Proteinuria is an independent risk factor for the progression of kidney injury, cardiovascular morbidity, and overall mortality. In this thesis, the pathways leading to proteinuria are explored by... Show moreProteinuria is an independent risk factor for the progression of kidney injury, cardiovascular morbidity, and overall mortality. In this thesis, the pathways leading to proteinuria are explored by revisiting elements previously considered essential, investigating known pathways, and identifying new players in the field of proteinuria. First, a zebrafish embryo model for developing new therapeutic options for the rare but devastating disease of nephropathic cystinosis is presented. The studies presented in thesis also investigate loss of heparan sulphate glycosaminoglycans in a zebrafish embryo model and in multiple osteochondroma patients. These studies show that loss of heparan sulphate glycosaminoglycans does not always lead to proteinuria. Next, dynamin is described as a promising potential therapeutic target for treating proteinuria. The final study introduces transmembrane protein 14A as an essential factor in maintaining glomerular filtration barrier function. Overall, these studies contribute to elucidating the pathways to proteinuria in the hope to keep advancing the field towards targeted treatment of proteinuria for the benefit of our patients. Show less
__Bones can break, muscles can atrophy, glands can loaf, even the brain can go to sleep, without immediately endangering our survival, but when the kidneys fail to manufacture the proper kind of... Show more__Bones can break, muscles can atrophy, glands can loaf, even the brain can go to sleep, without immediately endangering our survival, but when the kidneys fail to manufacture the proper kind of blood neither bone, muscle, gland nor brain can carry on__. This quote from Homer Smith's book 'From Fish to Philosopher' indicates the importance of the kidney for the maintenance of the harmonious composition of body fluids __ a function the kidney performs in a way that joins efficacy with elegance. Some of these processes are lined out in this thesis. The first chapter gives an introduction to kidney development, anatomy, and function, as well as a description of malfunction of the kidney, focusing on the development of proteinuria and failure of kidney transplants. The subsequent chapters describe studies that have been performed to investigate the biological mechanism that underly the development of proteinuria and long-term renal transplant failure. Show less
