HIV-associated nephropathy (HIVAN), a common presentation among patients with advanced HIV disease during the early AIDS epidemic in the 1980s, is rarely encountered by nephrologists now that HIV infection is controlled more effectively by antiretroviral drugs.

But kidney disease rates remain higher among HIV-positive individuals, particularly those of African and Hispanic descent, and HIV infection continues to present clinical challenges that can lead to chronic kidney disease (CKD) and end-stage renal disease.

Christina Wyatt, MD, MSc, a Duke nephrologist, researcher, and specialist in treating kidney disease in HIV-positive adults, encourages nephrologists to be aware of the changing spectrum of kidney disease in in the current era of effective HIV treatment and prevention. While HIVAN is rarely seen now—usually only among patients who are not on antiretroviral therapy either because of a new diagnosis or nonadherence—Wyatt focuses on related conditions that may increase the risk of CKD among HIV-positive individuals, including:

• Non-collapsing focal segmental glomerulosclerosis
• Immune complex disease (with or without hepatitis)
• Diabetic nephropathy
• Arterionephrosclerosis
• Drug toxicity associated with antiretrovirals

“While we still see an occasional, newly diagnosed HIVAN presentation, what we encounter more often are the same conditions nephrologists see in general practice,” Wyatt says. But she cautions that the causal link between HIV and kidney diseases other than HIVAN remains less clear. “These patients often have other risk factors such as diabetes, hypertension, hepatitis co-infection, or antiretroviral toxicity that may be contributing to the kidney disease."

Nephrologists working with HIV-positive patients also see more immune complex kidney diseases, Wyatt says. Examples are lupus-like glomerulonephritis, membranous nephropathy, and IgA nephropathy. “At this point, these conditions are not as well studied, partly because the terminology in the studies has not been clarified,” Wyatt says. “But we are certainly seeing them.”

With effective antiretroviral therapy, the lifespans of adherent patients now extend into old age. Kidney disease, however, remains a significant concern. “Patients with HIV appear to have a faster progression of kidney disease,” Wyatt says. “This is particularly true for those patients who also have diabetes.”

The impact of antiretroviral use remains a significant concern in this patient population. “We know that some of the antiretroviral drugs are nephrotoxic,” Wyatt says, citing data that suggest that some protease inhibitors and the older prodrug of tenofovir, tenofovir disoproxil fumarate, appear to present higher risks.

“When treating an HIV-positive individual with kidney disease, we should balance all the traditional risk factors such as diabetes and hypertension, but it’s also critical to review the medication list with a close look at the antiretrovirals,” Wyatt says. In some cases, this may require attention to the individual components in fixed dose combination pills, which are frequently used to improve adherence and reduce pill burden.

Nephrologists should also be aware the several antiretroviral agents can interfere with the tubular secretion of creatinine, causing a decline in creatinine-based estimates of glomerular filtration rate that may not reflect a true decrease in kidney function.