Joseph V. Nally, Jr., MD Former Director, Center for Chronic Kidney Disease; Clinical Professor of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University
Address: Joseph V. Nally, Jr., MD, Glickman Urological and Kidney Institute, Q7, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; nallyj@ccf.org
Medical Grand Rounds articles are based on edited transcripts from Medicine Grand Rounds presentations at Cleveland Clinic. They are approved by the authors but are not peer-reviewed.
ABSTRACT
Recent decades have seen great advances in the understanding of chronic kidney disease, spurred by standardizing disease definitions and large-scale patient surveillance. African Americans are disproportionately affected by the disease, and recently discovered genetic variants in APOL1 that protect against sleeping sickness in Africa provide an important explanation for the increased burden. Studies are now under way to determine if genetic testing of African American transplant donors and recipients is advisable.
KEY POINTS
Patients with chronic kidney disease are more likely to die than to progress to end-stage disease, and cardiovascular disease and cancer are the leading causes of death.
As kidney function declines, the chance of dying from cardiovascular disease increases.
African Americans tend to develop kidney disease at a younger age than whites and are much more likely to progress to dialysis.
About 15% of African Americans are homozygous for a variant of the APOL1 gene. They are more likely to develop kidney disease and to have worse outcomes.
Heart disease risk increases with declining kidney function
Navaneethan et al9 examined the leading causes of death between 2005 and 2009 in patients with chronic kidney disease in the Cleveland Clinic database, which included more than 33,000 whites and 5,000 African Americans. During a median follow-up of 2.3 years, 17% of patients died, with the 2 major causes being cardiovascular disease (35%) and cancer (32%) (Table 1). Interestingly, patients with fairly well-preserved kidney function (stage 3A) were more likely to die of cancer than heart disease. As kidney function declined, whether measured by estimated GFR or urine albumin-to-creatinine ratio, the chance of dying of cardiovascular disease increased.
Similar observations were made by Thompson et al10 based on the Alberta Kidney Disease Network database. They tracked cardiovascular causes of death and found that regardless of estimated GFR, cardiovascular deaths were most often attributed to ischemic heart disease (about 55%). Other trends were also apparent: as the GFR fell, the incidence of stroke decreased, and heart failure and valvular heart disease increased.
AFRICAN AMERICANS WITH KIDNEY DISEASE: A DISTINCT GROUP
African Americans constitute about 12% of the US population but account for:
31% of end-stage renal disease
34% of the kidney transplant waiting list
28% of kidney transplants in 2015 (12% of living donor transplants, 35% of deceased donor transplants).
In addition, African Americans with chronic kidney disease tend to be:
Younger and have more advanced kidney disease than whites11
Much more likely than whites to have diabetes, and somewhat more likely to have hypertension
Adapted from Navaneethan SD, Schold JD, Arrigain S, Jolly SE, Nally JV Jr. Cause-specific deaths in non-dialysis-dependent CKD. J Am Soc Nephrol 2015; 26:2512–2520.
Figure 2. Risk for all-cause and major cause-specific death in black vs white patients.
More likely than whites to die of cardiovascular disease (37.4% vs 34.2%) (Figure 2).9
Overall, the prevalence of chronic kidney disease is slightly higher in African Americans than in whites. Interestingly, African Americans are slightly less likely than whites to have low estimated GFR values (6.2% vs 7.6% incidence of < 60 mL/min/1.73 m2) but are about 50% more likely to have proteinuria (12.3% vs 8.4% incidence of urine albumin-to-creatinine ratio ≥ 30 mg/g).
More likely to be on dialysis, but less likely to die
Although African Americans have only a slightly higher prevalence of chronic kidney disease (about 15% increased prevalence) than whites,12 they are 3 times more likely to be on dialysis.
Nevertheless, for unknown reasons, African American adults on dialysis have about a 26% lower all-cause mortality rate than whites.5 One proposed explanation for this survival advantage has been that the mortality rate in African Americans with chronic kidney disease before entering dialysis is higher than in whites, leading to a “healthier population” on dialysis.13 However, this theory is based on a small study from more than a decade ago and has not been borne out by subsequent investigation.
African Americans with chronic kidney disease: Death rates not increased
African Americans over age 65 with chronic kidney disease have all-cause mortality rates similar to those of whites: about 11% annually. Breaking it down by disease severity, death rates in stage 3 disease are about 10% and jump to more than 15% in higher stages in both African Americans and whites.5
However, African Americans with chronic kidney disease have more heart disease and much more end-stage renal disease than whites.
Disease advances faster despite care
The incidence of end-stage renal disease is consistently more than 3 times higher in African Americans than in whites in the United States.5,14
Multiple investigations have tried to determine why African Americans are disproportionately affected by progression of chronic kidney disease to end-stage renal disease. We recently examined this question in our Cleveland Clinic registry data. Even after adjusting for 17 variables (including demographics, comorbidities, insurance, medications, smoking, and chronic kidney disease stage), African Americans with chronic kidney disease were found to have an increased risk of progressing to end-stage renal disease compared with whites (subhazard ratio 1.38, 95% confidence interval 1.19–1.60).
We examined care measures from the Cleveland Clinic database. In terms of the number of laboratory tests ordered, clinic visits, and nephrology referrals, African Americans had at least as much care as whites, if not more. Similarly, African Americans’ access to renoprotective medicines (angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, statins, beta-blockers) was the same as or more than for whites.
Although the frequently attributed reasons surrounding compliance and socioeconomic issues are worthy of examination, they do not appear to completely explain the differences in incidence and outcomes. This dichotomy of a marginally increased prevalence of chronic kidney disease in African Americans with mortality rates similar to those of whites, yet with a 3 times higher incidence of end-stage renal disease in African Americans, suggests a faster progression of the disease in African Americans, which may be genetically based.
Adapted from Navaneethan SD, Schold JD, Arrigain S, Jolly SE, Nally JV Jr. Cause-specific deaths in non-dialysis-dependent CKD. J Am Soc Nephrol 2015; 26:2512–2520.
