November 3, 2011

Gene Variant Increases Risk of Kidney Disease in HIV-Positive African Americans

African Americans living with HIV who don’t receive antiretroviral therapy and have inherited an altered form of a gene, called APOL1, from both parents have about a 50 percent lifetime risk of developing kidney disease, according to a new paper published by National Institutes of Health (NIH) researchers in the Journal of the American Society of Nephrology. The finding brings scientists closer to understanding why African Americans, regardless of whether or not they’re living with HIV, are significantly more likely to develop kidney failure than whites.

NIH researchers have begun tracing the effects of having two variants of the APOL1 gene, which occurs in about 12 percent of African Americans.

Researchers earlier linked this gene to susceptibility for kidney disease. When a person has kidney disease, the kidneys are unable to fully remove waste products and extra water from the blood. The researchers studied a common kidney disease called focal segmental glomerulosclerosis (FSGS), which often progresses to end-stage kidney disease and the need for dialysis or a kidney transplant. The researchers studied FSGS patients who came to the NIH Clinical Center in Bethesda, Maryland, or other collaborating medical centers, and who provided blood samples for genetic studies.

“These findings explain nearly all of the excess risk of non-diabetic kidney failure in African Americans,” said the National Cancer Institute’s Cheryl Winkler, PhD, in an accompanying announcement. “African Americans with no variant or one variant have about the same risk of end-stage kidney disease as their white counterparts. People with two APOL1 variants have greatly increased risk of particular kidney diseases—by 17- to 30-fold.”

The researchers found that African Americans with two copies of the APOL1 variants have about a 4 percent lifetime risk of developing FSGS. Those who develop kidney disease tend to do so at younger ages than other FSGS patients, with 70 percent diagnosed with FSGS between age 15 and 39, compared to 42 percent in that age group for people with one or no APOL1 variants.

Possessing two APOL1 variants also raises the risk for African Americans with HIV of developing HIV-associated nephropathy (HIVAN)—a type of kidney disease that develops in some people living with the virus—to 50 percent among those not receiving antiretroviral (ARV) treatment, the authors suggest. ARV treatment, they add, appears fairly effective at preventing HIVAN.

“The much higher risk of kidney disease in patients with HIV suggests that a second hit with a virus or other unknown factor is necessary for kidney injury in people who have two APOL1 variants,” Winkler said. This may be why most people with two APOL1 variants do not develop kidney disease.

People living with FSGS with two APOL1 variants respond as well to steroid treatments as their FSGS-affected peers who don’t have the variants, making steroids a viable treatment option, the researchers found. Further, they found that kidney disease progresses more rapidly in patients with two APOL1 variants, and they hypothesize that aggressive therapy may be advisable.

“In the future, knowing that you have these gene variants and are at increased risk of developing kidney disease may tell you when to start screening for the disease and how to choose therapy,” said NIH kidney specialist Jeffrey Kopp, MD, in the announcement. “However, more research is needed, including clinical trials that test whether early genetic testing in the African-American population makes a difference, whether screening tests for young adults with the variant copies detects kidney disease at an early stage, and whether early treatment affects long-term outcome.”

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Michael, Northeast Corridor, 2011-11-08 09:46:06
I stated I was a victim of it over 7 years ago and received a kidney transplant in late May of this year that worked when a prior transplant 14 months ago failed. I am HIV+ and have been for over 25 years. Found out in 1983. Received transplant at Beth Israel Deaconess Medical Center in Boston. They transplant HIV / AIDS patients. Contact #617-632-9700 (The Transplant Center).

Michael, Northeast Corridor, 2011-11-08 09:41:47
I knew about this over 7 years ago because I was a victim of it.