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Cyclo (His-Pro) is an effective treatment for the AKI-to-CKD Transition

ABSTRACT: Acute kidney injury (AKI) with maladaptive repair induces transition to chronic kidney disease (CKD) through inflammation, oxidative stress, and inappropriate homeostatic responses, including senescence and apoptosis. Here, we demonstrate that administration of cyclo Histidine-Proline (Cyclo His-Pro, CHP) protects against kidney injury and progression to CKD. Exogenous CHP pre-treatment preserved kidney function and produced significant reduction in tubular injury, apoptosis, and inflammatory cell infiltration in an ischemia-reperfusion injury (IRI) model. Compared with 5/6 nephrectomy (Nx) control rats, kidney function was protected and fibrosis was attenuated in CHP-treated 5/6 Nx rats. CHP also improved kidney injury in a unilateral ureteral obstruction (UUO) model with both prophylactic and therapeutic treatment regimens. To translate our observations to the human setting, we evaluated the relationship between endogenous CHP levels and CKD progression. As kidney function deteriorated, plasma CHP concentration increased, whereas tissue expression of Nrf2 displayed a negative relationship with CKD progression, suggesting that plasma CHP levels increase as a compensatory process to enhance the Nrf2 pathway activity. The data presented here support the efficacy of exogenous CHP treatment in preventing AKI-to-CKD transition potentially through Nrf2 pathway activation. Results: Cyclo (His-Pro) is an effective treatment for the AKI-to-CKD Transition

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE159228 | GEO | 2025/02/08

REPOSITORIES: GEO

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