WCN26-6374 INTERNATIONAL PROSPECTIVE MULTICENTRE INITIATIVE ON POSTOPERATIVE ACUTE KIDNEY INJURY IN CHILDREN AFTER NONCARDIAC SURGERY ( POAKIDS)

nephropathy mouse model, and diabetic nephropathy mouse model and its potential as a therapeutic target.Here, we investigated the roles of ApoM in cisplatin-induced nephropathy using a mouse model and potential novel downstream mechanisms modulated by ApoM.Methods: ApoM-knockout mice (KO) and wild-type (WT) mice on a C57BL/6 background received a single intraperitoneal injection of cisplatin (15 or 30 mg/kg).Blood samples were collected, and the mice were euthanized at 96 hours after infection, and their kidneys were harvested for analysis.Plasma creatinine (Cr) was measured.Renal histology was assessed by Periodic acid-Schiff (PAS) staining, and tubular injury area was quantified.Expression of apoptosis-related proteins (Bax, Bcl-2, Bcl-xl, cleaved caspase-3), survival signaling molecules (Akt, SIRT1), mitochondolial biogenesis markers (PGC-1, and TFAM, ND-1) were analyzed by Western blot.HK-2 cells were used for mechanistic insight, and siRNA mediated knockdown of ApoM was performed.Results: Cr was elevated in KO mice at both doses: 1.60 mg/dL vs. 2.87 mg/dL (p < 0.01) at 15 mg/kg, and 1.64 mg/dL vs. 5.67 mg/dL (p < 0.01) at 30 mg/kg.Renal histology showed no difference in tubular injury area between WT and KO mice at a dose of 15 mg/kg (13.5%[KO] vs 7.8% [WT], p = 0.23), but KO mice showed severe damage at 30mg/kg (78.2% [KO] vs 9.1% [WT], p = 0.02).Western blot revealed increased cleaved caspase-3 and Bax/Bcl-2 ratios with reduced Akt phosphorylation and SIRT1 expression in KO mice, suggesting enhanced apoptosis.Mitochondrial regulators (PGC-1, TFAM) were also down-regulated in KO mice, indicating decreased mitochondrial function and metabolic downregulation in injured tubular cells.In HK-2 cells, knockdown of ApoM recapitulated the increased susceptibility to cisplatin.Conclusion: ApoM knockout mice exhibited worsened renal function in blood tests and histology, along with progressive mitochondrial dysfunction and apoptosis.These findings highlighted ApoM as a critical modulator of renal protection against cisplatin injury and suggested the therapeutic potential of targeting the ApoM/S1P axis in acute kidney injury induced by cisplatin as well as chronic kidney diseases.I have no potential conflict of interest to disclose.I did not use generative AI and AI-assisted technologies in the writing process.