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Use of the mTOR inhibitor (mTORi) sirolimus to replace calcineurin inhibitors in kidney transplantation has been associated with improved renal function but, in a proportion of cases, also with de novo or exacerbated proteinuria. Experimental deficiency of vascular endothelial growth factor (VEGF) induces proteinuria and mTOR is required for VEGF production and signalling. We therefore explored the impact of sirolimus on the development of chronic allograft dysfunction (CAD) in the rat, with a focus on VEGF biology.

nephrology, dialysis, transplantation/nephrology dialysis transplantation

Sirolimus reduces vasculopathy but exacerbates proteinuria in association with inhibition of VEGF and VEGFR in a rat kidney model of chronic allograft dysfunction