Using a recently described rodent model of chronic cyclosporine nephropathy (CCN), the effects of uninephrectomy (UNx) and high protein feeding on the development of CCN were studied. After 28 days of i.p. cyclosporine (Cs; 25 mg/kg/day) in UNx and sham nephrectomized (SNx) rats, the single kidney GFR was higher in UNx animals (0.55 ± 0.09 vs. 0.29 ± 0.05 ml/min, P < 0.04) as was RPF (3.05 ± 0.46 vs. 1.45 ± 0.37 ml/min, P < 0.04). Morphometric evaluation of the chronic tubulointerstitial lesion (TI) demonstrated lower scores and relative protection in the UNx group (16.48 ± 3.52 vs. 64.76 ± 18.30, P < 0.01). In separate groups of rats undergoing UNx or SNx and subsequent treatment with Cs, dry kidney weights confirmed that compensatory renal hypertrophy was present in UNx animals. The modulating effect of dietary protein on the lesion of CCN was studied in UNx rats fed a 5% or 60% protein diet during the period of Cs treatment. At the end of the study period animals fed the high protein diet demonstrated a higher RPF (3.19 ± 0.58 vs. 1.58 ± 0.29 ml/min, P < 0.04), higher GFR (0.55 ± 0.07 vs. 0.35 ± 0.04 ml/min, P < 0.05) and lower TI score (64.45 ± 17.35 vs. 130.32 ± 23.48, P < 0.04) when compared with animals consuming a low protein diet. We conclude that the relative renal vasodilation induced by partial ablation of renal mass and high protein feeding affords some protection against the development of CCN.
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