Nephrotic Syndrome: State of the Art

Abstract

This article overviews the pathogenesis and management of idiopathic nephrotic syndrome, a common childhood glomerulopathy. While initial evidence supported an imbalance of T helper responses in patients with nephrotic syndrome, recent studies suggest alterations in both innate and adaptive immune responses, including evidence for impaired T regulatory function. The central role of the podocyte in causing proteinuria is confirmed by the observation of mutations in key podocyte proteins in steroid-resistant nephrotic syndrome and experimental evidence of altered podocyte signaling and cytoskeletal organization, which might be corrected by medications. The outcome and management of idiopathic nephrotic syndrome in children are determined by the response to corticosteroids and the frequency of relapses. While patients with steroid-sensitive nephrotic syndrome have a favorable long-term outcome, almost half of them relapse frequently and are at risk of adverse effects of corticosteroids. Various non-corticosteroid immunosuppressive agents are used to prolong disease remission, but require careful monitoring for potential adverse effects. While calcineurin inhibitors are the choice of therapy for patients with steroid-resistant nephrotic syndrome, long-term management of disease is challenging due to variable response to immunosuppression, therapy-related adverse effects, and high rates of disease progression to end-stage renal disease. Information from recent randomized clinical trials has helped to clarify and improve the standard of care for childhood nephrotic syndrome and underscore the need for well-designed collaborative studies.