prevalence of patients undergoing KRT ( Fig. 18.11 ). The International Society of Nephrology Global Kidney Health Atlas provides a detailed summary of the variation in access to KRT, ranging from 40% in Africa in 2023 to 100% in Europe, the Middle East, and North and East Asia. ^,

Association between prevalence of end-stage kidney disease (ESKD) treated by dialysis in 123 countries (gross national income per capita [left], prevalence of diabetes [right]).

In both graphs, China and India are represented by the largest and second largest circles, respectively.

From Liyanage T, Ninomiya T, Jha V, et al. Worldwide access to treatment for end-stage kidney disease: a systematic review. Lancet . 2015;385:1975–1982.

The incidence, or rate of new cases, of ESKD is also reported annually by the USRDS. In the United States, the number of incident cases of ESKD in 2020 was 130,522, or an incidence rate of 393 per million per year. These figures are 3.3% and 6.2% decreases, respectively, over the prior year. However, since 2000, the trend has been a relatively steady increase: The number of incident cases of ESKD was 94,466, or 330 cases per million population. Much of this increase in incidence rates can be attributed to aging of the U.S. population.

Most of the new ESKD cases initiated KRT using hemodialysis (83.9%), whereas 12.7% used peritoneal dialysis and 3.1% received a kidney transplant without prior dialysis. These proportions have remained relatively stable over the past decade. The adjusted incidence rate for Black/African American individuals was 949 cases per million persons in 2020, down from 1135 per million persons in 2000. Declines were also seen in the Native American population (893 to 596 cases per million persons) and U.S. Hispanic population (695 to 511 cases per million persons). In contrast, the adjusted incidence of ESKD within Asian and White populations was relatively flat over the past 2 decades (371 to 349 cases per million persons and 270 to 249 cases per million persons, respectively).

When extended to estimate the lifetime incidence of ESKD, racial and ethnic disparities remain. ^{, ,} One study using 2013 USRDS data has suggested that the lifetime incidence of ESKD is 3.1% for a non-Hispanic white man, 6.2% for a Hispanic man, and 8.0% for a non-Hispanic Black man. Furthermore, these disparities changed little over the previous decade.

When compared with other countries, the incidence of ESKD in the United States was among the highest, trailing only Taiwan in 2020. Other high ESKD incidence countries included Singapore, the Republic of Korea, Thailand, Japan, and Indonesia. Among the represented countries, the lowest incidence rate per million population/year was in South Africa with 11 ESKD cases per million per year. Trends in the incidence of ESKD varied by country, with many of the Northern European countries experiencing lower ESKD incidence over time. In contrast, there were large increases in incidence rates in Thailand, the Republic of Korea, Indonesia, and Mexico ( Fig. 18.12 ).

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