Genetic basis of steroid resistant nephrotic syndrome and implications for therapy

Steroid-Resistant Nephrotic Syndrome (SRNS) is an uncommon cause of chronic renal disease thatoccurs principally in children and young adults. No specific treatment is available. Patients with SRNShave an unfavourable prognosis and usually develop end stage renal disease within 10 years from theonset. Familial forms have been reported, indicating that SRNS has genetic causes. The pathogenesis of SRNS is poorly defined. The available data indicate that podocyte, a specializedcell type that forms part of the glomerular filtration barrier, plays a central role in maintaining renalfunction. Genetic studies have identified podocyte proteins, whose alteration is responsible for thedevelopment of SRNS. Despite the recent advances in the comprehension of SRNS pathogenesis, however the underlying genetic alteration/s remains unknown in the majority of patients. General aim of the present project is to characterize the genetic causes of SRNS and possibly identifynew genes whose alterations may lead to the development of SRNS. By implementing ourInternational Registry of SRNS we will have access to biological samples and clinical data from highnumber of patients and families. We will search for mutations and characterize the function of proteinsencoded by newly identified SRNS-associated genes and study the functional consequences of themutations. In patients that will be genotyped we will perform correlations between genetic data andclinical outcome. This will help in tailoring treatment according to genetic background, which mayprevent unnecessary exposure of patients with podocyte alterations to toxic effects of steroid therapyand may pave the way to hypothesis-driven treatments.