జర్నల్ ఆఫ్ నెఫ్రాలజీ & థెరప్యూటిక్స్

Effect of Spironolactone on Chronic Allograft Nephropathy in Rats

Abstract

Steven M. Cogar, Chad W. Schmiedt, Cathy A. Brown, Michel L. Vandenplas, Christy Chessman and David J. Hurley

Objective: Chronic allograft nephropathy (CAN) is common following renal transplantation in cats and people. Aldosterone potentiates ongoing renal injury; however its role in CAN is less defined. Spironolactone, an aldosterone receptor blocker, is protective in other rodent models of renal injury. The purpose of this study was to evaluate spironolactone on the development of CAN in a rat model
Animals: Fisher and Lewis, adult, male rats.
Procedures: A Lewis to Fisher model of CAN was used. Rats were divided into 4 groups, 2 nephrectomy controls (CON) and 2 transplantation (TX) groups. Two groups (a CON and TX) received tap water (0.25 ml/day orally), and the remaining 2 received spironolactone (10 mg/kg orally) daily for 16 weeks post transplantation. Serum creatinine concentration, urine-protein: urine-creatinine (UP: UC), and changes in renal cortex gene expression were measured during and at 16 weeks after transplantation.
Results: There were no significant differences in any of the outcome measures when the 2 TX groups were compared. TX rats had significantly more (p=0.0002) histological lesions consistent with CAN and elevation in TNF-α (p=0.0402) compared to CON animals.
Conclusions and clinical relevance: In this study, spironolactone did not protect against the development or progression of CAN.
Impact for human medicine: The impact of aldosterone on the occurrence of CAN in humans following renal transplantation remains an area of investigation.