Renal failure reversed in first documented case

HAART therapy most effective in early stages

About 10% of patients with HIV infection develop kidney failure. But for the first time, doctors have reversed kidney disease in an HIV-infected patient by putting the patient on highly active antiretroviral therapy (HAART).

The case, which took place at the University of Maryland Medical Center, provides the first evidence of a connection between antiretroviral therapy and a dramatic improvement in kidney function in an AIDS patient who had started dialysis.1 It also suggests that the therapy may eliminate the need for long-term dialysis in HIV patients, although researchers say more study is needed.

"It has been a feeling among doctors who treat HIV patients that current antiretroviral therapy may help prevent kidney failure, but it had never been documented," says Emilio Ramos, MD, a nephrologist at the University of Maryland Medical Center.

The patient, a 37-year-old African-American man with schizophrenia and bipolar disorder, was admitted with psychotic symptoms after stopping his psychotherapeutic medications. A battery of tests showed that he was HIV-positive with moderate renal disease.

A week before dialysis was initiated, a percutaneous biopsy was done, showing changes typical of HIV-1-associated nephropathy. Doctors immediately started triple antiretroviral therapy (stavudine 20mg/day, lamivudine 50mg/day, and nelfinavir 1,250 mg twice a day). After 13 weeks of treatment and 12 weeks of hemodialysis three times a day, a 24-hour urine collection contained 0.7 g protein and 10.6 mmol creatinine. Two weeks later, 24-hour urine tests were similar, and dialysis was discontinued. A repeat percutaneous renal biopsy also was performed, showing recovery of renal functions.

This case supports the hypothesis that viral proteins and/or the host of cytokines released during active viral replication can have cytopathic effects on the kidneys, say researchers. However, it is also possible that nephropathy may occur as a result of direct infection of the glomerular and tubular epithelial cells by HIV-1 in susceptible patients, because HIV-1 has been shown to be in the kidneys of seropositive individuals both with and without nephropathy, researchers added.

Ramos says antiretroviral therapy is most effective in the early stages of kidney failure, but will not reverse kidney failure in patients who have been on dialysis for a long time and whose kidneys have deteriorated.

"Whenever there are more than two grams of protein in the urine and creatine that is 1.6 or 1.8, the patient should have a kidney biopsy," he says. "If the biopsy shows a lesion consistent with HIV nephropathy, physicians should try the antiretroviral therapy to see if there is improvement in proteinuria or renal function."

Other reports have indicated some transient improvement in renal function and proteinuria in patients with nephropathy after treatment with steroids, angiotensin-converting enzyme blockers, or zidovudine, though most of these patients ultimately required long-term dialysis, say researchers.

"Whether early initiation of antiretroviral therapy, before substantial fibrosis occurs, results in optimum benefit is unknown," says Ramos. "The response of our patient to triple antiretroviral therapy suggests that studies may be warranted to determine whether such therapy may obviate the need for long-term dialysis in some patients." He has begun a preliminary study and hopes to enroll 15 patients.

"This case is encouraging because it implies that even a late-stage complication of HIV like kidney failure can be reversed with these powerful drugs," says Lori Fantry, MD, an AIDS specialist at the University of Maryland Medical Center and assistant professor of medicine at the University of Maryland School of Medicine in Baltimore.

Reference

1. Wali R, Drachenberg C, Papadimitriou J. HIV-1-associated nephropathy and response to highly active antiretroviral therapy. Lancet 1998; 352:783-784.