Emerging pharmacotherapies for the treatment of childhood nephrotic syndrome

Childhood nephrotic syndrome (NS) is a relatively rare condition but an important cause of morbidity. It is classified based on histopathology and response to corticosteroid therapy.

Children with steroid-sensitive disease have a favorable long-term prognosis with maintenance of normal kidney function. However, nearly half of these patients have persistent disease activity requiring chronic corticosteroid therapy or exposure to second-line immunosuppressive agents. The identification of anti-nephrin antibodies in many patients with steroid-sensitive disease suggests immunotherapy to reduce pathogenic antibody formation may represent a qualitative advance in treatment. Children with steroid-resistant disease are likely to have focal segmental glomerulosclerosis (FSGS). There are no approved treatments for this condition. FSGS is a heterogeneous entity, and improvements in care will likely depend on molecular classification of subtypes based on the underlying disease mechanism. This approach will enable selection of treatments that match the cause of NS in each child for precision medicine therapy.

Children with NS today benefit from therapeutic options not previously available, but clinical decisions still rely on steroid responsiveness at disease onset. Continued advancement in treating NS requires collaboration between basic scientists and nephrologists and the organization of a clinical trial framework to evaluate novel therapies.