CAPTOPRIL PREVENTS NEPHROPATHY IN HIV-TRANSGENIC MICE

Transgenic mice (T26) bearing the envelope, regulatory, and accessory genes of HIV-1 develop renal disease resembling human HIV-associated n ephropathy (HIVAN). Effects of vehicle (VEH) and the angiotensin-conve rting 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 C AP T26 mice (30 mg/kg: 8%, 100 mg/kg: 12%) than VEH T26 mice (52%). Th e 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 w as 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 no nrandomized studies of captopril in HIV-infected patients, and suggest that an angiotensin-converting enzyme substrate is an important media tor in HIVAN. A randomized placebo-controlled trial of captopril in HI VAN may be warranted.