ATLANTA – Variants in the gene encoding apolipoprotein L1 are associated with a nearly twofold increased risk of chronic kidney disease progression in African American patients, according to an analysis of data from the Chronic Renal Insufficiency Cohort and the African American Study of Kidney Disease and Hypertension.
In addition, kidney function is lost at double the rate in patients with the apolipoprotein L1 (APOL1) renal risk variants.
The findings – which persisted regardless of chronic kidney disease (CKD) etiology and well-controlled blood pressure – may explain, in part, the markedly increased risk of end-stage renal disease (ESRD) in African American patients, compared with European American patients, Dr. Afshin Parsa of the University of Maryland, Baltimore, reported at Kidney Week 2013.
The findings were published simultaneously online Nov. 9 in the New England Journal of Medicine (2013 Nov. 9 [doi:10.1056/NEJMoa1310345]), and will appear in the Dec. 5 print issue.
In the CRIC (Chronic Renal Insufficiency Cohort) study, 2,955 patients with CKD, nearly half of whom (46%) had diabetes, were evaluated based on whether they had zero or one copy of the APOL1 variants (low-risk group) or two copies of the variants (high-risk group). The primary outcomes in that cohort were the slope in the estimated glomerular filtration rate (eGFR), and the composite of ESRD, or a reduction of 50% in the eGFR from baseline, said Dr. Parsa, who was one of the CRIC investigators.
Among black patients in the high-risk group, the decline in eGFR was significantly more rapid and the rate of the composite renal outcome significantly higher than in white patients in that group, regardless of diabetes status. The rate of decline was similar among black and white patients in the low-risk group.
Among African American patients with diabetes in the low-risk group, white patients with diabetes, and African American patients with diabetes in the high-risk group, the eGFR slopes were –2.7, –1.5, and –4.3 mL/min per 1.73 m2 per year, respectively. Among those without diabetes, the corresponding slopes were –0.7, –1.0, and –2.9.
The adjusted hazard ratios for a renal event were 1.95 and 1.40 for African American patients, compared with white patients in the high-risk and low-risk groups with diabetes, respectively. The corresponding hazard ratios among those without diabetes were 2.68 and 1.57. The adjusted hazard ratio for the composite renal outcome was 1.61 for African American patients in the high-risk vs. the low-risk groups.
In the AASK (African American Study of Kidney Disease and Hypertension) study, 693 African American patients with hypertension-related chronic kidney disease and without diabetes were evaluated, and the primary outcome measure was a composite of end-stage renal disease or a doubling of the serum creatinine level.
The primary outcome occurred in 58.1% of those in the high risk group, compared with 36.6% of those in the low-risk group (hazard ratio, 1.88). No interactions between APOL1 status and trial interventions or the presence of baseline proteinuria were seen in AASK, Dr. Parsa said during a press briefing at the conference, which was sponsored by the American Society of Nephrology.
Also, the effect of APOL1 on CKD progression was not confounded by blood pressure levels, he noted.
The findings of the current analysis build on those from landmark 2008 research that led to identification of the APOL1 gene variants as a risk factor for kidney disease not associated with diabetes, he said, adding that the current findings are the first to provide direct evidence that the APOL1 high-risk variants are associated with increased disease progression over time.
This could potentially lead to genotyping of African Americans to assess their risk for disease progression, and could also lead to new treatment strategies for slowing the progression of CKD, the investigators said, noting that such strategies are currently limited.
The findings do not, however, fully explain the well-documented racial disparities in ESRD. In the United States, African Americans patients have about twice the risk of ESRD as do white patients, even after accounting for differences in socioeconomic and clinical risk factors.
The study results highlight the need to identify other risk factors that can account for residual disparities in end-stage renal disease between African American and white patients, they concluded.
This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Parsa reported having no disclosures.