Captopril prevents nephropathy in HIV-transgenic mice

Abstract

Transgenic mice (T26) bearing the envelope, regulatory, and accessory genes of HIV- I develop renal disease resembling human HIV-associated nephropathy (HIVAN). Effects of vehicle (VEH) and the angiotensin-converting enzyme inhibitor captopril (CAP) were examined in wild-type (WT) or T26 mice treated from 7 to 100 d of age. Mortality was lower in CAP T26 mice (30 mg/kg: 8%; 100 mg/kg: 12%) than VEH T26 mice (52%). The urinary protein/creatinine ratio was increased in VEH T26 mice (19.5+/-7.60) versus WT mice (6.1+/-0.83), but not in low-dose (7.3+/-0.94) or high-dose (8.2+/-1.02) CAP T26 mice. Blood urea nitrogen was higher in VEH T26 mice (52+/-16.2 mg/dl) than VEH WT mice (24+/-0.8). Blood urea nitrogen was also elevated in CAP WT (high dose: 43+/-2.1 mg/dl) and T26 mice (high dose: 42+/-2.4 mg/dl). Glomerular injury was higher in VEH T26 mice (6.8+/-0.58) than VEH WT mice (0.2+/-0.08) or CAP T26 mice (low dose: 1.1+/-0.17; high dose: 0.7+/-0.13). Tubulointerstitial injury was also greater in VEH T26 mice (1.1+/-0.10) than VEH WT mice (0.2+/-0.08) or CAP T26 mice (low dose: 0.4+/-0.10; high dose: 0.3+/-0.10). These data validate recent nonrandomized studies of captopril in HIV-infected patients, and suggest that an angiotensin-converting enzyme substrate is an important mediator in HIVAN. A randomized placebo-controlled trial of captopril in HIVAN may be warranted.