Loss of nephrin expression in glomeruli of kidney-transplanted patients under m-TOR inhibitor therapy.
Articolo
Data di Pubblicazione:
2010
Abstract:
The development of proteinuria has been observed in kidney-transplanted patients on m-TOR inhibitor (m-TORi) treatment. Recent studies suggest that m-TORi(s) may alter the behavior and integrity of glomerular podocytes. We analyzed renal biopsies from kidney-transplanted patients and evaluated the expression of nephrin, a critical component of the glomerular slit-diaphragm. In a group of patients on 'de novo' m-TORi-treatment, the expression of nephrin within glomeruli was significantly reduced in all cases compared to pretransplant donor biopsies. Biopsies from control transplant patients not treated with m-TORi(s) failed to present a loss of nephrin. In a group of patients subsequently converted to m-TORi-treatment, a protocol biopsy performed before introduction of m-TORi was also available. The expression of nephrin in the pre-m-TORi biopsies was similar to that observed in the pretransplant donor biopsies but was significantly reduced after introduction of m-TORi(s). Proteinuria increased after the m-TORi inititiation in this group. However, in some cases proteinuria remained normal despite reduction of nephrin. In vitro, sirolimus downregulated nephrin expression by human podocytes. Our results suggest that m-TORi(s) may affect nephrin expression in kidney-transplanted patients, consistently with the observation in vitro on cultured podocytes.
Tipologia CRIS:
03A-Articolo su Rivista
Keywords:
kidney transplantation; nephrin; m-TOR inhibitor
Elenco autori:
Biancone L; Bussolati B; Mazzucco G; Barreca A; Gallo E; Rossetti M; Messina M; Nuschak B; Fop F; Medica D; Cantaluppi V; Camussi G; Segoloni GP.
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