Captopril and renal survival in patients with human immunodeficiency virus nephropathy

被引:113
作者
Kimmel, PL
Mishkin, GJ
Umana, WO
机构
[1] Div. of Ren. Dis. and Hypertension, Department of Medicine, George Washington Univ. Med. Center, Washington, DC
[2] Div. of Ren. Dis. and Hypertension, Department of Medicine, George Washington Univ. Med. Center, Washington, DC 20037
关键词
antiretroviral drug; captopril; human immunodeficiency virus; chronic kidney disease; focal glomerulosclerosis; proteinuria;
D O I
10.1016/S0272-6386(96)90302-9
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
The pathogenesis of human immunodeficiency virus-associated nephropathy (HIVAN) is unknown, but it is characterized by aggressive glomerulosclerosis, tubulopathy, and interstitial inflammation. Currently, no therapy has been proven effective for HIVAN. Angiotensin II has been implicated in the pathogenesis of progressive renal disease in the absence of HIV infection, and treatment with captopril enhances renal survival in patients with diabetic glomerulosclerosis. Serum angiotensin-converting enzyme levels are elevated in patients with HIV infection, We therefore compared the course of 18 patients with biopsy-proven HIVAN (nine treated three times per day with captopril and nine not treated [controls]). The controls were matched to the study patients by age, race, gender, and level of serum creatinine concentration. Renal survival was measured from time of biopsy and treatment with captopril until onset of therapy for end-stage renal disease. Differences between the groups' survival were assessed by Kaplan-Meier and Cox regression analyses. Seven African-American men and two women were in the captopril-treated group, and eight African-American men and one woman were in the control group. No control patient died before the initiation of dialysis. There was no difference between initial mean serum creatinine concentration (3.4 +/- 0.7 mg/dL v 3.7 +/- 0.5 mg/dL), CD4 count (66 +/- 27/mu L v 92 +/- 15/mu L), or age (41.4 +/- 4.1 years v 36.4 +/- 2.6 years) in the study patients and controls, respectively, but the mean urinary protein to creatinine ratio was higher in the study patients. Renal survival was enhanced in the patients compared with the controls (mean renal survival, 156 +/- 71 days v 37 +/- 5 days, respectively; curves different; P < 0.002, Mantel-Cox log-rank test). Captopril and antiretroviral therapy were associated with enhanced renal survival in a Cox regression analysis, while age, level of serum creatinine, urinary protein to creatinine ratio, and CD4 count were not. These data suggest that treatment with captopril and antiretroviral therapy might be useful in delaying the rapidly progressive renal failure characterizing HIVAN. Captopril might exert its effects by reducing angiotensin II levels, or, alternatively, through decreasing renal tissue expression of growth factors and cytokines or by affecting HIV protease activity and therefore extent of productive renal infection. Such findings must be confirmed by randomized, double-blind, placebo-controlled trials. (C) 1996 by the National Kidney Foundation, Inc.
引用
收藏
页码:202 / 208
页数:7
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