Nephrotic syndrome in children

Nephrotic syndrome is an important chronic disease in children, characterized by minimal change disease in the majority. Research on pathogenesis has emphasized the importance of T lymphocyte dysregulation and vascular permeability factors that might alter podocyte function and permselectivity. While mutations in genes that encode important podocyte proteins have also been identified, a hypothesis unifying available evidence on pathogenesis is yet to be proposed. Patients with nephrotic syndrome are at risk for life threatening infections and thromboembolic episodes. Long-term effects of persistent hyperlipidaemia and prolonged steroid therapy are increasingly recognized. Remission of proteinuria following corticosteroid therapy has greater prognostic value, in relation to long-term outcome, than the precise renal histology. Prospective studies show that prolonged duration of therapy for the initial episode results in sustained remission and reduced frequency of relapses. Treatment with levamisole, cyclophosphamide, cyclosporine and mycophenolate mofetil is beneficial in a variable proportion of patients with frequent relapses or steroid dependence. The management of steroid-resistant nephrotic syndrome is difficult; most patients failing to achieve remission show progressive renal damage. Calcineurin inhibitors (cyclosporine, tacrolimus) are capable of inducing remission in a significant proportion of patients, but at risk of nephrotoxicity. Reduction of proteinuria is also possible, in children, using angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers. Prospective trials are necessary to identify effective and safe therapies for patients with frequent relapses, steroid dependence and resistance.