INTRODUCTION — The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines define chronic kidney disease (CKD) as abnormalities of kidney structure or function for more than three months [1]. The classification of CKD is based upon the cause of CKD (C), glomerular filtration rate (GFR; G; categories G1 to G5), and albuminuria (A; categories A1 to A3) (table 1). This classification also includes treatment for kidney failure (ie, GFR <15 mL/min/1.73 m2) with kidney replacement therapies (KRT), such as dialysis (CKD G5D) or transplantation (CKD G1T to G5T), and kidney failure without replacement therapy, with either comprehensive or choice-restricted conservative care [1].
The classification of CKD is related to associated risks of various complications, such as mortality, cardiovascular disease, and kidney failure (figure 1 and figure 2) [2].
The epidemiology of CKD is presented in this topic. The definition, staging, evaluation, and treatment of CKD are discussed in other topics:
●(See "Definition and staging of chronic kidney disease in adults".)
●(See "Chronic kidney disease (newly identified): Clinical presentation and diagnostic approach in adults".)
●(See "Overview of the management of chronic kidney disease in adults".)
GLOBAL BURDEN OF CKD — According to the Global Burden of Disease (GBD) study in 2017, there were 698 million recorded cases of CKD (95% CI 649-752) for an estimated global prevalence in the adult population of 9.1 percent (8.5 to 9.8) [3]. Of this, CKD G1 to G2 accounted for 5 percent, G3 for 3.9 percent, G4 for 0.16 percent, G5 for 0.07 percent (not including patients on dialysis or transplant recipients), dialysis for 0.04 percent, and kidney transplantation for 0.01 percent. However, based on a meta-analysis of 100 studies (6,980,440 patients), the global CKD prevalence could be as high as 13.4 percent (11.7 to 15.1), with a prevalence of CKD stages 3 to 5 of 10.6 percent (9.2 to 12.2) [4].
In the GBD study in 2017, the age-standardized prevalence of CKD was 1.29 (1.28 to 1.30) times higher in females (9.5 percent [8.8 to 10.2]) than in males (7.3 percent [6.8 to 7.9]). However, the age-standardized incidence of dialysis and transplantation was 1.47 (1.46 to 1.48) times higher among males (13.7 percent [12.6 to 14.9]) than among females (8.6 percent [7.9 to 9.3]). Males are more likely to start kidney replacement therapy (KRT) partly owing to faster CKD progression [5,6].
The estimated year to year variations in CKD prevalence from 1990 to 2017 were small, at around 1.2 percent change per year (1.1 to 3.5). Notwithstanding, CKD prevalence has increased by 29.3 percent (26.4 to 32.6) in this period [3].
Altogether, between 1990 and 2017, 1.4 million deaths (1.2 to 1.6 deaths) were attributable to kidney disease. Globally, the CKD mortality rate has increased by 41.5 percent (35.2 to 46.5) during this period. In parallel, the CKD worldwide ranking rose from the 17th leading cause of death in 1990 to the 12th in 2017. The global age-standardized CKD mortality rate was 1.39 (1.28 to 1.30) times higher in males (18.9 per 100,000 population [17.9 to 19.5]) than in females (13.6 per 100,000 population [13.3 to 14.0]) [3].
CKD accounted for 7.3 million (5.4 to 9.2) years lived with disability (YLDs), 28.5 million (27.6 to 29.3) years of life lost (YLLs), and 35.8 million (33.7 to 38.0) disability-adjusted life-years (DALYs). Disproportionately to other stages, G5 (ie, estimated glomerular filtration rate [eGFR] <15 mL/min/1.73 m2) or D (dialysis) accounted for most YLDs at 40 and 22 percent, respectively [3].
Regional disparities in CKD burden — In 2017, China and India accounted for one-third of the global CKD burden, with 132.3 (121.8 to 143.7) and 115.1 (106.8 to 124.1) million cases, respectively. Bangladesh, Brazil, Indonesia, Japan, Mexico, Nigeria, Pakistan, Russia, the United States, and Vietnam had more than 10 million CKD cases. Seventy-nine of 195 countries included in the GBD study had more than 1 million prevalent CKD cases [3].
Compared with the relative increase in the global age-standardized mortality rate of 41.5 percent, some countries of Central America and Asia have had disproportionally high increases in CKD mortality between 1990 and 2017 (by 60.9 percent [52.7 to 66.2] and 60.9 percent [53.3 to 68.9], respectively). In these countries, CKD ranked second and fifth as the leading cause of death, respectively. Interestingly, the age-standardized mortality rate in North America, a high-income region, is also high at 57.3 percent (53.4 to 61.1) [3].
Age-standardized DALY rates varied more than 15-fold among countries. In 2017, the highest rates, at ≥1500 DALYs per 100,000 population, were in American Samoa, El Salvador, Federated States of Micronesia, Marshall Islands, and Mauritius. The lowest, at <120 per 100,000 population, were in Andorra, Finland, Iceland, and Slovenia [3].
North America — In the United States, the US Renal Data System and the Centers for Disease Control CKD Surveillance System track kidney disease burden based on several sources of information, including the National Health and Nutrition Examination Survey (NHANES). In the latest report (2015 to 2016), CKD prevalence was 14.2 percent (12.5 to 16.0), which corresponds to approximately 31 to 34 million noninstitutionalized United States civilian residents aged 20 years or older. Of these, 15 to 18 million had evidence of CKD G3 or G4 [7]. Between 2001 and 2016, CKD G3 slightly increased from 6.1 to 6.4 percent. The rest had no significant changes over this period. A2 to A3 prevalence increased from 8.8 percent (2009 to 2012) to 10.1 percent (2013 to 2016). During this period, 8.6 percent of NHANES participants with eGFR >60 mL/min/1.73 m2 had evidence of albuminuria. Based on prognosis, the prevalence of moderate-, high-, and very high-risk categories has increased from 14.2 percent between 2001 and 2004 to 14.8 percent in 2013 to 2016. In the latter, the risk categories were [8]:
●Low risk – 85.1 percent
●Moderate risk – 10.7 percent
●High risk – 2.7 percent
●Very high risk – 1.4 percent
In Canada, based on a large cross-sectional study (559,745 participants) between 2010 and 2015, CKD prevalence was 71.9 per 1000 individuals, with a significant geographic variation. The highest reported prevalence was in rural compared with urban settings (86.2 versus 68.4 per 1000, respectively). Approximately 7.4 percent had CKD G3 to G5, without differences between sex. However, CKD prevalence rose from 29.2 to 244.6 per 1000 individuals in people aged 46 to 59 and 70 to 74. However, CKD prevalence slightly declined from 53.4 (2010) to 46.5 per 1000 over the study period (2014) [9]. Indigenous populations (First Nations) had a twofold higher CKD prevalence (25.5 percent) compared with the general population. Furthermore, the prevalence of severely increased albuminuria was fivefold higher. Both metrics are comparable to patients with diabetes and/or hypertension [10].
Latin America — Based on data from The Latin American Society of Nephrology and Hypertension (SLANH) registry and the GBD study, the Latin American (LA) region has the highest mortality rate from CKD and is second place in YLLs [3,11]. Data from the SLANH suggest that diabetes could be the primary cause for 36 to 70 percent (Mexico and Puerto Rico) of patients with CKD receiving KRT. Moreover, some countries have a CKD hotspot termed Mesoamerican nephropathy. (See "Mesoamerican nephropathy".)
Information regarding CKD prevalence and risk of progression (including risk factors) is scarce and even nonexistent in some LA countries. In 2008, based on extrapolated data from the NHANES III, there could have been up to 49,989,171 CKD cases in LA, predominantly in stages G1 to G3 and lesser in G4 to G5 (996,832). In Mexico, a population-based cross-sectional study of 3961 adults documented albuminuria in 8.7 percent of those with eGFR <60 mL/min/1.73 m2 and up to 12.5 percent among those with prior diabetes and hypertension history. By extrapolating these findings to the whole Mexican population, CKD prevalence, defined as eGFR <60 mL/min/1.73 m2, was 80,788 cases per million population (pmp), with 1142 cases pmp with eGFR <15 mL/min/1.73 m2. In comparison, data from a National Health Survey in Chile estimated that 20.97 percent of the surveyed sample had an eGFR <80 mL/min/1.73 m2 and 0.18 percent <15 mL/min/1.73 m2 [12]. Like the European experience, reviewed later, there is variability in CKD prevalence across LA countries though more data are needed to explain the cause for these differences.
Europe — The European CKD Burden Consortium, which in 2016 included 13 European countries, reported significant geographic variation in CKD prevalence (G1 to G5) in the adult population, ranging from 3.31 percent (3.30 to 3.33) in Norway (Trondelag Health Study [HUNT] study) to 17.3 percent (16.5 to 18.1) in Germany (Study of Health in Pomerania [SHIP] study) [13]. Among patients with diabetes, these estimations rose to 14.1 percent (12.0 to 16.2) in the Netherlands (LifeLines study) to 39.7 percent (34.7 to 44.8) in Germany (SHIP study). Furthermore, the adjusted prevalence of CKD G1 to G5 in the general population aged 45 to 74 years ranged from 6.3 percent in Norway to 25.6 percent in Germany. Differences in the prevalence of diabetes, hypertension, and obesity in the general population do not fully explain this variation in CKD prevalence among the different countries [13]. Other reasons for the regional variation are detailed below. (See 'Shortcomings in published estimates of CKD prevalence' below.)
Other relevant findings include:
●The Berlin Initiative Study, a population-based cohort study, estimated a higher prevalence of a GFR <60 mL/min/1.73 m2 among adults >70 years depending on the GFR estimating equation used: BSI1 (61.7 percent), Cockcroft–Gault (55.9 percent), and Lund–Malmö (55.3 percent) equations [14].
●A population-based cross-sectional study of >6000 healthy males and females in the Netherlands found that 42 percent of males and 44 percent of females >85 years of age had a Modification of Diet in Renal Disease (MDRD) eGFR <60 mL/min/1.73 m2 [15].
●Among adults in Iceland, the prevalence of eGFR <60 mL/min/1.73 m2 and albuminuria was 5 and 2 percent among males, respectively, and 12 and 1 percent among females, respectively [16].
●Based upon data from the Nord-Trondelag County, Norway (HUNT II) study, the overall prevalence of CKD in Norway, as defined by KDOQI criteria, was 10.2 percent, which is similar to that reported in the United States [17]. However, the relative risk for progression from CKD stages 3 or 4 to kidney failure was 2.5 among White American patients compared with Norwegian patients. This finding suggests that lower progression to kidney failure rather than a smaller pool of individuals at risk accounts for the lower incidence of kidney failure in Norway [13]. An updated result from this cohort in 2016 reported a drop in CKD prevalence to 3.31 (3.30 to 3.33) from 10.2 percent in 1997 [13].
Asia — North and East Asia include mainland China (including Hong Kong), Japan, Mongolia, North Korea, South Korea, and Taiwan. CKD prevalence among the adult population is lowest in mainland China (10.8 percent) and highest in Mongolia (13.9 percent). Taiwan, Japan, and South Korea are at 11.9, 12.9, and 13.7 percent, respectively. CKD patients in China are predominantly in earlier stages, with albuminuria as a sole indicator [18].
Other relevant findings include:
●One study from Japan calculated the creatinine clearance using the Cockcroft-Gault equation among nearly 100,000 subjects >20 years of age who participated in a mass screening [19]. Based upon KDOQI definitions, >80 percent of those >70 years of age would have at least CKD G3.
●In a population-based study in Korea, the prevalence of moderately increased albuminuria was 2.8 percent among normotensive, normoglycemic individuals, and 10 and 16 percent among hypertensives and diabetics, respectively [20]. In another population-based study of Korean adults aged 20 years or older, the overall CKD prevalence was 8.2 percent [21].
●In a population-based study from West Malaysia, the CKD prevalence was 9 percent [22].
●In Australia, based on the National Prescribing Service (NPS) MedicineWise's MedicineInsight and the Australian Health Survey, that assessed 29 practices and 1,483,416 patients distributed across Australia from June 1, 2013 until June 1, 2016, CKD prevalence was G1 0.45 to 3.9, G2 0.62 to 2.5 percent, G3a 3.1 to 2.7 percent, G3b 0.6 to 1.14 percent, and G4 to G5 0.3 to 0.41 percent [23].
Africa — Based on a meta-analysis of 98 studies (98,432 participants), the overall CKD prevalence in Africa is 15.8 percent (95% CI 12.1–19.9), with CKD G3 to G5 accounting for 4.6 percent (3.3 to 6.1) of the general population. Compared with North Africa, Sub-Saharan Africa had a significantly higher CKD prevalence (17.7 percent [13.7 to 22.1] versus 6.1 percent [3.6 to 9.3]) [24].
Shortcomings in published estimates of CKD prevalence — As previously described, CKD prevalence varies regionally, even within countries. As an example, the regional variation across 27 European countries in CKD prevalence ranged from 3.31 percent (3.30 to 3.33) in Norway to 17.3 percent (16.5 to 18.1) in Germany. Reasons for these variations are manifold but may include actual regional differences or may stem from issues related to GFR estimation (eg, type of equation used), cut-off thresholds (especially among older adults), or one-off testing assessments in several large-scale reports. The latter is particularly relevant because failure to adhere to the >3-month duration criteria of the Kidney Disease: Improving Global Outcomes (KDIGO) definition can lead to the overestimation of CKD prevalence and high false-positive rates. Indeed, false positives may be as high as 30 percent when using eGFR and even higher for albuminuria. More often, false positives from one-off testing reports can arise when assessing young or older adult individuals and people with chronically low or high protein intake, among others [25].
Inulin urinary clearance is the current gold-standard for GFR determination, but this approach is too costly and cumbersome (requires an intravenous continuous infusion and plasma samples over many hours). Plasma clearance of iothalamate or iohexol has been used as an alternative in large studies, eg, Chronic Renal Insufficiency Cohort (CRIC; n = 1214), the Berlin Initiative Study (BIS; n = 570), the Age, Gene/Environment Susceptibility (n = 805), and the Renal Iohexol Clearance Survey (RENIS; n = 1,632) studies [25].
The effect of ancestry is crucial in GFR estimation with the MDRD or CKD-EPI equations. For African American individuals, the proposed coefficient factor of 1.21 and 1.15 has been criticized for cases with normal GFR and Africans outside the United States. Notwithstanding, without correction, the eGFR would yield 21 or 15 percent higher rates, respectively. The latter might partly explain the disparity in CKD and kidney failure prevalence. Compared with White Americans, African Americans have lower CKD prevalence but higher rates of kidney failure. For Asians, there are several proposals for correction factors. Hence, some of the CKD prevalence across these populations might be under or overestimated [25].
An approach that might decrease the effect of ancestry on eGFR determination is a cystatin C‑based equation, since cystatin C does not seem to be influenced by ethnicity [25]. In the general population and the older adult population, eGFR determination with cystatin C might be a useful predictor of adverse cardiovascular events and mortality. However, its clinical use has not been well established, but may identify CKD patients at the highest risk for complications compared with serum creatinine [25]. (See "Assessment of kidney function".)
CKD hotspots — CKD hotspots have been defined as countries, regions, communities, or ethnicities with a higher than average incidence of CKD. Although specific etiologic factors have not yet been identified, most cases are due to nontraditional causes of CKD, such as infections and CKD of unknown etiology. CKD hotspots have been described in several regions of the world, including some Central American countries (the so-called Mesoamerican nephropathy), the Balkan nations, Sri-Lanka, Andhra Pradesh in India, the northern region of Australia, and some areas of New Zealand and the Pacific Islands. The premature death and disability toll in most CKD hotspots are enormous, partly due to lack of access to health care and KRT, and insufficiently trained personnel, among other factors. As an example, El Salvador has the highest mortality rate from kidney disease at a global level, and CKD is the second leading cause of death among Salvadoran males of working age [26,27]. (See "Mesoamerican nephropathy".)
KIDNEY FAILURE — Despite preventive strategies (ie, diet and lifestyle changes, glycemic control, nephroprotection with angiotensin-converting enzyme inhibitors), approximately 0.1 percent of the world population has kidney failure (ie, end-stage kidney disease), and over 90 percent in low and low-middle income countries remain untreated. Prevalence is reportedly higher among upper-middle (0.1 percent) and high-income (0.2 percent) compared with low (0.05 percent) or lower-middle (0.07 percent) income countries [28]. Data from a meta-analysis of 13 renal registries and 123 countries (93 percent of the world population) indicated that, in 2010, 2.6 million people received some form of kidney replacement therapy (KRT), predominantly dialysis (78 percent) rather than transplantation. However, this study estimated that the need for KRT extended to at least 4.9 million individuals (95% CI 4.4–5.4), and perhaps as many as 9.7 million (8.5 to 11.0). The latter suggests that approximately 2.3 million people might have died prematurely due to a lack of KRT access. More importantly, worldwide demand for KRT is projected to double to 5.4 million (3.9 to 7.6 million) between 2010 and 2030, driven predominantly by increased demand in Asia [28,29].
Similarly, kidney failure and KRT prevalence vary widely within and across geographic regions up to 1000-fold [30]. The largest KRT cases were in high-income countries from Asia (0.968 million) and North America (0.637 million). The most significant treatment gaps, cases needing but not on KRT, were in low-income countries from Asia (1.907 million) and Africa (432,000 people) [28,29].
Trends in kidney failure — Kidney failure projections are needed to aid in planning future patient needs. In the United States, the incidence of kidney failure is projected to increase by 11 to 18 percent by 2030, owing in large part to changes in age, race distribution, obesity, and diabetes prevalence. Kidney failure prevalence is similarly expected to increase by 2030, by 29 to 68 percent (or 971,000 to 1,259,000 individuals), due in large part to increasing incidence combined with improved survival [31].
●Taiwan, Mexico (State of Jalisco), and the United States continue to report the highest incidence of treated kidney failure (458, 421, and 363 per million population, respectively) [8].
●The greatest increases in incidence between 2000 and 2012 were in Thailand (1210 percent), Bangladesh (629 percent), Russia (249 percent), Philippines (185 percent), Malaysia (176 percent), Mexico (State of Jalisco) (122 percent) and the Republic of Korea (120 percent) [8].
●In 2013, more than 50 percent of incident kidney failure cases were due to diabetes in Malaysia, Singapore, and Mexico (State of Jalisco), and less than 20 percent in Norway, the Netherlands, Iceland, and Romania [8].
●The steepest increases in kidney failure incidence due to diabetes from 2000 to 2013 were in Thailand, Russia, Philippines, Malaysia, the Republic of Korea, Mexico (State of Jalisco), and Uruguay [8].
Kidney replacement therapies — The availability of KRTs has grown worldwide. Between 1990 and 2017, the global all-age incidence of dialysis and kidney transplantation increased by 43.1 percent (40.5 to 45.8) and 34.4 percent (29.7 to 38.9), respectively [3]. However, despite this growth, the availability of KRT is still limited in many parts of the world, particularly in low- and middle-income countries that have a high incidence of CKD.
A study from 2003 to 2005 of 46 countries (1.25 billion adults) showed variability in KRT incidence from 12 per million population (pmp) in Bangladesh to 455 pmp in Taiwan, with a median KRT incidence of 130 pmp [32]. According to the US Renal Data System, of 661,000 adults with kidney failure, 468,000 individuals (71 percent) received dialysis. However, compared with White individuals, African American individuals had a lower implementation of in-home dialysis strategies (including home hemodialysis and peritoneal dialysis; 6.4 versus 9.2 percent) [33].
Access to KRT is reportedly higher in developed regions compared with developing nations [5]. North America, Europe, Chile, Uruguay, Japan, South Korea, and Thailand have the highest prevalence of treated kidney failure per 1 million population [5]. Increasing access to KRT faces several key challenges (especially in low- to middle-income countries), including high costs, lack of trained medical personnel and infrastructure, and disparities in health care provision [5,6].
Peritoneal dialysis — In 2008, in an observational study from 122 countries, there were 196,000 peritoneal dialysis patients worldwide, which constituted 11 percent of the total dialysis population. Approximately 59 percent were treated in developing and 41 percent in developed countries. From 1997 to 2008, the number of peritoneal dialysis patients increased in developing countries by 24.9 patients pmp and developed countries by 21.8 pmp. However, the peritoneal dialysis rate declined in developed countries by 5.3 percent over the follow-up period. In total, globally, the number of people treated with peritoneal dialysis increased 2.5-fold in developing countries but continued to decline in developed countries [34].
Between 2000 and 2013, the highest utilization of peritoneal dialysis was found in Hong Kong (72 percent), Mexico (State of Jalisco) (45 percent), Iceland (34 percent), New Zealand (32 percent), Colombia (30 percent), and Thailand (25 percent) [8].
While peritoneal dialysis use is increasing in some countries, such as China, Thailand, and the United States, it has decreased in parts of Europe and in Japan [35]. In 2009, no dialyzed patients were on peritoneal dialysis in Switzerland. However, by 2014 its adoption rose to 5 percent [36].
Australia, China, Hong Kong, Mexico, New Zealand, Thailand, and the United States have implemented public policies to promote peritoneal dialysis utilization through financial incentives. Some of these countries have implemented peritoneal dialysis-first policies to reduce costs and improve access. Compared with hemodialysis, peritoneal dialysis requires less infrastructure and can cost-effectively be scaled up by manufacturing dialysate fluids locally [37]. Despite peritoneal dialysis being cheaper than hemodialysis, most patients are still receiving hemodialysis. Factors contributing to low peritoneal dialysis utilization may include clinician and patient preference, patient comorbidities, greater experience with hemodialysis, late referral to nephrology, and clinician remuneration, among others. However, hemodialysis services tend to be located in larger cities and are often paid out of pocket [37].
Hemodialysis — Hemodialysis is the dominant form of KRT and accounts for 80 to 90 percent of all dialysis. A study by the International Society of Nephrology Global Kidney Health Atlas (GKHA) Project 2019 found that hemodialysis is available in 93 percent of countries, and in-center hemodialysis remains the most frequent treatment modality for kidney failure [29].
Globally, hemodialysis to peritoneal dialysis utilization ratios vary, particularly in countries where public and private sectors exist. In 2013 in South Africa, the hemodialysis/peritoneal dialysis ratio for the public sector was 48/26 percent versus 84/8 percent in the private sector [29,37].
Mortality for hemodialysis patients is markedly higher than the general population. Compared with matched general population controls, the mortality rate of hemodialysis-treated individuals is 12.6 (95% CI 10.8-14.6) [38] (see "Dialysis modality and patient outcome").
Among patients receiving hemodialysis, mortality rates are lower among Black patients as compared with White patients. The reasons for this observation are unclear [33].
Transplantation — In 2014, 80,000 kidney transplants were performed worldwide although this covered only 10 percent of the total need [39]. Rates of kidney transplantation are higher in high-income countries (ie, performed in 50 percent of treated kidney failure patients). According to the Global Observatory on Donation and Transplantation, kidney transplantation is nonexistent in most of Africa and some countries of Southeast Asia. Specifically, Africa had a transplant rate of 0.4 pmp in 2015 because many countries did not have transplant programs. The United States, France, and Spain have the highest rates at 52 to 63 pmp worldwide [30].
Living donor kidney transplantation rates seem equal between males and females [5,6].
The incidence of pre-emptive kidney transplantation (before the onset of dialysis) is highest in the United States, the United Kingdom, and Norway (>6.9 pmp), followed by Canada, France, Spain, Sweden (5.2 to 6.9), and Australia and New Zealand (<1.5). Most countries in the GKHA initiative do not have data or do not offer pre-emptive transplantation [28].
In 2013, the kidney transplantation rates relative to population size were higher in Croatia (59 pmp), Mexico (State of Jalisco) (58 pmp), the Netherlands (56 pmp), the United States (56 pmp), and Spain (54 pmp) [8].
Between 2000 and 2001, the largest absolute increases in kidney transplant rate occurred in the following countries: Croatia (from 9 to 59 pmp), the Netherlands (from 36 to 56 pmp), the Republic of Korea (from 14 to 34 pmp), Scotland (from 36 to 51 pmp), Turkey (from 6 to 38 pmp), and Uruguay (from 17 to 32 pmp) [8].
Conservative care (without kidney replacement therapy) — Conservative care is planned, holistic, patient-centered care for patients with G5 CKD. It includes interventions to delay kidney disease progression, minimize the risk of adverse events and complications, and active symptom management; clear communication, including advance care planning and shared decision-making; and psychosocial and spiritual support for patients and their families. Specifically, conservative care does not include dialysis. It can be either comprehensive for patients who elect not to start KRT or who are medically advised not to start KRT based on their circumstances, or choice-restricted for whom resource constraints prevent or limit access to KRT [40].
To date, there is limited evidence on the prevalence and incidence of conservative care. Most international registries report the prevalence of kidney failure and cases receiving KRT. Based on a community cohort study in Canada of 1,816,824 adult patients, only 0.17 percent received conservative care [41]. However, data from the GKHA suggest that all countries in North, East, and South Asia, and most countries in eastern and central Europe (95 percent, 18/19 countries), Oceania and Southeast Asia (93 percent, 14/15 countries), western Europe (90 percent, 18/20 countries), the Middle East (82 percent, 9/11 countries), and Africa (80 percent, 33/41 countries), offered conservative care [6]. Older females are more likely to choose conservative care and have reduced access to deceased donor transplantation than males, perhaps due in part to higher allosensitization associated with pregnancy [5,6].
Incidence of CKD — There are limited data concerning the incidence of new-onset CKD:
●The Framingham Offspring study consisted of 1223 males and 1362 females who were initially free of pre-existing kidney disease [42]. After a mean follow-up of 18.5 years, 244 participants (9.4 percent) had developed kidney disease (defined as Modification of Diet in Renal Disease [MDRD] estimated glomerular filtration rate [eGFR] of <64 and 59 mL/min/1.73 m2 for males and females, respectively). The development of CKD was associated with increased age, diabetes, hypertension, smoking, obesity, and lower baseline glomerular filtration rate [GFR].
●In a retrospective cohort study over 5.5 years of follow-up, the estimated annual incidence of CKD (defined as serum creatinine ≥1.7 mg/dL [150 micromol/L] for six months or longer) was 1700 pmp [42].
INCIDENCE OF KIDNEY FAILURE — There are limited data on kidney failure progression. Some trends reported in the literature include:
●United States – In 2017, African Americans accounted for 30 percent of incident kidney failure cases. Compared with White Americans, Black Americans have a 3.7-fold increased prevalence rate of kidney failure. The latter, despite increased access to patient-centered home dialysis, preemptive kidney transplantation, and decreased mortality. Based on the Multiple Risk Factor Intervention Trial, lower-income and/or socioeconomic status correlate with excess risk of kidney failure among African American males compared with White American males (3.20 to 1.87, 95% CI 1.47–2.39) [33].
●Switzerland – Increases in the age-adjusted incidence of kidney failure among adults younger than 60 years have been predominantly driven by increases in renal vascular disease and type 2 diabetes. The joint prevalence of diabetes and kidney failure rose from 38 percent in 2009 to 47 percent in 2014 [36]. This increase also mirrored an increase in KRT. During the same period, kidney failure incidence due to glomerulonephritis, interstitial nephritis secondary to a urological cause, and type 1 diabetes decreased. Similar trends were also reported in the Netherlands [43].
Apolipoprotein L1 in African Americans — Genetic factors underlie, at least in part, the markedly increased risk of kidney failure among African Americans. Two different disease-causing polymorphisms, believed initially to reside in the podocyte nonmuscle myosin IIA gene but now known to be located in the neighboring apolipoprotein L1 (APOL1) gene [44-47], follow an autosomal recessive pattern of inheritance and confer a substantially higher risk of kidney failure (10-fold higher risk of kidney failure due to focal glomerulosclerosis and a sevenfold higher risk of kidney failure attributed to hypertension) [47-51].
APOL1 mutations are also associated with an earlier onset of kidney disease. In a study of 407 African American patients receiving hemodialysis, patients with two mutant alleles were significantly younger at the time of dialysis initiation than those without any disease-causing APOL1 mutation (49 versus 62 years) [52]. Also, these polymorphisms are associated with earlier stage CKD. In a population-based study that included 1776 African Americans without known kidney disease (mean age 45 years), homozygotes for APOL1 mutations were more likely to have moderately increased albuminuria (formerly called "microalbuminuria;" 18 versus 9 percent) and an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 (6 versus 3 percent) compared with other individuals [50].
Among patients who have CKD, high-risk APOL1 alleles are associated with a more rapid decline in eGFR. In posthoc analyses of the Chronic Renal Insufficiency Cohort (CRIC) study, 2955 patients (48 percent were Black patients and 46 percent were patients with diabetes) were analyzed by race and according to the absence or presence of high-risk APOL1 alleles [51]. Over a mean follow-up of 4.4 years, the eGFR declined faster among Black patients with a high-risk APOL1 allele than Black patients with a low-risk APOL1 allele and White patients. This association was observed among diabetic patients (with declines in eGFR of -4.3 versus -2.7 and -1.5 mL/min/1.73 m2 per year, respectively) and nondiabetic patients (-2.9 versus -1.0 versus -0.7 mL/min/1.73 m2 per year, respectively).
APOL1 mutations are found exclusively among individuals of African descent and, although speculative, are believed to provide resistance to disease-causing trypanosomes. The functional significance of these gene variants is unclear, but they may lead to diminished expression of APOL1 in podocytes and inappropriate expression in renal arterioles [53].
The association of APOL1 polymorphisms with specific kidney diseases is discussed separately. (See "HIV-associated nephropathy (HIVAN)" and "Clinical features, diagnosis, and treatment of hypertensive nephrosclerosis" and "Collapsing focal segmental glomerulosclerosis not associated with HIV infection" and "Focal segmental glomerulosclerosis: Epidemiology, classification, clinical features, and diagnosis".)
Impact of CKD and kidney failure on morbidity and mortality — Early stages of CKD as well as kidney failure are both associated with high morbidity and increased health care utilization. Approximately 50 percent of dialysis patients have three or more comorbid conditions; the number of hospitalizations and hospital days are 1.9 and 12.8 per patient-year, respectively, and self-reported quality of life is far lower in dialysis patients than in the general population [54-57].
The adverse outcomes observed among patients with kidney failure are also reported among those with earlier stages of CKD and are driven by many of the same risk factors, although the magnitude of the excess risk as compared with the general population is lower for those with milder CKD. As an example, in a retrospective analysis of 259 adult patients with CKD (defined as serum creatinine ≥1.5 mg/dL [133 micromol/L] for females and ≥2 mg/dL [177 micromol/L] for males), hypertension, diabetes, cardiovascular disease (CVD), and peripheral vascular disease were present in 87, 35, 40, and 14 percent, respectively [58]. Forty-seven percent of patients were hospitalized during a median follow-up of 11.4 months, and the number of hospitalizations and hospital days per patient-year at risk were 0.96 and 6.6, respectively. CVD (excluding congestive heart failure) and hypertension were the most common primary diagnoses, accounting for 24.5 percent of hospitalizations. In a multivariable regression analysis, older age and presence of cardiac disease were associated with higher risk of hospitalization, while higher albumin and higher hematocrit levels were associated with lower risk of hospitalization.
The results of this study highlight some general observations concerning early stages of CKD and kidney failure:
●The prevalence of certain comorbid conditions among patients with earlier stages of CKD were comparable to the prevalence of these conditions in the United States dialysis population: CVD (40 versus 59 percent for dialysis patients), cerebrovascular disease (12 versus 8 percent), and peripheral vascular disease (14 and 14 percent) [59].
●The causes of hospitalization were similar to those in the United States dialysis population, with the exception of vascular access hospitalizations [59,60].
●The rates of hospitalization and of hospital days per patient-year at risk were three times higher among patients with earlier stages of CKD than in the general population and approximately one-half when compared with those of dialysis patients [61,62].
●Risk factors for hospital utilization were similar to those observed among kidney failure patients, such as older age, gender, race, cardiac disease, peripheral vascular disease, serum albumin, and hematocrit levels [61,63-65].
The similarity in comorbid conditions and causes of hospitalization suggest that the comorbidity and complications observed in kidney failure manifest themselves well before the onset of kidney failure. Similar findings were observed in a study of patients with earlier stages of CKD referred to a nephrology service in Ontario, Canada [66].
The risk of cardiovascular mortality, and risk of kidney failure, disease progression, or acute kidney injury in patients with CKD progressively increases as GFR declines. In one study, GFR was estimated longitudinally from 1996 to 2000 in over 1 million enrollees of a United States integrated health care system [67]. The adjusted risk for cardiovascular events for patients with an estimated GFR (eGFR) of 45 to 59, 30 to 44, 15 to 29, and <15 mL/min/1.73 m2 was 1.4, 2.0, 2.8, and 3.4, respectively, and similar patterns were observed in the risk for hospitalization.
A detailed discussion of the association between CKD and morbidity from CVD is discussed separately. (See "Chronic kidney disease and coronary heart disease".)
Patients with CKD, particularly those with kidney failure, are at increased risk of mortality, particularly from CVD. In 2011 alone, more than 92,221 kidney failure patients died [57,68]. Survival probabilities for dialysis patients at one, two, and five years are approximately 81, 65, and 34 percent, respectively [56]. Rates for prevalent dialysis patients ≥65 years of age are nearly seven times higher than those in the general population [57]. The Global Burden of Disease (GBD) study 2015 reported that, among 315 diseases, the rank of CKD in terms of disability-adjusted life years rose from 30 in 1990 to 22 in 2005 and 20 in 2015 [69]. This is discussed in detail separately. (See "Chronic kidney disease and coronary heart disease" and "Moderately increased albuminuria (microalbuminuria) and cardiovascular disease" and "Patient survival and maintenance dialysis".)
In contrast to the GBD study results, in 2020, a retrospective cohort of 548,609 participants from the Alberta Kidney Disease Network with longitudinal information on severe CKD (GFR <30 mL/min) or kidney failure with or without clinical comorbidities (eg, coronary vascular disease, congestive heart failure, diabetes, cancer, among others), documented significant reductions in mortality and mean hospital stay between 2004 and 2015. These reductions compared favorably to other noncommunicable diseases except for mortality at five years for kidney failure cases under KRT, which failed to improve [70].
Likewise, another study examined excess mortality over and above the risk in the general population among patients on KRT in the United States between 1995 and 2013. Adjusted relative excess risk per five-year increment in calendar time ranged from 0.73 (0.69 to 0.77) for 0 to 14-year-olds to 0.88 (0.88 to 0.88) for ≥65-year-olds, which means that the excess risk of kidney failure-related death decreased by 12 to 27 percent over any five-year interval. Although these reductions correlated with time on dialysis and time with a functioning kidney transplant, the youngest persons with a functioning kidney transplant had the largest relative improvements [71].
The apparent discrepancy between the GBD study results and the above two studies can be explained by methodologic differences, including patients with all CKD stages entered in the GBD study. In addition, the increases in the burden of CKD reported in the GBD study are driven by population aging and increases in population size, which do not contradict the better age-adjusted outcomes at the individual level that were reported in the other two studies.
SUMMARY
●Global burden of CKD – The global prevalence of chronic kidney disease (CKD) is high, ranging from approximately 9 to 13 percent in different studies, and is about 1.3 times more frequent in females than in males. Between 1990 and 2017, the all-age CKD prevalence increased by approximately 29 percent. (See 'Global burden of CKD' above.)
Globally, the mortality rate from CKD increased by 42 percent between 1990 to 2017, driven by population aging and population growth. In parallel, CKD became the 12th leading cause of death in 2017 (it was the 17th leading cause in 1990). However, at the individual level, mortality and mean hospital stay has declined among people with CKD.
In addition to a shortened life expectancy, CKD is also strongly associated with disability.
●Regional differences in CKD burden – There are striking regional differences in CKD burden. This regional variation may reflect actual regional differences or partially relate to issues with glomerular filtration rate (GFR) estimation (eg, type of equation used), cut-off thresholds (especially among older adults), or one-off testing assessments. (See 'Regional disparities in CKD burden' above.)
●Burden of kidney failure – Approximately 0.1 percent of the world population has kidney failure (ie, end-stage kidney disease), and this proportion will increase over time. Despite significant growth in access to kidney replacement therapy (KRT; ie, dialysis or kidney transplantation), over 90 percent of patients with kidney failure in low- and low-middle income countries remain untreated (particularly in Asia and Africa). (See 'Kidney failure' above.)
Worldwide, hemodialysis is the most frequent treatment modality for kidney failure, mainly in high-income countries where the proportions of hemodialysis versus peritoneal dialysis are 80 to 90 percent versus 10 to 20 percent.
●Racial differences in kidney failure – Compared with White Americans, Black Americans have a 3.7-fold higher prevalence of kidney failure, likely a result of social determinants of health. In addition, specific apolipoprotein L1 (APOL1) polymorphisms confer a substantially higher risk of kidney failure in Black individuals. (See 'Incidence of kidney failure' above and 'Apolipoprotein L1 in African Americans' above.)
●Impact of CKD – Both early stages of CKD and kidney failure are associated with high morbidity and increased health care utilization. The risk of hospitalization and cardiovascular events in patients with CKD progressively increases as GFR declines (see 'Impact of CKD and kidney failure on morbidity and mortality' above). However, recent analyses on secular trends of advanced CKD and CKD on KRT suggest significant reductions in mortality and mean hospital stay over the past decades.
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Brian JG Pereira, MD, who contributed to earlier versions of this topic review.
