title: Histological progression of chronic renal allograft injury comparing sirolimus and mycophenolate mofetil-based protocols. A single-center, prospective, randomized, controlled study.
abstract: In an effort to mitigate progression of IF/TA associated with chronic renal allograft injury, we hypothesize that adjuvant immunosuppression with sirolimus (SRL) will delay progression compared with MMF. Subjects 5-17 yr old, >1-yr post-transplant with mild or moderate IF/TA (Banff criteria) and tacrolimus dose minimization were randomized to continue MMF or convert to SRL and followed for two yr. For the entire cohort (n = 20), there was significant progression of %GGS, ci, ct, cv, and ah scores over the follow-up period (p < 0.05). There was no difference in rates of progression of Banff scores, %GGS, or % IF over two yr between the two groups, though power was low. Both groups exhibited similar rates of eGFR decline (MMF: -12.3 vs. SRL: -11.8 mL/min/1.73 m²/yr), which was correlated with ct score (p < 0.05). The SRL group had more episodes of acute allograft dysfunction and oral ulcers. Proteinuria at 24 months was significantly increased in the SRL group (6/9 subjects) but was not correlated with eGFR or %GGS. We conclude that neither MMF nor SRL, combined with low-dose tacrolimus, was effective at mitigating progressive histological changes or functional decline associated with chronic renal allograft injury.
authors.affiliation: Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada. tblydthansen@hsc.mb.ca
authors.forename: Tom D
authors.initials: TD
authors.lastname: Blydt-Hansen
authors.forename: Ian W
authors.initials: IW
authors.lastname: Gibson
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Birk
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000628:therapy*; D016559:Tacrolimus / Q000627:therapeutic use; D013997:Time Factors; D014184:Transplantation, Homologous / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus