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Loss of Nephrin Expression in Glomeruli of Kidney‐Transplanted Patients Under m‐TOR Inhibitor Therapy
Author(s) -
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 G. P.
Publication year - 2010
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2010.03259.x
Subject(s) - nephrin , medicine , proteinuria , kidney , slit diaphragm , urology , sirolimus , podocyte , biopsy
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.