Kidney Int. 2026 Sep 26:S0085-2538(26)00819-7. doi: 10.1016/j.kint.2026.06.054. Online ahead of print.
ABSTRACT
Idiopathic nephrotic syndrome (INS) is the most common chronic glomerular disease in children. Corticosteroids remain first-line therapy, and the initial response, differentiating steroid-sensitive (SSNS) from steroid-resistant (SRNS) forms, is the strongest prognostic factor. While most childhood-onset INS results from an incompletely defined dysregulation of the immune system, up to one-third of children with initial SRNS have a monogenic etiology. SSNS typically follows a relapsing-remitting course, with one-half of the patients having frequent relapses or steroid-dependence (FRNS/SDNS). Although earlier studies suggested that most SSNS patients achieve sustained remission by puberty, approximately one-fourth experience at least one relapse in adulthood. Key predictors of persistent relapsing disease include FRNS/SDNS in childhood and the need for second-line immunosuppression. The disease may evolve into secondary steroid-resistance in <10% patients with SSNS. Kidney failure and death remain uncommon. In contrast, SRNS is associated with higher risks of therapy-and disease-related complications, including growth impairment, obesity, hypertension and cardiovascular risk, osteoporosis, cataracts, calcineurin inhibitor-induced nephrotoxicity, acute kidney injury and progressive chronic kidney disease. The risk of kidney failure is three- to fourfold higher in patients with monogenic and/or multidrug-resistant SRNS. This review synthesizes current evidence on the long-term outcomes of childhood-onset INS, highlights risk stratification across clinical phenotypes, genetic diagnosis and treatment response, and challenges during transition to adult care.
PMID:42800615 | DOI:10.1016/j.kint.2026.06.054