Early dynamic changes of KIM-1, IL-18, and NGAL and the preventive effects of recombinant alkaline phosphatase in a rat model of sepsis-associated acute kidney injury

Abstract Background and aim Sepsis-associated acute kidney injury (SA-AKI) is a frequent and severe complication of sepsis. Conventional renal markers such as serum creatinine and blood urea nitrogen (BUN) often reflect established injury rather than early pathophysiological changes. This study aimed to characterize the early dynamic behavior of kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), and neutrophil gelatinase-associated lipocalin (NGAL) in a rat model of SA-AKI, and to evaluate the preventive effects of recombinant alkaline phosphatase (recAP). Materials and methods SA-AKI was induced by lipopolysaccharide (LPS) administration in Sprague–Dawley rats. Serum creatinine, BUN, KIM-1, IL-18, and NGAL were measured at 2, 4, and 8 h after LPS exposure. Renal histopathology was assessed using hematoxylin–eosin staining. Renal tissue expression of KIM-1, IL-18, NGAL, Toll-like receptor-4 (TLR4), nuclear factor-κB-p65 (NF-κB-p65), and phosphorylated NF-κB-p65 was evaluated by Western blot analysis. recAP was administered prophylactically at three dose levels prior to LPS challenge. Results LPS administration resulted in significant renal dysfunction and histological injury. Serum BUN increased as early as 2 h, while creatinine elevation became more pronounced at later time points. KIM-1, IL-18, and NGAL showed early and dynamic increases following LPS exposure, with distinct temporal patterns. recAP pretreatment attenuated biomarker elevations, improved renal histopathology, and suppressed activation of TLR4/ NF-κB pathway in a dose-dependent manner. Conclusion KIM-1, IL-18, and NGAL exhibit early dynamic changes during SA-AKI that complement traditional renal markers rather than replace them. recAP exerts a preventive, dose-dependent renoprotective effect, likely mediated through modulation of inflammatory signaling pathways. These findings provide integrative preclinical evidence supporting biomarker-guided evaluation of early renal injury and preventive strategies in sepsis.