Can APOL1 Explain Higher Risk of ESRD in Black Patients?

Increased rates of kidney disease progression among black patients—regardless of cause—are at least partly related to variants of the apolipoprotein L1 gene (APOL1), suggests a study in the New England Journal of Medicine.

The researchers analyzed data from 693 black patients from the African American Study of Kidney Disease and Hypertension (AASK) who had chronic kidney disease (CKD) attributed to hypertension, and 2955 white or black patients with CKD from the Chronic Renal Insufficiency Cohort (CRIC) study, about half of whom had diabetes. Both analyses compared outcomes in a “high-risk” group with two copies of high-risk APOL1 variants versus a “low-risk” group with zero or one copy.

In the AASK data, black participants with high-risk APOL1 status were more likely to meet a composite outcome of ESRD or doubling of serum creatinine: 58.1 percent versus 36.6 percent, hazard ratio 1.88. The association was unaffected by study interventions or baseline proteinuria.

Among CRIC participants, those with two copies of APOL1 risk variants had a steeper decline in estimated GFR. The high-risk APOL1 group also had a higher rate of a composite outcome of ESRD or a 50 percent reduction in estimated GFR. Among black CRIC participants, the risk of the composite outcome was 46 percent higher in the high-risk APOL1 group than in the low-risk group. This was so regardless of the presence or absence of diabetes.

Previous research has linked APOL1variants to increased rates of kidney diseases in black individuals, including ESRD in patients without diabetes. On the basis of the new study, high-risk APOL1 genes appear to contribute to an elevated risk of ESRD and progressive CKD in black versus white patients, regardless of diabetes status. The researchers write that their study provides “direct evidence…that the APOL1 high-risk variants are associated with increased disease progression over the long term” [Parsa A, et al. APOL1 risk variants, race, and progression of chronic kidney disease. N Engl J Med 2013; 369:2183–2196].