The clinical course of renal diseases depends on the type of renal disorder, genetic factors, environmental influences, and the severity of renal fibrosis. Proteinuria is the abnormal amount of... Show moreThe clinical course of renal diseases depends on the type of renal disorder, genetic factors, environmental influences, and the severity of renal fibrosis. Proteinuria is the abnormal amount of proteins present in the urine. Proteinuria is an independent risk factor for development of renal insufficiency, in which glomerulosclerosis can be seen in biopsies. Experimental models described in this thesis show that different genetic factors are linked to proteinuria and glomerulosclerosis. Furthermore, bone marrow and kidney transplantations between proteinuria-prone and proteinuria-resistant rats, revealed that both renal and bone marrow-derived cells contribute to development of proteinuria or convey resistance to its development. The mechanism of development of segmental glomerulosclerosis is not completely known. We investigated glomerular morphology in hyperfiltration-mediated proteinuria before glomerulosclerosis was present. Segmental glomerulosclerosis started with segmental podocyte damage with loss of podoplanin protein. Focal and segmental glomerulosclerosis is a human renal disease with a wide range of glomerular morphology, a large range of clinical presentations, progression rates, and chances of developing recurrent FGSG after transplantation. A new histological classification was proposed in 2004 in hopes of separating new disease subentities. We found that in most cases FSGS recurred as the same variant, supporting the new classification. The results in this thesis may increase the insights in the development of proteinuria and glomerulosclerosis, hoping to result in earlier recognition of renal disease, better definition of patients and separation of distinct disease entities. This may lead to better and more disease-specific treatment options. Show less
