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Published on: May 26, 2022
Early brief treatment with losartan plus mycophenolate mofetil provides lasting renoprotection in a renal ablation
Clarice Kazue Fujihara1, Jose Mauro Vieira, Claudia Ramos Sena
1Department of Clinical Medicine, University of São Paulo School of Medicine, Brazil.
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.
Conclusion:
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.
Insights
Early, temporary treatment with losartan (L) and mycophenolate mofetil (MMF) provided lasting kidney protection in rats after 5/6 ablation (Nx). Late treatment did not offer similar durable renoprotection.
Area of Science:
- Nephrology
- Pharmacology
- Pathophysiology
Background:
- Inflammatory processes and angiotensin II play key roles in early renal injury following 5/6 nephrectomy (Nx) in rats.
- Early, continuous treatment with mycophenolate mofetil (MMF) demonstrates renoprotective effects in this model.
- The study investigates the potential for lasting renoprotection with losartan (L) and/or MMF, even after treatment cessation.
Purpose of the Study:
- To determine if early losartan (L) or L+MMF treatment confers durable renoprotection in Nx rats after discontinuation.
- To assess if late-initiated L+MMF treatment provides lasting renoprotection in Nx rats.
Main Methods:
- Adult male Munich-Wistar rats underwent 5/6 Nx.
- Protocol 1 involved early treatment (day 1-30) with L or L+MMF.
- Protocol 2 involved late treatment (day 30-60) with L+MMF.
Main Results:
- Early treatment (Protocol 1) significantly attenuated hypertension, albuminuria, and renal injury by day 30.
- Renal protection persisted until day 120 in the early L+MMF group.
- Late treatment (Protocol 2) showed no significant difference compared to untreated Nx rats by day 120.
Conclusions:
- Temporary suppression of early hemodynamic and inflammatory factors in Nx rats leads to durable renoprotection.
- The timing of intervention is critical; early treatment is effective, while late treatment is not.
- These findings highlight the importance of early therapeutic strategies for long-term kidney protection.
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