Effects of Low Protein Intake on the Development of the Remaining Kidney in Subtotally Nephrectomized Immature Rats: Apoptosis and Epidermal Growth Factor

Abstract

Effects of low protein intake on the development of the remaining kidney in subtotally (5/6) nephrectomized immature rats were examined. Three week-old weaning rats were kept on a diet containing either 12% (Lp rats) or 18% (Np rats) protein for 4 or 8 weeks after subtotal nephrectomy. Blood urea nitrogen (BUN) concentration was determined at 2, 4, 6, and 8 weeks after 5/6 nephrectomy. At 4 or 8 weeks after the operation, glomerular sclerosis and tubulointerstitial damage were assessed by a standard semiquantitative analysis and were expressed as the glomerular sclerosis index (GSI) and interstitial fibrosis score (IFS), respectively. The localization of DNA fragmented cells in the kidney was examined by the terminal deoxynucleotidyl transferase (TdT) -mediated d-UTP-biotin nick end labeling (TUNEL) method and the localization of the epidermal growth factor (EGF) by immunohistochemical methods. BUN concentration was significantly lower in the Lp rats compared with that in the Np rats. Both 4 and 8 weeks after subtotal nephrectomy, GSI and incidence of TUNEL positive cells in the distal tubules were significantly lower in the Lp rats than in the Np rats. Four weeks after the operation, IFS was significantly lower in the Lp rats than in the Np rats. Four and 8 weeks after the operation, EGF positive cells in the distal tubules were more observed in the Lp rats than in the Np rats. These findings reveal that protein restriction is effective in preventing renal tubular scarring in immature rats and that EGF is involved in the process of this prevention.