title: Advanced IgA nephropathy with impaired renal function benefits from losartan treatment in rats.
abstract: BACKGROUND
  Treatment with angiotensin receptor blockers (ARBs) is successful in mitigating IgA nephropathy (IgAN), independent of blood pressure changes, but the therapeutic role of ARB in advanced IgAN with impaired renal function is to be ascertained. The present study was performed to investigate the effect of losartan on advanced IgAN induced by staphylococcal enterotoxin B (SEB) combined with 5/6 nephrectomy in rats.
  
  
  METHODS
  Fifty-four male SD rats were randomly divided into three group: Rats in the model group were treated with SEB plus 5/6 nephrectomy, and those in the losartan group were gavaged with losartan (33.3 mg kg(-1 )d(-1)) besides the treatment with SEB plus 5/6 nephrectomy. The urine and blood biochemical changes of rats were tested. IgA, IgG, IgM and C3 depositions were studied dynamically with immunofluorescence. The renal tissue structures were observed under light microscopy. The expressions of TGF-β1, FN, alpha-SMA and FGF-1 in rat renal tissues were determined with immunohistochemical methods and real-time PCR.
  
  
  RESULTS
  At 12 weeks, rats with SEB treatment plus 5/6 nephrectomy showed gradually increased urinary red blood cell (URBC) with a gradual elevation of the 24 h urinary protein, serum BUN and Scr, but losartan treatment lowered the levels of 24 h urinary protein, serum BUN and Scr. A large number of IgA depositions in the mesangial area, glomerulosclerosis and tubulointerstitial fibrosis were found in the model group, and the losartan group showed relieved injury. The expressions of TGF-β1, FN, alpha-SMA and FGF-1 were significantly elevated in the model. Losartan lessened their expressions.
  
  
  CONCLUSIONS
  Losartan treatment can delay the progression of advanced IgA nephropathy with impaired renal function.
authors.affiliation: Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Wencheng
authors.initials: W
authors.lastname: Fu
authors.forename: Zhouhui
authors.initials: Z
authors.lastname: Jin
authors.forename: Yunman
authors.initials: Y
authors.lastname: Wang
authors.forename: Weiguo
authors.initials: W
authors.lastname: Yao
authors.forename: Peihao
authors.initials: P
authors.lastname: Yin
authors.forename: Wen
authors.initials: W
authors.lastname: Peng
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D004353:Drug Evaluation, Preclinical; D004768:Enterotoxins; D005922:Glomerulonephritis, IGA / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D007677:Kidney Function Tests / Q000379:methods; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D015415:Biomarkers; D004768:Enterotoxins; C031818:enterotoxin B, staphylococcal; D019808:Losartan