Early identification of sepsis-induced acute kidney injury utilizing NGAL, Cystatin C, urine output, and serum creatinine in a porcine (Sus scrofa) model of septic shock: A comparative study of fluid and vasopressor strategies

<ns5:p> Background Sepsis-associated acute kidney injury (SA-AKI) is a common complication of septic shock and is associated with prolonged ICU stay and increased mortality. Early detection of renal injury remains challenging because conventional markers such as serum creatinine and urine output often reflect delayed functional changes. Structural biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C, have emerged as promising indicators for the earlier detection of kidney injury. The aim of the study was to compare early structural biomarkers (NGAL and cystatin C) with conventional functional markers (serum creatinine and urine output) in a porcine model of septic shock, and to evaluate their temporal patterns under three different fluid and/or vasopressor resuscitation strategies. Methods A randomized controlled experimental study was conducted using six <ns5:italic>Sus scrofa</ns5:italic> pigs subjected to standardized septic shock induction. Animals were allocated into three groups: fluid resuscitation with Ringer’s lactate (30 mL/kg), fluid combined with early norepinephrine infusion, and early norepinephrine with maintenance fluids. Plasma NGAL, cystatin C, serum creatinine, and ultrasonographically assessed urine dynamics were measured sequentially. Hemodynamic parameters were continuously monitored. Data were analyzed using repeated-measures and nonparametric tests with a significance level of p < 0.05. Results NGAL and cystatin C demonstrated earlier temporal changes compared with serum creatinine across all groups. Ringer’s lactate only and Ringer’s lactate-norepinephrine groups showed declining biomarker trends after intervention, whereas the early norepinephrine group exhibited delayed increases. Serum creatinine remained stable during the observation period. Intergroup differences were not statistically significant. Conclusion Structural biomarkers exhibited earlier dynamic changes than serum creatinine in this porcine septic shock model. Although statistically non-significant, distinct biomarker patterns were observed among resuscitation strategies, suggesting potential value of integrating sensitive renal biomarkers with individualized hemodynamic management for early detection of SA-AKI. </ns5:p>