Hereditary Congenital and Infantile Nephrotic Syndrome in Children: Strategy of Management with New Possibilities for Genetic Diagnosis and Therapy

Abstract

Due to the worldwide genetic research, the fundamental information was obtained regarding the pathogenesis of the hormone-resistant congenital and infantile nephrotic syndrome in children. The mutations in the genes encoding the main components of the basement membrane of the kidney glomeruli, structural and functional podocyte proteins are responsible for the development of the congenital and infantile nephrotic syndrome with the typical histologic pattern of the diffuse mesangial sclerosis or focal segmental glomerulosclerosis. In accordance with the evidence-based international strategy, the clinical phenotyping combined with the targeted genetic analysis is the diagnosis standard for the hereditary nephrotic syndrome in children that are recommended to perform the genetic analysis prior to start of the steroid therapy and prior to the kidney biopsy. The early genetic diagnosis assures the personalized approach to the choice of the therapies considering the genotype and phenotype specifics of the congenital or infantile nephrotic syndrome in the particular child. The up-to-date strategy for the management of such children provides the carrying out of the conservative therapy and early transplantation of the related kidney when reaching 10-15 kg body weight (in this case, the kidneys are removed and transplanted during the same surgery), or the bilateral nephrectomy simultaneously or one stepped, then the second kidney and peritoneal dialysis, then kidney transplantation for the children reached 10-15 kg body weight. According to ESPN / ERA-EDTA register (2016), the 5-year survival rate of the children with the congenital nephrotic syndrome caused by NPHS1 gene mutation is 91% after kidney transplantation, 89% after allograft. The solutions for the pressing challenge of the domestic pediatrics are as the following: introduce the international strategy into the practice of the children management with the congenital and infantile nephrotic syndrome with the new possibilities of the genetic diagnosis and therapy replacing the kidney function; enhance the kidney transplantation and its availability; carry out the epidemiological studies of the hereditary nephrotic syndrome.