Abstract
BackgroundTacrolimus (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).MethodsFisher (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.ResultsRenal 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).ConclusionsMMF showed favorable effects on renal interstitial fibrosis, thus efficiently retarding the progression of CAN.
Highlights
Tacrolimus (FK506) is associated with renal fibrosis in long-term use
Research has demonstrated that more than 50 % of all renal transplants have graft failure, due to end-stage renal failure [2]. This process of renal failure was formerly known as chronic allograft nephropathy (CAN), which was originally coined as a histological grading of the extent of interstitial fibrosis (IF) and tubular atrophy (TA) present in biopsies in 1991
The Banff score in the MMF group was lower at 4 weeks compared with the vehicle and FK506 groups, but this was not significant (p > 0.05)
Summary
Tacrolimus (FK506) is associated with renal fibrosis in long-term use. Mycophenolatemofetil (MMF) can 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). Research has demonstrated that more than 50 % of all renal transplants have graft failure, due to end-stage renal failure [2] This process of renal failure was formerly known as chronic allograft nephropathy (CAN), which was originally coined as a histological grading of the extent of interstitial fibrosis (IF) and tubular atrophy (TA) present in biopsies in 1991. A number of short- and long-term animal and human studies on kidney allografts have demonstrated the nephrotoxicity of tacrolimus [6,7]. Reduced dosing or withdrawal of tacrolimus, or addition of mycophenolatemofetil (MMF) in patients generally results in less progression in chronic allograft nephropathy (CAN) indices [8]. It has been reported that MMF can ameliorate transplant fibrosis in an experimental animal CAN model [10,11]
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