Complement activation in renal microangiopathies

Abstract

In this thesis, the involvement of the complement system was studied in various diseases that affect the microvasculature of the kidney. We focused on the clinicopathologic significance of complement deposits along the renal microvasculature of patients with thrombotic microangiopathy, a disorder that is characterized by severe endothelial injury and microvascular thrombosis; IgA nephropathy and IgA vasculitis with nephritis, auto-immune disorders that can cause microvascular injury in adults and children; transplant glomerulopathy, an important cause of late graft dysfunction and renal allograft loss; preeclampsia, a leading cause of maternal and perinatal morbidity and mortality; and diabetic nephropathy, a microvascular complication of diabetes mellitus and a leading cause of end-stage renal disease. Special attention was paid to C4d, a cleavage product of C4 activation, which is commonly used as a biomarker for complement activation. Our data suggest that the complement system is involved in the pathogenesis of various renal microangiopathies and that complement activation along the microvasculature may contribute to disease progression in a subset of patients. Our findings may contribute to the development of improved diagnostic workup, new therapeutic strategies and patient-tailored therapy.