Molecular Markers with Impact on Kidney Graft Survival and Glomerulopathies Progression

The progression of chronic glomerulopathy and graft rejection is affected by a number of proinflammatory cytokines, whose role in the pathogenesis of damage is poorly understood. The aim of this dissertation was to identify reliable risk markers of renal dysfunction progression and thereby contribute to a more effective patient treatment. Human native kidney biopsies with histologically confirmed diagnosis of glomerulopathy or kidney graft biopsies were analysed. Intrarenal gene expressions were measured by RT-qPCR. Single nucleotide polymorphisms were detected by methods based on PCR-RFLP. Immunohistochemical staining was used to identify and quantify the mononuclear cell infiltration. Gene expression of TGF-β1, HGF, BMP7, MCP-1, RANTES and mononuclear cell infiltration were associated with poor renal function and proteinuria at the time of IgA nephropathy diagnosis. Progression of IgA nephropathy during the 2-year follow-up was shown to be dependent on the degree of chronic vasculopathy and TGF-1 expression in the kidney. Patients with graft dysfunction and enhanced intrarenal expression of TGF-1, MCP-1 had significantly shorter graft survival. Higher mRNA expression of IL-10, TGF- 1, IL-6, MCP-1, RANTES and TNF- was observed in patients with graft dysfunction presented at the time of biopsy...