Neutrophil gelatinase-associated lipocalin and kidney injury Molecule-1 as potential biomarkers of the transition from rhabdomyolysis-induced acute kidney injury to chronic kidney disease.

The pathogenesis involved in the progression of rhabdomyolysis-induced Acute Kidney Injury (AKI) to Chronic Kidney Disease (CKD) remains unclear. Moreover, the assessment of AKI-to-CKD progression should include kidney injury biomarkers, since functional parameters present limitations. This study evaluated the potential of Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Kidney Injury Molecule-1 (KIM-1) as biomarkers associated with maladaptive renal repair after rhabdomyolysis-induced AKI. Wistar rats received intramuscular injections of saline or glycerol (50%), 8 mL/kg, forming Control and Glycerol groups. Throughout the 45-day study, the blood pressure was evaluated, and the renal function was assessed. After euthanasia, renal histopathology, Masson's trichrome staining, and immunolabeling for transforming growth factor-β1 (TGF-β1), collagen I, and fibronectin were performed. Inflammatory infiltration and capillarity were also evaluated. Oxidative stress markers and antioxidant enzyme activities were analyzed. Despite the recovery of renal function 45 days after AKI, Glycerol rats showed increased tubulointerstitial injury (p = 0,0006) and higher Masson's trichrome (p < 0.0001), TGF-β1 (p = 0.0007), collagen I (p = 0.0002), and fibronectin (p = 0.0002) staining. Renal NGAL (p = 0.0456) and KIM-1 (p = 0.0075) levels were elevated, while only serum (p = 0.0029) and urine (p = 0.0335) NGAL were increased, after 45 days of AKI. These findings were associated with capillary rarefaction (p = 0.0014), increased macrophage (p < 0.0001) and lymphocyte (p = 0.0004) infiltration, reduced of catalase (p = 0.0028) and glutathione peroxidase (p < 0.0001), and elevated oxidative stress markers in Glycerol rats. In conclusion, our data evidenced incomplete renal recovery after rhabdomyolysis-induced AKI and highlighted NGAL as a biomarker of persistent injury, while acute-phase urinary KIM-1 showed predictive potential for maladaptive renal repair.