Interpretation and optimization of urinary and plasma NGAL as biomarkers in a porcine model of ischemia-reperfusion acute kidney injury

Acute kidney injury (AKI) is a frequent and severe syndrome defined by impaired renal function commonly associated with tubular epithelial injury. Neutrophil Gelatinase-Associated Lipocalin (NGAL) is a sensitive early biomarker of AKI, but the optimal measurement matrix (urine or plasma) remains debated, particularly in the setting of oliguria or anuria. The aim of this study was to compare the diagnostic performance of plasma versus urinary NGAL for intrinsic AKI in a porcine ischemia–reperfusion model with anuria and a 10-hour observation period, including the impact of surgery-induced inflammation on the two matrices. AKI was induced by bilateral renal artery cross-clamping. NGAL concentrations were quantified by ELISA in plasma and urine at multiple timepoints in two groups: AKI and Sham. Interleukin-6 (IL-6) and C-reactive protein (CRP) were assessed as markers of systemic inflammation. A linear mixed-effects model was used to assess statistical differences, while Fisher’s exact test and Spearman’s rank correlation were used for other analyses. Urinary NGAL demonstrated higher sensitivity than plasma NGAL for the detection of AKI in this experimental model. Adjustment of urinary NGAL-to-creatinine improved both sensitivity and specificity compared with other evaluated biomarkers. Plasma IL-6 and CRP levels increased in both groups, reflecting surgery-induced inflammation. However, only IL-6 levels significantly differentiated the AKI group from the Sham group. Likewise, plasma NGAL did not differ significantly between groups. In conclusion, urinary NGAL, particularly when normalized to creatinine, outperformed plasma NGAL the diagnosis of intrinsic AKI in this experimental setting, in which systemic inflammation reduces the diagnostic relevance of plasma biomarkers.