Fenotypická charakteristika a patofyziologie dědičných nefropatií v dětském věku(Geneticky podmíněný nefrotický syndrom a atypický hemolyticko-uremický syndrom u českých dětí)

• Main Author: Malina, Michal
• Other Authors: Seeman, Tomáš
• Format: Doctoral Thesis
• Language: Czech
• Published: 2012
• Online Access: http://www.nusl.cz/ntk/nusl-327891

Hereditary nephropathies are a heterogeneous group of disorders comprising of diseases of the kidney per se and syndrome diseases where kidney pathology is predominantly manifested. We have focused on two important glomerulopathies manifesting predominantly in childhood - nephrotic syndrome with genetic background and atypical hemolytic uremic syndrome. In the first part of the work we present five years of observation of cohort of children with steroid resistant nephrotic syndrome. We have identified 32 cases from which 7 carried genetic mutations causing nephrotic syndrome (22%). Most striking finding in our group was high rate of responsiveness to cyclosporine in our cohort regardless of genotype of the patient. Even patients bearing mutation in NPHS2 gene showed partial responsiveness to cyclosporine (43%) Second part of the work focused on very rare disease of complement cascade - atypical hemolytic uremic syndrome. In retrospective study of 10 patients with familial presentation we found high rate of patients (n=4, 40%) with MCP mutations. This is in contrast to published cohorts where prevalence of these mutations is around 6-10%. All four our mutations were functionally tested and were proven as functionally relevant. All carriers showed decrease of MCP/CD46 molecules on cell surfaces. This...