Successful antiretroviral therapy for human immunodeficiency virus (HIV) infection has altered the spectrum of HIV-associated kidney disease over the past 30 years, according to the authors of a new review published in the New England Journal of Medicine.

“During this period, evidence of nephrotoxic effects of antiretroviral therapy and the prevalence of kidney diseases resulting from aberrant metabolism and aging have increased,” Scott D. Cohen, MD, MPH, Jeffrey B. Kopp, MD, and Paul L. Kimmel, MD explained. “HIV-associated nephropathy, although much less frequent now than 20 years ago, is currently understood to arise from complex interactions among the virus (renal-cell infection and the effect of viral proteins), host genotype, host response (interferon production), and perhaps most importantly, effective treatment.”

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Approximately 1.2 million individuals in the United States are infected with HIV, and the incidence has remained stable at about 50,000 infections per year over the past decade, Dr Cohen and his coauthors noted.

Patients infected with HIV are at increased risk for both acute kidney injury (AKI) and chronic kidney disease (CKD) due to nephrotoxic medications, infection, and immune responses to infection, the authors stated. Typical manifestations of AKI include acute tubular necrosis and acute interstitial nephritis. The differential diagnosis of AKI requires microscopic examination of urine and evaluation of urinary osmolality and sodium and creatinine concentration.

Current antiretroviral therapies suppress viral replication, but they may result in chronic inflammation, premature aging, and metabolic disorders such as hyperlipidemia and diabetes—conditions associated with CKD.

HIV-associated nephropathy, HIV immune-complex kidney disease, kidney disease of thrombotic microangiopathy, and nephrotoxicity can result from either AKI or CKD, the authors noted.

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Dr Cohen and his colleagues said determining the cause of incipient and progressive renal disease in HIV-infected patients on antiretroviral therapy may be difficult. “Clues can be found in the amount and character of urine protein excretion and in the urine sediment,” they wrote. “A renal biopsy may be necessary to determine diagnosis, prognosis, and management.”

The authors cited an observational study (AIDS 2012;26:1907-915) demonstrating that antiretroviral therapy is associated with slower progression of CKD. Some antiretroviral medications, however, including tenofovir disoproxil fumarate and ritonavir-boosted protease inhibitors, are associated with an increased risk of CKD progression.

Although the incidence of HIV-associated end-stage renal disease has leveled off, the prevalence of HIV-infected patients on dialysis in the United States continues to rise, the authors noted. They cited a study (Nephrol Dial Transplant 2015;30:1734-1740) showing that survival among HIV-infected patients on dialysis is similar to that of dialysis not infected with HIV.

“Additional research, including well-designed randomized, controlled trials, is needed to determine effective therapeutic approaches to treating the diverse renal manifestations of HIV infection and improve the outcomes of treatment,” Dr Cohen and co-authors wrote.


Cohen SD, Kopp JB, and Kimmel PL. Kidney diseases associated with human immunodeficiency virus infection. New Engl J Med.