The module
This course focuses on the Renal Disorders research theme (
www.rimls.nl/themes/renal- disorders/renal-disorders/) which delivers excellent, efficient and innovative clinical care to our patients in the Radboudumc and beyond, and aims to lead discovery in the field of kidney disease research in the world. To achieve this we aim (i) to increase knowledge on the molecular and immunological basis of glomerular and tubular disorders; (ii) to develop biomarkers for optimal prediction of disease prognosis; (iii) to apply strategies for the prevention and improvement of renal replacement therapy. Students will meet principal investigators and clinicians to be acquainted with a (molecular) understanding of the cause of renal disease.
The primary aim of the minor “Kidney in health and disease: the in’s & out’s of the theme Renal Disorder” is to understand the molecular mechanisms, physiology and pathogenesis of glomerular diseases and tubular transport disorders, including acquired and inherited forms of kidney diseases. Research projects are carried out on a genetic (gene defects, polymorphisms), molecular (channels, transporters and their regulation), cellular (glomerular and epithelial cells), integrative ([transgenic] mice, rats) level, as well as on human subjects and patients. The experimental research is fuelled by biomedical and clinical questions from population/man to molecule, and back.
The students will get acquainted with the design and results of fundamental and clinical research, with the ultimate goal to improve prevention, diagnosis, prognosis and cure of kidney disorders. Mechanistic insights from rare disorders are relevant for common disorders such as hypertension, kidney stones, cardiovascular disease, and progression of chronic kidney disease. Due to ageing of the population and the increased prevalence of diabetes, obesity and vascular disease, the number of patients with chronic kidney disease is growing. In this regard, the renal disorder theme will also address strategies to predict and retard the progression of chronic renal failure. Within the renal disorders theme, research lines are centered around four main topics that will be deliberated in detail namely:
Glomerular diseases
The glomerulus plays an essential role in the filtration of blood and the formation of urine. Knowledge of the structure and function of the glomerulus aids in understanding the clinical manifestations of glomerular diseases. Within the renal disorders theme, research on glomerular diseases is aimed at unraveling the molecular mechanisms underlying proteinuria, glomerular inflammation and sclerosis. Research lines focus on the role of heparan sulfate at the structure- functional level and the glomerular endothelial glycocalyx. The development of anti-chromatin autoantibodies and lupus nephritis is another key interest, and focuses on the effects of apoptotic blebs and apoptosis-induced chromatin modifications on dendritic cells. In addition, the role of podocyte injury in proteinuric glomerular diseases is studied, with special emphasis on the TRPC6 calcium channel and its role in focal segmental glomerulosclerosis.
Tubular disorders
In the kidney, prourine is concentrated along the nephron, where water and valuable electrolytes are reabsorbed to prevent excess losses via the urine. Over the last decades, a large number of patients were studied that suffer from hereditary defects leading to rare tubular disorders. These studies have led to the identification of a number of proteins and hormones that are involved in water and electrolyte homeostasis. Within the renal disorders theme, research lines focus on tubular transport of calcium, magnesium, sodium, iron and water. Studies mainly focus on the function and (hormonal) regulation of the transport proteins and channels that are responsible for the reabsorption of electrolytes and water in the kidney. In addition, the role of other organs, such as intestine, blood and bone, are studied, as they are essential to maintain homeostasis.
Renal replacement
In case of kidney failure, when kidney function is severely declined, treatment options are dialysis or renal transplantation. While dialysis is a life-saving treatment, it can only take over 10-15% of the work of a functioning kidney. A working kidney removes wastes from the body 24 hours a day and a single transplanted kidney can do 50-85% of the work of two functioning kidneys. The Radboud university medical center is one of the 8 Dutch centers transplantation centers, performing approximately 120 renal transplantations per year. Alternatively, we focus on the identification of biomarkers for nephrotoxic kidney injury. Also, the role of drug transporters in renal regeneration is investigated, with an emphasis on the role of stem cells in kidney tissue repair. When kidneys are damaged and renal function is lost, patients depend on haemodialysis to remove waste products from their blood. This procedure, however, causes an accumulation of certain waste products, leading to severe health complaints.
Ciliopathies
An increasing number of human genetic diseases are found to be caused by the disruption of proteins that localize to cilia; together these diseases are named ciliopathies. The cilium is of vital important form renal structure and function, which explains why in many of these ciliopathies the kidney is severely affected. Several cilia-related genes and proteins have been identified to have causal effects in polycystic kidney disease, nephronophthisis, Senior-Loken syndrome type 5, orofaciodigital syndrome type 1 and Bardet-Biedl syndrome. By combining next generation sequencing, systems biology approaches and biochemical analysis, researchers within the Renal Disorders theme aim to identify new key players in renal cilliopathies and to further elucidate the molecular mechanisms involved in these disease phenotypes.
The Renal disorders theme (
www.rimls.nl/themes/renal-disorders/renal-disorders/) consists of a dynamic group of fundamental and clinical researchers affiliated to the Research Institutes for Molecular Life Sciences and Health Sciences. Researchers from the theme form a strong and interdisciplinary team combining their expertise in Biochemistry, Genetics, Laboratory Medicine Nephrology, Pediatrics, Pathology, Pharmacology, Physiology, and Toxicology.