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Open Access Research article

Mycophenolate mofetil and FK506 have different effects on kidney allograft fibrosis in rats that underwent chronic allograft nephropathy

Lei Luo1, Zhaolin Sun2, Weidong Wu1 and Guangheng Luo2*

Author Affiliations

1 Department of Research and Education, Guizhou Province People’s Hospital, Guiyang, China

2 Department of Urology Surgery, Guizhou Province People’s Hospital, Guiyang, China

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BMC Nephrology 2012, 13:53  doi:10.1186/1471-2369-13-53

Published: 2 July 2012

Abstract

Background

Tacrolimus (FK506) is associated with renal fibrosis in long-term use. Mycophenolatemofetil (MMF) can also inhibit or attenuate the progression of renal fibrosis. This study aimed to determine the different effects of FK506 and MMF on fibrosis-associated genes in the kidney in rats that underwent chronic allograft nephropathy (CAN).

Methods

Fisher (F344) kidneys were orthotopically transplanted into Lewis rat recipients. All recipients were given Cyclosporin A (CsA) 10 mg/kg-1.d-1 × 10 day and were then randomly divided into three oral treatment groups (n = 9 in each group): (1) the vehicle group was given vehicle orally; (2) the FK506 group was given 0.15 mg/kg-1.d-1 FK506; and (3) the MMF group was given 20 mg/kg-1.d-1 MMF. At 4, 8, and 12 weeks post-transplantation, serum creatinine (SCr), collagen deposition, Connective tissue growth factor (CTGF), alpha smooth muscle actin (α-SMA) and E-cadherin expressions were determined and hematoxylin-eosin (HE) and Periodic acid-Schiff (PAS) stains were performed.

Results

Renal function progressively deteriorated and showed typical CAN morphology in the vehicle and FK506 groups, while SCr and inflammatory infiltration (Banff score) showed a significant decrease in the MMF group after 8 weeks post-transplantation compared with those in the other groups (p < 0.05). Furthermore, expression levels of CTGF and α-SMA in the MMF group were significantly reduced, and the down-regulated expression of E-cadherin was abated (p < 0.05).

Conclusions

MMF showed favorable effects on renal interstitial fibrosis, thus efficiently retarding the progression of CAN.

Keywords:
Tacrolimus; Mycophenolate Mofetil; Renal fibrosis; Chronic allograft nephropathy; Kidney transplantation