title: Early brief treatment with losartan plus mycophenolate mofetil provides lasting renoprotection in a renal ablation model.
abstract: BACKGROUND
  Inflammatory events antecede established renal injury in rats with 5/6 renal ablation (Nx), as indicated by the beneficial effects of early, uninterrupted treatment with mycophenolate mofetil (MMF). Angiotensin II also exerts a major pathogenic role at this initial phase. We investigated whether losartan (L) or L+MMF treatment, started early, and L+MMF treatment, started late, would exert lasting renoprotection in Nx even after being discontinued.
  
  
  METHODS
  Adult male Munich-Wistar rats underwent Nx and were divided into three groups: Nx (untreated), Nx(L) (given L), and Nx(LMMF) (given L and MMF). Protocol 1: treatments began on day 1, and ceased on day 30, after Nx. Protocol 2: L+MMF treatment began on day 30 and ceased on day 60.
  
  
  RESULTS
  Protocol 1: on day 30, hypertension, albuminuria and renal injury were strongly attenuated in Groups Nx(L) and Nx(LMMF). On day 120, these abnormalities were still attenuated in group Nx(LMMF). Protocol 2: on day 120, all parameters were similar between this late Nx(LMMF) group and untreated Nx.
  
  
  CONCLUSIONS
  In Nx, temporary suppression of early, transitory hemodynamic/inflammatory phenomena affords relatively durable renoprotection even after treatment discontinuation. This effect is not obtained with similar temporary treatment initiated later in the course of renal disease.
authors.affiliation: Department of Clinical Medicine, University of São Paulo School of Medicine, Brazil.
authors.forename: Clarice Kazue
authors.initials: CK
authors.lastname: Fujihara
authors.forename: Jose Mauro
authors.initials: JM
authors.lastname: Vieira
authors.forename: Claudia Ramos
authors.initials: CR
authors.lastname: Sena
authors.forename: Bianca Helena
authors.initials: BH
authors.lastname: Ventura
authors.forename: Denise Maria
authors.initials: DM
authors.lastname: Malheiros
authors.forename: Roberto
authors.initials: R
authors.lastname: Zatz
mesh_terms: D000419:Albuminuria / Q000517:prevention & control; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002908:Chronic Disease; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D007674:Kidney Diseases / Q000473:pathology / Q000503:physiopathology*; D019808:Losartan / Q000008:administration & dosage / Q000627:therapeutic use*; D008264:Macrophages / Q000187:drug effects; D008297:Male; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009392:Nephrectomy; D020011:Protective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000893:Anti-Inflammatory Agents; D020011:Protective Agents; D009173:Mycophenolic Acid; D019808:Losartan