The pathogenetic basis of idiopathic
nephrotic syndrome, a common childhood glomerulopathy, is being explored. While initial evidence supported an imbalance of T helper responses, 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. The outcome and management of idiopathic
nephrotic syndrome in children is 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. Although various non-
corticosteroid immunosuppressive agents are used to prolong disease remission, careful monitoring is required for the potential adverse effects.
Calcineurin inhibitors have emerged as the choice of
therapy in patients with
steroid resistant nephrotic syndrome. However, the management of this form of the disease is particularly challenging because of the variable response to immunosuppression, therapy-related significant adverse effects and high rates of
disease progression to
end stage renal disease. Patients with both
corticosteroid sensitive and resistant forms of the disease are at risk of complications of disease, and require close monitoring and repeated counseling.