Genetics and pathogenesis of progressive glomerulosclerosis

Abstract

Glomerulosclerosis is a general term describing the process of scarring of the glomeruli, the functional units in the kidney that filter urine from the blood. This severe, irreversible complication can occur secondary to various already established systemic or local diseases. However, not all patients with renal diseases show progression to end stage renal disease (ESRD). Thus renal patients can be subdivided into progressors and non-progressors based on clinical parameters1. Why patients with renal diseases become progressors or non-progressors is unclear, and better insight into the pathogenesis of glomerulosclerosis may improve our understanding of the process towards progression. However, the pathogenesis of glomerulosclerosis is complex and still poorly understood, although genetic factors probably play a role, given the considerable variation among individuals in both the risk of developing glomerulosclerosis and the rate of progression. Therefore, the first aim of the work described in this thesis was to identify genes involved in the progression and repair of glomerulosclerosis, using an animal model that allows a clear distinction between progression and repair after renal injury. The second aim was to gain better insight into the pathogenesis of glomerulosclerosis by investigating the expression and activity of fibrosis-related molecules in an animal model and in patients with renal diseases.