title: Mycophenolate mofetil and FK506 have different effects on kidney allograft fibrosis in rats that underwent chronic allograft nephropathy.
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.
authors: Department of Research and Education, Guizhou Province People's Hospital, Guiyang, China.
authors: Lei
authors: L
authors: Luo
authors: Zhaolin
authors: Z
authors: Sun
authors: Weidong
authors: W
authors: Wu
authors: Guangheng
authors: G
authors: Luo
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004347:Drug Interactions; D005355:Fibrosis / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D007166:Immunosuppressive Agents / Q000009:adverse effects; D007674:Kidney Diseases / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control*; D016030:Kidney Transplantation / Q000009:adverse effects*; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D016559:Tacrolimus / Q000009:adverse effects*; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus