Low protein diet mediated renoprotection in remnant kidneys: Renal autoregulatory versus hypertrophic mechanisms

Abstract

Background. The mechanism of low protein diet conferred renoprotection in the ablation model remains controversial. Blockade of glomerular hypertrophy, reduced preglomerular vasodilation, and preserved autoregulation have all been postulated. The potential differential impact of calcium channel blockers on these mechanisms and glomerulosclerosis was examined. Methods. Rats with 5/6 renal ablation received either a 25% standard protein diet, an 8% low protein diet and a low protein diet with either verapamil or amlodipine. Renal autoregulatory and morphometric studies were performed at 3 weeks before the development of significant injury, and the assessment of glomerulosclerosis after 7 weeks of continuous blood pressure radiotelemetry in additional rats. Results. The preserved renal autoregulation in low protein rats was abolished by both calcium channel blockers, with the impairment being either comparable to (low protein + verapamil) or greater than the standard protein rats (low protein + amlodipine). Neither calcium channel blocker blocked the inhibitory effects of low protein diet on renal blood flow, kidney weight, and glomerular volume. Results (mean ± SE) for glomerular volume (μm-3 × 10-6): low protein (N = 11), 1.6 ± 0.1; low protein + verapamil (N = 10), 1.7 ± 0.1; low protein + amlodipine (N = 12), 1.7 ± 0.2; versus standard protein (N = 10), 2.2 ± 0.1; P < 0.05. Only amlodipine, but not verapamil, reduced average systolic blood pressure (143 ± 2 mm Hg versus low protein rats, 168 ± 5 mm Hg, and standard rats, 170 ± 6 mm Hg; P < 0.01). Nevertheless, the glomeruloprotection seen in low protein (N = 15) as compared to standard protein (N = 14) rats (9% ± 3% versus 28% ± 6% glomerulosclerosis; P < 0.01) was abolished in both low protein + verapamil (N = 14, 32% ± 7%) and low protein + amlodipine rats (N = 16, 27% ± 7%). Conclusions. Preservation of renal autoregulation and not inhibition of hypertrophy is the critical component in low protein diet-conferred glomeruloprotection.