Renal Biomarkers of Injury as Early Predictors of COVID-19 Associated Acute Kidney Injury: A Prospective Observational Trial (BRICOAKI Study)

Background and aims: Acute kidney injury (AKI) is a common and serious complication among critically ill COVID-19 patients.Early identification of patients at risk is challenging because serum creatinine rises late in the course of renal injury.Unlike prior COVID-19 AKI studies that measured serum neutrophil gelatinase-associated lipocalin (sNGAL) or Cystatin-C at a single time point, this study evaluates their serial trajectories and quantifies biomarker-creatinine lead-time in a critically ill intensive care unit (ICU) cohort.Patients and methods: This prospective observational study involved 65 adults with moderate to severe COVID-19 in the ICU.Serum biomarkers [NGAL, cystatin-C, interleukin (IL)-6, kidney injury molecule (KIM)-1, tissue inhibitor of metalloproteinases (TIMP)-2, creatinine] and urinary Klotho (uKlotho) were measured on days 0, 1, 2, 3, 5, 7, and 10.Acute kidney injury was defined per kidney disease: Improving global outcomes (KDIGO) criteria.Receiver operating characteristic (ROC) analysis and lead-time estimation evaluated predictive performance.Results: Acute kidney injury occurred in 47/65 (72.3%) patients; of them, 36/47 (76.6%) progressed to KDIGO stages 2-3, and 5 (10.6%) required renal replacement therapy (RRT).Among the biomarkers studied, sNGAL demonstrated the highest discrimination for KDIGO-defined AKI [area under curve (AUC): 0.71-0.79]and increased approximately 1 day before creatinine-based AKI diagnosis.Serum cystatin-C (sCystatin-C) showed moderate predictive value (AUC: 0.63-0.70)with a median lead time of approximately 1-2 days.Serum KIM-1 (sKIM-1) demonstrated only borderline variation across severity groups, while uKlotho did not show significant discriminatory performance.Although TIMP-2 and IL-6 were significantly elevated with increasing disease severity, their overall discriminative performance for AKI was lower compared with NGAL and cystatin-C. Conclusion:In critically ill COVID-19 patients, serial sNGAL and sCystatin-C demonstrated modest but consistent discrimination for KDIGOdefined AKI and showed a tendency to rise 1-2 days prior to creatinine-based diagnosis.In contrast, sKIM-1, serum TIMP-2, uKlotho, and serum IL-6 exhibited limited discriminatory performance for early AKI detection.