Serum Cystatin C as an Early Predictive Biomarker for Acute Kidney Injury (AKI) in Neonates: A PRISMA-DTA Systematic Review.

BACKGROUND: Acute kidney injury (AKI) affects 12-40% of critically ill newborns and significantly increases mortality risk. Diagnosis currently relies on serum creatinine (sCr), which rises only after substantial renal damage, so early biomarkers are needed in this vulnerable population. Serum cystatin C (sCysC) is a candidate because it is produced at a constant rate by all nucleated cells. AIM: The study aimed to investigate the diagnostic performance of sCysC for early detection of neonatal AKI. METHODS: This systematic review followed the PRISMA-DTA guidelines and is registered with PROSPERO (CRD420261302574). We searched four databases for studies measuring sCysC in neonates (0-28 days) with validated assays and creatinine-based AKI definitions as the reference standard. Studies were categorized by sampling timing as concurrent diagnostic or early predictive, and appraised with QUADAS-2 and QUIPS, respectively. RESULTS: Thirteen studies were included. In the early predictive group, sCysC was elevated at scheduled timepoints preceding creatinine-defined AKI, with AUC values of 0.670-1.000. The concurrent diagnostic studies reported sensitivities of 84.8-88.5%, specificities of 61.8-75.0%, and AUC values of 0.844-0.849. Reported cut-offs ranged from 0.60 to 2.87 mg/L, with one sepsis-associated AKI study reporting 9.4 mg/L. CONCLUSIONS: sCysC is a promising adjunctive biomarker whose earlier elevation may support earlier recognition of neonatal AKI. Standardized assays and validated population-specific thresholds are required before routine clinical use.