Dietary protein restriction and glomerular permselectivity in nephrotoxic serum nephritis

We have previously demonstrated that long-term dietary protein restriction ameliorates proteinuria and limits glomerular structural injury in rats with nephrotoxic serum nephritis. In the present study, we examined the influence of short-term dietary protein restriction on glomerular permselectivity. As compared to nephritic rats maintained on a normal protein diet, whole kidney and single nephron hemodynamics were lower in nephritic rats subjected to dietary protein restriction of three days duration (glomerular filtration rate: 0.79 ± 0.10 vs. 1.46 ± 0.11 ml/min, P < 0.003; renal plasma flow rate: 2.50 ± 0.34 vs. 3.96 ± 0.38 ml/min, P < 0.02; glomerular capillary pressure: 44 ± 1 vs. 53 ± 1 mm Hg, P < 0.002; proteinuria: 77 ± 15 vs. 224 ± 14 mg/24 hr, P < 0.01). This was associated with a rise in afferent resistance, from 2.99 ± 0.77 to 5.45 ± 0.94 dyn · sec · cm^-5, NS. In nephritic rats maintained on 24% protein, fractional clearances were elevated above control values for neutral dextrans with molecular radii exceeding 50 Å but were depressed for those with molecular radii below 30 Å (P < 0.05). Dietary protein restriction elevated the fractional clearances of dextrans with radii <30 Å while depressing the fractional clearances of dextrans with radii >50 Å (P < 0.05). The proportion of glomerular filtrate permeating the shunt pathway was elevated above control values in nephritic rats on the 24% protein diet but declined in those fed the low protein diet (NSN-24%: 0.86%; NSN-6%: 0.31%; control: 0.19%). In conclusion, renal hemodynamics are impaired, proteinuria is reduced and glomerular size-selective barrier dysfunction is ameliorated by short-term dietary protein restriction in nephrotoxic serum nephritis. The reduction in proteinuria is mediated both by a decline in glomerular filtration rate and by improved glomerular size permselectivity due to reduced utilization of the shunt pathway.