Advances in biomarker-based assessment of kidney injury in pediatric nephrotic syndrome: A narrative review

Pediatric nephrotic syndrome (NS) presents significant diagnostic and prognostic challenges in contemporary clinical practice. Despite advances in understanding disease mechanisms, substantial gaps persist in risk stratification frameworks, standardized diagnostic criteria for complex cases, and clinical implementation of novel biomarkers. The present review aimed to critically evaluate current and emerging diagnostic approaches for detecting early kidney injuries in pediatric nephrotic syndrome, examining developmental renal physiology, disease mechanisms, conventional marker limitations, novel biomarkers and multi-marker strategies to provide evidence-based recommendations for improving early detection and long-term outcomes in affected children. The review summarizes current evidence on the clinical relevance of novel biomarkers of kidney injury, including neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid–binding protein (L-FABP), N-acetyl-β-D-glucosaminidase, cystatin C, interleukin-18, and osteopontin. These biomarkers reflect different pathophysiological mechanisms such as tubular injury, inflammation, ischemia, oxidative stress, fibrosis and are able to detect subclinical renal damage before a measurable decline in glomerular filtration rate occurs. Particular attention is given to KIM-1, NGAL, and L-FABP as early indicators of tubular injury, as well as to osteopontin as a marker associated with chronic inflammation and renal fibrotic remodeling. Available data indicate that the combined use of several biomarkers improves early detection, risk stratification and monitoring of disease course in children with nephrotic syndrome.