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Functional and histological improvement after everolimus rescue of chronic
allograft dysfunction in renal transplant recipients
#MMPMID26056462
Chow KM
; Szeto CC
; Lai FM
; Luk CC
; Kwan BC
; Leung CB
; Li PK
Ther Clin Risk Manag
2015[]; 11
(?): 829-35
PMID26056462
show ga
BACKGROUND: We tested the strategy of mTOR inhibitors with calcineurin inhibitor
minimization in renal transplant recipients with known chronic allograft
dysfunction. METHODS: In this open-label, single-arm study, renal transplant
patients were recruited after biopsy-confirmed chronic allograft dysfunction in
the absence of acute rejection episode within 2 months, with proteinuria <0.8
g/day, and serum creatinine <220 ?mol/L or estimated glomerular filtration rate
>40 mL/min/1.73 m(2). They were converted to everolimus (aiming for trough
everolimus level 3-8 ng/mL) with cyclosporine minimization, to assess the effect
on renal function, rate of glomerular filtration rate decline, and longitudinal
transplant biopsy at 12 months. RESULTS: Seventeen Chinese patients (median
transplant duration, 4.2 years) were recruited; no patients discontinued study
medication. The mean slope of the glomerular filtration rate over time was
-4.31±6.65 mL/min/1.73 m(2) per year in the year before everolimus, as compared
with 1.29±5.84 mL/min/1.73 m(2) per year in the 12 months of everolimus therapy,
a difference of 5.61 mL/min/1.73 m(2) per year (95% confidence interval [CI],
0.40-10.8) favoring everolimus therapy (P=0.036). Serial renal biopsy histology
showed significant decrease of tubular atrophy (15.7%±11.3% versus 7.1%±7.3%,
P=0.005) and interstitial fibrosis (14.8%±11.5% versus 7.2%±8.2%, P=0.013).
Intrarenal expression of TGF-?1 mRNA showed a nonsignificant decrease after
everolimus treatment. CONCLUSION: In renal transplant recipients with
biopsy-confirmed chronic allograft dysfunction, we found a significant beneficial
effect of everolimus rescue therapy and calcineurin inhibitor minimization
strategy on the improvement of glomerular filtration rate decline rate. In
secondary analysis, everolimus was shown to slow down the disease progression by
reducing the tubular atrophy and interstitial fibrosis scoring.