STUDY OF THE PATHOPHYSIOLOGICAL MECHANISMS INVOLVED IN ACUTE KIDNEY INJURY CAUSED BY HEMOLITC ANEMIA

Hemolytic anemia-induced acute kidney injury (HA-AKI) is a clinical manifestation of acute renal dysfunction resulting from the release of inflammatory mediators during erythrocyte lysis—an event common to various hemolytic diseases. The pathophysiology of HA-AKI involves structural and functional changes linked to the toxicity of the heme group and other hemolysis products, leading to inflammation, tubulointerstitial injury, and proteinuria. The literature indicates that iron metabolism in renal fibroblasts and the formation of reactive oxygen species (ROS) contribute to the renal dysfunction and injury observed in hemolytic anemia. Objective: To understand the potential mediating role of hemolytic anemia products in the development of the renal injury and dysfunction observed in HA-AKI. Methods: We used male C57Bl6 mice (8-week-old) to develop the hemolytic anemia-induced acute kidney injury through a single intraperitoneal injection of phenylhydrazine (PHZ, 125 mg/kg). Two groups were established: 1) CONT group, non-anemic animals injected with vehicle (n=6); and 2) PHZ group, animals with anemia induced by PHZ (n=9) (CEUA-UFMG#103/2026). Analyses were performed four days after anemia induction: hematological parameters (such as red blood cell count, size, and staining) and renal injury parameters. Results: Our preliminary results showed that the PHZ group exhibited a hemoglobin level of 6 g/dL, confirming the anemic state in animals treated with the drug, while the CONT group showed an Hb level of 12 g/dL. Regarding renal injury markers, the PHZ group displayed significantly increased proteinuria when compared with the CONT group. Structural evaluation of the renal parenchyma revealed tubule-interstitial injury and intense hemosiderin deposition in the kidneys of the PHZ group. Conclusion: Our preliminary results showed that PZH successfully induces hemolytic anemia and increased hemolytic factors, which in turn, induce tubulointerstitial injury and proteinuria in mice. This model would be helpful to study the pathophysiological mechanism underlying the HA-AKI.