title: SRL-based immunosuppression vs. CNI minimization in pediatric renal transplant recipients with chronic CNI nephrotoxicity.
abstract: Because calcineurin inhibitor (CNI)-induced nephrotoxicity contributes significantly to late renal allograft loss, sirolimus (SRL)-based, CNI-free maintenance immunosuppression has been advocated, but data in the pediatric population are scarce. We therefore analyzed the efficacy and safety of an SRL-based immunosuppressive regimen plus mycophenolate mofetil (MMF) and corticosteroids vs. CNI minimization (mean dose reduction by 39%) plus MMF and corticosteroids in 19 pediatric recipients with biopsy-proven CNI-induced nephrotoxicity in a single-center case-control study. In the SRL group, we observed, one yr after study entry, an improvement of glomerular filtration rate (GFR) by 10.3 +/- 3.0 mL/min/1.73 m2 (p < 0.05 vs. baseline) in seven of 10 patients and a stabilization in the remaining three, while in the CNI minimization group GFR improved by 17.7 +/- 7.1 mL/min/1.73 m2 (p < 0.05) in six of nine recipients and stabilized in the remaining three. No patient in either group experienced an acute rejection episode. The main adverse event under SRL therapy was a transient hyperlipidemia in 70% of patients. In pediatric renal transplant recipients with declining graft function because of CNI-induced nephrotoxicity, CNI withdrawal and switch to SRL-based therapy or CNI minimization are associated with a comparable improvement of GFR after 12 months of observation.
authors.affiliation: Division of Pediatric Nephrology, University Children's Hospital Heidelberg, Im Neuenheimer Feld, Heidelberg, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Höcker
authors.forename: Reinhard
authors.initials: R
authors.lastname: Feneberg
authors.forename: Sabine
authors.initials: S
authors.lastname: Köpf
authors.forename: Lutz T
authors.initials: LT
authors.lastname: Weber
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Waldherr
authors.forename: Elke
authors.initials: E
authors.lastname: Wühl
authors.forename: Burkhard
authors.initials: B
authors.lastname: Tönshoff
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000009:adverse effects; D000704:Analysis of Variance; D016022:Case-Control Studies; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D016030:Kidney Transplantation; D008297:Male; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D011446:Prospective Studies; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects*; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D020123:Sirolimus