Zidovudine Is Beneficial in Human Immunodeficiency Virus Associated Nephropathy

Abstract

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 ( > 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 > 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/mm³. 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 serum 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 ES...

Recent Progress in HIV-Associated Nephropathy

“…Ifudu et al (67) studied 23 HIV-1-seropositive patients, 14 of whom had at least 2ϩ proteinuria. HIVAN was diagnosed in the five patients who underwent renal biopsy.…”

“…Patients with HIVAN who are not treated with antiretrovirals, ACE inhibitors, or prednisone, generally have a poor renal prognosis with a mean time to progression to ESRD of 1 to 3 mo (13,67,72). The renal prognosis in the HAART era is less well defined.…”

HIV-Associated Nephropathy

“…Early uncontrolled and largely retrospective studies suggested a beneficial effect of this agent, primarily if treatment was initiated when serum creatinine was normal or slightly elevated. In a prospective study using historical controls, Ifudu et al [24]reported on 23 patients, only 14 of whom had either proteinuria or renal insufficiency, who were treated with AZT for a mean of 20 months. Eight noncompliant patients progressed to ESRD.…”

“…Of the 15 compliant patients, none progressed to ESRD, and none who were initially without proteinuria developed that condition. Half of the 28 historical controls with nephrotic syndrome and ESRD who were never treated with AZT died within 10 months of initiation of hemodialysis [24]. Positive as this study is, it suffers from a lack of tissue diagnosis for most patients; only 5 had a kidney biopsy, but all 5 had HIVAN.…”

Steady-State Pharmacokinetics of Lamivudine in Human Immunodeficiency Virus-Infected Patients with End-Stage Renal Disease Receiving Chronic Dialysis

“…This is due in part to the development of an HIV-associated nephropathy (HIVAN), characterized by massive proteinuria and rapidly progressive renal failure, in a subset of patients infected with HIV (8,13,24). Although combination antiretroviral therapy appears to slow the progression of HIVAN to end-stage renal disease (ESRD) in many cases (9,16,27), the total number of persons with ESRD due to HIVAN is expected to increase due to the increasing prevalence of HIV-1 infection (E. J. Schwartz, L. Szczech, J. A. Winston, and P. E. Klotman, J.…”