Target Organ Damage in African American Hypertension: Role of APOL1
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Apolipoprotein L1 (APOL1) gene association studies and results of the African American Study of Kidney Disease and Hypertension are disproving the longstanding concept that mild to moderate essential hypertension contributes substantially to end-stage renal disease susceptibility in African Americans. APOL1 coding variants underlie a spectrum of kidney diseases, including that attributed to hypertension (labeled arteriolar or hypertensive nephrosclerosis), focal segmental glomerulosclerosis, and HIV-associated nephropathy. APOL1 nephropathy risk variants persist because of protection afforded from the parasite that causes African sleeping sickness. This breakthrough will lead to novel treatments for hypertensive African Americans with low-level proteinuria, for whom effective therapies are lacking. Furthermore, APOL1 nephropathy risk variants contribute to racially variable allograft survival rates after kidney transplantation and assist in detecting nondiabetic forms of nephropathy in African Americans with diabetes. Discovery of APOL1-associated nephropathy was a major success of the genetics revolution, demonstrating that secondary hypertension is typically present in nondiabetic African Americans with nephropathy.
KeywordsAfrican American African sleeping sickness Arteriolar nephrosclerosis APOL1 Chronic kidney disease Dialysis End-stage renal disease ESRD: Focal segmental glomerulosclerosis Genetics Glomerulosclerosis Hypertension Hypertensive nephrosclerosis Kidney disease Kidney donors MYH9 Nondiabetic nephropathy Racial differences Trypanosoma brucei rhodesiense Transplantation
This work was supported by NIH grants R01 HL56266, RO1 DK070941, and RO1 DK084149.
No potential conflicts of interest relevant to this article were reported.
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