Early brief treatment with losartan plus mycophenolate mofetil provides lasting renoprotection in a renal ablation model.
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.
Fujihara
Clarice Kazue
CK
Department of Clinical Medicine, University of São Paulo School of Medicine, Brazil.
Vieira
Jose Mauro
JM
Sena
Claudia Ramos
CR
Ventura
Bianca Helena
BH
Malheiros
Denise Maria
DM
Zatz
Roberto
R
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
D047228:Angiotensin II Type 1 Receptor Blockers; D000893:Anti-Inflammatory Agents; D020011:Protective Agents; D009173:Mycophenolic Acid; D019808:Losartan