title: Effect of sirolimus withdrawal in patients with deteriorating renal function.
abstract: Sirolimus has been an important addition to immunosuppressive regimens utilized in kidney transplantation. However, sirolimus can potentiate calcineurin inhibitor (CNI) nephrotoxicity by some still uncertain mechanisms. Studies have demonstrated that withdrawal of a CNI under sirolimus immunosuppression can improve renal function. However, it has yet to be demonstrated that withdrawal of sirolimus from such a regimen can also improve renal function and reverse progressive functional deterioration. We studied 17 patients who developed deterioration of renal function while on a CNI and sirolimus. Once an established deterioration in renal function was noted, sirolimus was withdrawn from the regimen and replaced with mycophenolate mofetil. Out of 17 patients with a negative slope in 1/cr, 15 demonstrated a positive treatment effect (change to a positive slope). On aggregate, renal function improved by 18% (creatinine 2.75-2.24 mg/dL), LDL cholesterol improved, as did hematocrit values after withdrawal. The majority of patients on a CNI and sirolimus regimen who experience deterioration in renal function demonstrate improvement in renal function after withdrawal of sirolimus. This strategy may be particularly useful in those patients where CNI withdrawal is considered to be of high immunologic or metabolic risk.
authors.affiliation: University of Florida, Gainesville, FL 32610-0224, USA. kaplab@medicine.ufl.edu
authors.forename: Bruce
authors.initials: B
authors.lastname: Kaplan
authors.forename: Jesse
authors.initials: J
authors.lastname: Schold
authors.forename: Titte
authors.initials: T
authors.lastname: Srinivas
authors.forename: Karl
authors.initials: K
authors.lastname: Womer
authors.forename: David P
authors.initials: DP
authors.lastname: Foley
authors.forename: Pamela
authors.initials: P
authors.lastname: Patton
authors.forename: Richard
authors.initials: R
authors.lastname: Howard
authors.forename: Herwig-Ulf
authors.initials: HU
authors.lastname: Meier-Kriesche
mesh_terms: D000328:Adult; D065095:Calcineurin Inhibitors; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects*; D016030:Kidney Transplantation; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D051437:Renal Insufficiency / Q000139:chemically induced; D020123:Sirolimus / Q000494:pharmacology*; D013997:Time Factors; D028761:Withholding Treatment
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D003404:Creatinine; D009173:Mycophenolic Acid; D020123:Sirolimus