title: Loss of nephrin expression in glomeruli of kidney-transplanted patients under m-TOR inhibitor therapy.
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.
authors.affiliation: Division of Nephrology Dialysis and Transplantation, Department of Internal Medicine, San Giovanni Battista Hospital and University of Torino, Italy. luigi.biancone@unito.it
authors.forename: L
authors.initials: L
authors.lastname: Biancone
authors.forename: B
authors.initials: B
authors.lastname: Bussolati
authors.forename: G
authors.initials: G
authors.lastname: Mazzucco
authors.forename: A
authors.initials: A
authors.lastname: Barreca
authors.forename: E
authors.initials: E
authors.lastname: Gallo
authors.forename: M
authors.initials: M
authors.lastname: Rossetti
authors.forename: M
authors.initials: M
authors.lastname: Messina
authors.forename: B
authors.initials: B
authors.lastname: Nuschak
authors.forename: F
authors.initials: F
authors.lastname: Fop
authors.forename: D
authors.initials: D
authors.lastname: Medica
authors.forename: V
authors.initials: V
authors.lastname: Cantaluppi
authors.forename: G
authors.initials: G
authors.lastname: Camussi
authors.forename: G P
authors.initials: GP
authors.lastname: Segoloni
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008565:Membrane Proteins / Q000096:biosynthesis*; D008875:Middle Aged; D050199:Podocytes / Q000378:metabolism; D011507:Proteinuria / Q000139:chemically induced; D012189:Retrospective Studies; D020123:Sirolimus / Q000009:adverse effects*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D008565:Membrane Proteins; C113267:nephrin; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus