Key result
Spironolactone administered at 10 mg/kg daily for 16 weeks did not improve renal allograft function, alter pro-inflammatory gene expression, or reduce microscopic lesions characteristic of chronic allograft nephropathy compared to water.
Why the study?
The role of aldosterone in chronic allograft nephropathy (CAN) is less defined, and the effect of spironolactone on CAN development needed evaluation.
Does spironolactone prevent the development or progression of chronic allograft nephropathy in a rat model of renal transplantation?
Does spironolactone prevent the development or progression of chronic allograft nephropathy in a rat model of renal transplantation?
In a rat model of renal transplantation, spironolactone at 10 mg/kg/day did not protect against the development or progression of chronic allograft nephropathy.
Spironolactone lacks benefit in this rat allograft model; leaves open aldosterone blockade efficacy for chronic allograft nephropathy in humans.
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.
No takes yet. Share an insight, caveat, or question.
Steven M. Cogar (2012) studied Chronic allograft nephropathy (n=24). Spironolactone vs. Tap water (0.25 ml/day orally) was evaluated on Development of chronic allograft nephropathy (measured by serum creatinine, UP:UC, gene expression, and histology). Spironolactone administered at 10 mg/kg daily for 16 weeks did not improve renal allograft function, alter pro-inflammatory gene expression, or reduce microscopic lesions characteristic of chronic allograft nephropathy compared to water.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: