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Abstract

Clin. Pract. (2014) 11(2), 139–143 ISSN 2044-9038 part of Parsa A, Kao WH, Xie D et al.; AASK Study Investigators; CRIC Study Investigators. APOL1 risk variants, race and progression of chronic kidney disease. N. Engl. J. Med. 369(23), 2183–2196 (2013). For decades, it has been observed that African–Americans experience a more rapid progression of chronic kidney disease (CKD) in virtually every etiology of kidney disease. This has been ascribed to more severe hypertension, poor risk factor control and noncompliance. Heretofore, a search for genetic determinants among African–Americans has been unrevealing. High-density lipoprotein cholesterol particles contain major apolipoproteins A-I and A-II, and minor apolipoproteins, including A-IV, A-V, C-I, C-II, C-III, D, E, F, H, J, L, M, O and P. Polymorphisms of these apolipoproteins have been associated with changes in reverse cholesterol transport function, oxidation and now, most recently, altered catabolism. High-density lipoprotein is filtered in the glomerulus and then catabolized by the proximal tubular cells. A mutant form of apo-L has been described in African–Americans that may have a protective effect against trypanosomes. APOL1 polymorphisms have a prevalence of approximately 30 and 2% among African–Americans and Caucasians, respectively. In this paper, data from two clinical studies, one exclusively in nondiabetic African–Americans with hypertension (AASK) and the other in patients screened for CKD (CRIC), variants in the gene for APOL1 were assessed according to whether they had two high-risk APOL1 variants (APOL1 high-risk group) or 0 or 1 copy (APOL1 low-risk group) [1]. In both studies, among those with and without diabetes, there was a more rapid progression of CKD, including the need for dialysis, in African–Americans with two alleles containing mutant variants of the APOL1 gene. This and other studies suggest that APOL1 variants are associated with a 50–100% increased risk of rapid progression of CKD and may be related to a toxic or adverse process invoked by proximal tubular cell catabolism of this apoprotein. So, in summary, APOL1 genetic abnormalities appear to be a major genetic basis for the difference between rates of progression of CKD between African–Americans and Caucasians.