title: Sirolimus-associated heavy proteinuria in a renal transplant recipient: evidence for a tubular mechanism.
abstract: Sirolimus is a new and potent immunosuppressive agent. Recently, increased proteinuria has been recognized as an important complication. However, the mechanism thereof has remained unclear. We describe a patient who received sirolimus as standard therapy after living donor kidney transplantation. Within 10 days the patient developed a severe proteinuria that disappeared completely after substituting tacrolimus for sirolimus. Renal biopsy disclosed normal glomeruli even without effacement of the podocytic foot processes. Using FITC labeled anti-albumin antibodies we noted complete absence of albumin in the proximal tubules, whereas an abundant albumin staining was observed in a control patient with a comparable level of proteinuria due to a recurrence of focal segmental glomerulosclerosis after transplantation. Our data suggest that sirolimus can induce severe proteinuria, and that reduced tubular protein reabsorption contributes to the protein loss.
authors.affiliation: Department of Nephrology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Straathof-Galema
authors.forename: J F M
authors.initials: JF
authors.lastname: Wetzels
authors.forename: H B P M
authors.initials: HB
authors.lastname: Dijkman
authors.forename: E J
authors.initials: EJ
authors.lastname: Steenbergen
authors.forename: L B
authors.initials: LB
authors.lastname: Hilbrands
mesh_terms: D001706:Biopsy; D003404:Creatinine / Q000097:blood; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000502:physiology; D007684:Kidney Tubules / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000139:chemically induced*; D020123:Sirolimus / Q000009:adverse effects*
chemical_list: D007166:Immunosuppressive Agents; D003404:Creatinine; D020123:Sirolimus