Congenital Nephrotic Syndrome

Abstract

Children with congenital nephrotic syndrome (CNS) present within the first 3 months of life. Primary CNS is typically caused by mutations in genes encoding for components of the glomerular filtration barrier. The classical form is the Finnish type of CNS (CNF, NPHS1) caused by mutations in NPHS1 (nephrin) gene, and it typically causes heavy proteinuria in the newborn period. Pathogenic variants in other genes namely NPHS2 (podocin), WT1 (Wilms tumor suppressor 1), LAMB2 (laminin β2), and PLCE1 (phospholipase C epsilon 1, NPHS3) can also cause CNS, which have more variable clinical manifestations including a wider age range at disease onset. Mutations in these five genes together account for >80% of CNS patients. Besides genetic causes, CNS can be secondary to other diseases like congenital infections or immune disorders. The diagnosis of CNS and its underlying etiology is based on several features including clinical presentation, family history, laboratory findings, genetic testing, and histology. While medical management is possible for certain forms of secondary CNS, kidney transplantation is the only curative treatment for most patients with genetic CNS. In unstable patients with refractory nephrotic states, bilateral nephrectomy and dialysis followed by transplantation may be considered after they attain body weights of 7-10 kg. In stable patients, nephrectomy is not needed, and renal replacement therapy is commenced when they reach end-stage kidney disease (ESKD). Transplantation should be performed when the patient is no longer nephrotic. The outcome of transplantation in CNS patients is satisfactory, and comparable to other pediatric kidney patients.