Mammalian Target of Rapamycin Inhibition Halts the Progression of Proteinuria in a Rat Model of Reduced Renal Mass

F. Diekmann, J. Rovira, J. Carreras, E. M. Arellano, E. Banon-Maneus, M. J. Ramirez-Bajo, A. Gutierrez-Dalmau, M. Brunet, J. M. Campistol
2007 Journal of the American Society of Nephrology  
Many kidney transplant patients experience an increase in proteinuria when converted from a calcineurin inhibitor-based regimen to one based on a mammalian target of rapamycin (mTOR) inhibitor, and preexisting proteinuria and poor renal function have been identified as risk factors for this increase. Our aim was to evaluate the effect of sirolimus, an mTOR inhibitor, on renal function and histology in a proteinuric model of reduced renal mass. Sirolimus-treated animals had approximately half as
more » ... much proteinuria as vehicle-treated animals (P Ͻ 0.05), and had less glomerulosclerosis, tubular atrophy, interstitial fibrosis, and inflammation. Immunohistochemistry showed that sirolimus attenuated the increased expression of renal vascular endothelial growth factor (VEGF), as well as the expression of VEGF receptors 1 and 2. In conclusion, sirolimus halted the progression of proteinuria and structural damage in a rat model of reduced renal mass, possibly through a reduction in renal VEGF activity.
doi:10.1681/asn.2007010087 pmid:17804674 fatcat:yneijql6ibcdjmtzcp67xiiwli