title: mToR inhibitors-induced proteinuria: mechanisms, significance, and management.
abstract: Massive urinary protein excretion has been observed after conversion from calcineurin inhibitors to mammalian target of rapamycin (mToR) inhibitors, especially sirolimus, in renal transplant recipients with chronic allograft nephropathy. Because proteinuria is a major predictive factor of poor transplantation outcome, many studies focused on this adverse event during the past years. Whether proteinuria was due to sirolimus or only a consequence of calcineurin inhibitors withdrawal remained unsolved until high range proteinuria has been observed during sirolimus therapy in islet transplantation and in patients who received sirolimus de novo. Podocyte injury and focal segmental glomerulosclerosis have been related to mToR inhibition in some patients, but the pathways underlying these lesions remain hypothetic. We discuss herein the possible mechanisms and the significance of mToR blockade-induced proteinuria.
authors.affiliation: Transplantation Unit, Hôpital Necker, 75743 Paris, France. emmanuel.letavernier@tnn.ap-hop-paris.fr
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Letavernier
authors.forename: Christophe
authors.initials: C
authors.lastname: Legendre
mesh_terms: D001707:Biopsy, Needle; D065095:Calcineurin Inhibitors; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation; D011494:Protein Kinases / Q000378:metabolism; D011507:Proteinuria / Q000139:chemically induced*; D051437:Renal Insufficiency / Q000473:pathology; D020123:Sirolimus / Q000009:adverse effects* / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases
chemical_list: D065095:Calcineurin Inhibitors; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus