Introduction: Snakebite-induced acute kidney injury (SAKI), affecting about 10-30% of the envenomed patients, is the least studied AKI in which involvement of immunoinflammatory and pro-fibrogenic mediators has rarely been reported.

Aim: In the present study, we aim to evaluate the pathophysiological importance of immune cell and alterations in their population in SAKI patients and venom-induced experimental murine model of SAKI.

Methods: Hematological profiling and immunophenotyping in SAKI patients and venom-treated animal group was carried out and compared with that of normal healthy controls for both sets. Renal histopathological and immunohistochemical analysis in murine model was also carried out. Neutrophilic leukocytosis associated with lymphocytopenia and mild-to-moderate thrombocytopenia was noted in SAKI patients and murine model compared to control group.

Results: Immunophenotypic characterization of peripheral lymphocyte shows significantly elevated regulatory T cells and cytotoxic T-cell associated with significant reduced CD4+/CD8+ ratio in both human patients and murine model of SAKI. Murine splenic and thymic lymphocyte shows similar polarization toward regulatory and cytotoxic T cells. Further analysis revealed a significant increase of splenic regulatory (CD25+Foxp3+IL-10+) helper and cytotoxic T cells. Renal immunohistochemical analysis showed a remarkable increase in collagen deposition and tissue infiltration by TCR-α+ and Foxp3+ cells into the renal interstitial space along with higher expression of TGFβ1 and CTGF.

Conclusion: Taken together, the results of the present study clearly indicated codominance of acute inflammation and T-cell polarization towards regulatory subset and pro-fibrotic cytokines in both human and murine SAKI.