COMBINED ANTIHYPERTENSIVE AND LIPID-LOWERING THERAPY IN EXPERIMENTAL GLOMERULONEPHRITIS

We examined the interrelation between systemic hypertension, hyperlipi demia, and progressive renal injury in experimental glomerulonephritis . Induction of nephrotoxic serum nephritis in Sprague-Dawley rats led to systemic hypertension and hyperlipidemia. Four groups of rats were studied over a 16-week period: (1) untreated nephritic rats; (2) nephr itic rats treated with hydralazine, reserpine, and lasix (AH); (3) nep hritic rats treated with lovastatin (4 mg/kg) (Lova); and (4) nephriti c rats treated with combined antihypertensive/lipid-lowering therapy ( AH/Lova). Systolic blood pressure rose progressively in untreated rats (152+/-4 mm Hg at 16 weeks). Blood pressure was reduced by antihypert ensive therapy (P<.001) (108+/-2 mm Hg in the AH group and 111+/-3 mm Hg in the AH/Lova group) but remained elevated in animals treated with lovastatin alone (P>.05) (156+/-3 mm Hg in the Lova group). Serum cho lesterol rose progressively in untreated rats (3.70+/-0.85 mmol/L [143 +/-33 mg/dL] at 16 weeks). The rise in serum cholesterol was prevented by lovastatin therapy (P<.001) (2.22+/-0.41 mmol/L [86+/-16 mg/dL] in the Lova group and 2.09+/- 0.52 mmol/L [81+/-2 mg/dL] in the AH/Lova group) but not antihypertensive therapy (P>.05) (2.92+/-0.65 mmol/L [1 13+/-25 mg/dL] in the AK group). Proteinuria was reduced by antihypert ensive therapy (P<.001) and lipid-lowering therapy (P<.05) (16-week va lues: 1.069+/-0.167 g/d in untreated rats, 0.663+/-0.164 g/d in the Lo va group, 0.392+/-0.051 g/d in the AH group, and 0.176+/-0.035 g/d in the Ah/Lova group). Glomerular injury score was significantly reduced by antihypertensive therapy (P<.01) and lipid-lowering therapy (P<.05) . Glomerular injury score was lowest in animals receiving combined the rapy, reflecting an interaction between these therapies (P<.01) (untre ated, 173+/-29; Lova, 128+/-24; AH, 111+/-22; AH/Lova, 48+/-11). Our r esults suggest that both hypertension and hyperlipidemia accelerate gl omerular sclerosis in experimental glomerulonephritis and that combine d therapy of these disorders may best limit progressive renal injury.