ZIDOVUDINE IS BENEFICIAL IN HUMAN-IMMUNODEFICIENCY-VIRUS ASSOCIATED NEPHROPATHY

Human immunodeficiency virus associated nephropathy (Hivan) is a distinct renal disease described in patients infected with the human immunodeficiency virus (HIV). Hivan is characterized by a nephrotic syndrome, enlarged kidneys, a histologic finding of focal and segmental glomerulosclerosis, and a very rapid progression to end-stage renal disease (ESRD). No therapeutic intervention has been shown, in a prospective evaluation, to either alter the course of established Hivan or to influence the emergence of Hivan in HIV-infected patients. We conducted a prospective study on 23 consecutively selected patients seen between 1989 and 1992 who were infected with the HIV, 14 (61%) of whom had significant proteinuria (greater than or equal to 2+). Percutaneous kidney biopsy was performed in 5 (36%) of the 14 subjects who had Significant proteinuria, and histologic examination of the kidney tissue revealed focal and segmental glomerulosclerosis in all 5 cases. Of the 14 subjects with proteinuria, 8 (57%) also had azotemia (serum creatinine level greater than or equal to 1.3 mg/dl). Nine (39%) of 23 subjects admitted intravenous drug use, while 9 (39%) of 23 subjects have had an opportunistic infection before enrollment in the study. The known duration of HIV infection before initiation of zidovudine therapy was 10.3 +/- (SD) 8 months. The mean CD4 count before zidovudine therapy was 195.9 +/- 117 (range 21-654) cells/mm(3). The mean dose of zidovudine administered was 543 +/- 117 (range 400-800) mg daily for a period of 20.4 +/- 11 (range 6-38) months. The clinical course of renal disease in the study subjects was compared to that of a control cohort of 28 HIV-infected patients with the nephrotic syndrome, presenting in ESRD for initiation of renal replacement therapy during the study period, who had never been treated with zidovudine or any other antiretroviral drug. Of 28 control patients, 14(50%) admitted intravenous drug use; the known duration of HIV infection before onset of ESRD was 14.6 +/- 8.6 months. These 28 control patients had been seen at an outpatient facility between 1989 and 1992 for anasarca and proteinuria without azotemia. The mean serum creatinine concentration of the 23 study subjects before zidovudine therapy was 1.2 +/- 0.4 (range 0.8-2.1) mg/dl. By contrast, 8 (35%) of 23 subjects who stopped zidovudine due to noncompliance progressed to ESRD within a mean of 8 +/- 2 (range 4-12) weeks, and each was begun on renal replacement therapy. Of these 8 patients, 2 died 10 and 12 weeks: respectively, after initiation of maintenance hemodialysis. These 8 patients had been on zidovudine therapy for a mean of 9 +/- 3 months before discontinuing the drug. Reinstituted zidovudine therapy had no obvious effect on their renal function. None of the 15 zidovudine-compliant subjects developed ESRD or worsening azotemia. The mean se:rum creatinine concentration at the end of the study period was 0.93 +/- 0.2 mg/dl. All patients initially free of proteinuria remained so. In the control patients, the interval from presentation with anasarca and proteinuria to onset of ESRD was 5.9 +/- 2.3 months. None of the control group were on any medication known to cause renal failure. Fourteen (50%) of 28 control patients died within 10 months after initiation of hemodialysis at a mean time of 3.8 +/- 2.1 months. We conclude that zidovudine is beneficial in HIV-associated nephropathy, and that discontinuing zidovudine treatment in HIV-infected patients with nephropathy may result in irreversible and accelerated loss of renal function.