Thromboembolic prophylaxis in childhood idiopathic nephrotic syndrome. From pathophysiology to clinical management.

Thromboembolic complications remain among the most serious complications of childhood idiopathic nephrotic syndrome (INS). Although their incidence is considerably lower than in adults, venous thromboembolism continues to cause substantial morbidity and occasional mortality, including pulmonary embolism, cerebral venous sinus thrombosis, and extensive deep venous thrombosis. Preventive management remains controversial because most affected children may not develop thrombosis, whereas pharmacological prophylaxis exposes many low-risk patients to potential overtreatment. Current recommendations are largely based on retrospective studies, expert opinions, and extrapolation from adult nephrotic syndrome, while prospective pediatric evidence remains scarce. This review examines the contemporary understanding of thrombogenesis in childhood INS, emphasizing that hypercoagulability extends beyond urinary antithrombin loss to involve hepatic overproduction of procoagulant factors, impaired fibrinolysis, platelet activation, endothelial dysfunction, and hemoconcentration. We also discuss the possibility that historical thrombotic risk may have been amplified by prolonged corticosteroid exposure and consider whether the widespread adoption of steroid-sparing immunosuppressive therapies and earlier relapse detection may have modified the epidemiology of thromboembolism in the modern therapeutic era. Current preventive strategies-including no routine prophylaxis, biomarker-guided individualized approaches, aspirin, and prophylactic low-molecular-weight heparin (LMWH)-are critically reviewed. We argue that increasingly complex biomarker-based algorithms have not demonstrated clear clinical superiority over simple, pragmatic decision-making. Severe hypoalbuminemia provides a pragmatic surrogate of nephrotic severity and may therefore help identify children in whom the overall prothrombotic state is likely to be substantial. We are not proposing albumin <20 g/L as a validated predictor of thrombosis. We are proposing it as a pragmatic clinical trigger for considering prophylaxis in a disease in which no validated predictive model currently exists. We propose a pragmatic risk-stratified approach in which routine pharmacological prophylaxis is unnecessary for early biochemical relapses with minimal clinical manifestations but should be strongly considered in children and adolescents with clinically significant active nephrotic syndrome associated with severe hypoalbuminemia (approximately <20 g/L), provided no major contraindications exist. Where feasible, LMWH appears to be the most appropriate prophylactic agent. Until prospective pediatric studies better define thrombotic risk and validate prediction models, practical consistency based on clinically meaningful risk thresholds may provide a more rational framework than theoretical precision for thromboprophylaxis in childhood INS.