Acute Kidney Injury in Childhood Nephrotic Syndrome: From Hemodynamic Vulnerability and Tubular Stress Toward Biomarker-Guided Management

Acute kidney injury (AKI) is a clinically important, mechanistically heterogeneous complication of childhood nephrotic syndrome. Similar increases in serum creatinine may reflect reduced effective arterial volume, extracellular volume expansion with pressure-associated dysfunction, acute tubular stress or injury, infection or sepsis, drug toxicity or acute interstitial nephritis, vascular thrombosis, or underlying glomerular disease. These mechanisms often coexist or evolve, so edema and creatinine alone cannot direct therapy. This focused narrative review links the nephrotic substrate and precipitating exposures to predominant or mixed AKI phenotypes, multimodal assessment, and phenotype-guided management. Serum creatinine, urine output, and cystatin C are considered alongside urinary neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and the cellular stress product of tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 [TIMP-2]·[IGFBP7]. These biomarkers may help distinguish functional filtration loss from tubular stress or damage, but nephrotic-syndrome-specific validation and evidence of therapeutic utility remain limited. Management should integrate serial assessment of perfusion, congestion, fluid balance, urine findings, drug exposures, infection, and vascular or intrinsic kidney disease. Biomarkers are therefore adjuncts, not an established basis for management.