Abstract
There are evolving epidemiological and biological data to support an association between the gene encoding apolipoprotein-L1 (APOL1) and progressive chronic kidney disease (CKD) among African-Americans. Individuals with two APOL1 risk alleles are at greater risk of incident albuminuria, CKD, and progression to end-stage renal disease despite optimal blood pressure management and use of angiotensin-converting enzyme inhibitors. These variants also appear to influence outcomes in donor and recipients in kidney transplantation. Recent studies have also variably shown a potential role of APOL1 variants in cardiovascular disease. A number of studies have addressed genetic and environmental factors such as HIV but most do not modify the course of APOL1-related kidney disease. Although the exact mechanism remains unclear, functional studies have demonstrated the effect of APOL1 and related protein on innate immunity and cytotoxicity. APOL1 is an important genetic risk factor for kidney disease among African-Americans. With approximately one in 10 African-Americans at risk, further studies are warranted to identify underlying biological mechanisms and other potential modifiers leading to CKD. Moreover, studies that clarify the association of APOL1 variants with cardiovascular disease, independent of CKD, are also needed.
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