Progression of graft fibrosis under mammalian target of rapamycin inhibitor-based regimen.
OBJECTIVE
Nephrotoxic potential of mammalian target of rapamycin inhibitors (mTORi) is different from calcineurin inhibitors (CNI). The aim of this study is to investigate the interstitial fibrosis (ci) and tubular atrophy (ct) progression from the baseline to first year under a mTORi-based, CNI-free regimen.


METHODS
Thirty-five kidney transplant recipients who had to have adequate baseline and first year protocol biopsy were enrolled. Exclusion criteria were: the replacement of CNI at any time; acute deterioration in allograft functions; and serum creatinine level above 3 mg/dL at 12 months. Banff criteria were used for histopathological classification. Progression was defined as delta ci + ct ≥ 2 (difference between 12th month and baseline).


RESULTS
Mean age of patients and donors were 34 ± 11 and 49 ± 10 years. Twelve patients had delayed graft function (DGF). The maintenance regimen consisted of sirolimus (n = 24) and everolimus (n = 11) with mycophenolate mofetil and steroids. Incidence of acute rejection was 25.7%. At baseline, the incidence of nil and mild fibrosis were 80% and 20%, respectively. At 12 months, 17.1% of patients had moderate, 40% had mild and 42.9% had nil fibrosis. Histological progression from baseline to first year was present in 34% of patients. In multivariate analysis the presence of DGF (P = 0.018) and deceased donor type (P = 0.011) were the most important predictors for fibrosis progression.


CONCLUSIONS
Progression of graft fibrosis may be seen in one-third of patients under a mTORi-based regimen particularly manifested in deceased donor recipients with subsequent DGF.
Yilmaz
Mumtaz
M
Nephrology Department, Ege University, Bornova, Turkey. mumt@hotmail.com
Nart
Ahmet
A
Sen
Sait
S
Tasli
Funda
F
Uslu
Adam
A
Hur
Ender
E
Ozkahya
Mehmet
M
Hoscoskun
Cuneyt
C
Toz
Huseyin
H
D000328:Adult; D001284:Atrophy; D001706:Biopsy; D016009:Chi-Square Distribution; D051799:Delayed Graft Function / Q000209:etiology; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005355:Fibrosis; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology; D016030:Kidney Transplantation / Q000009:adverse effects*; D016015:Logistic Models; D008875:Middle Aged; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D013997:Time Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014421:Turkey; D055815:Young Adult
D007166:Immunosuppressive Agents; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases