Renal disorders About themeThe mission of the renal disorders theme is to deliver excellent, efficient and innovative clinical care to our patients at the Radboudumc and beyond, and to be leading in the field of kidney disease research. The primary aim of the renal disorders theme is to understand the molecular mechanisms, physiology and pathogenesis of glomerular diseases and tubular transport disorders, including acquired and inherited forms of kidney diseases. To achieve this aim, we will increase knowledge of the molecular and immunological basis of glomerular and tubular disorders; develop biomarkers for optimal prediction of disease prognosis; and apply strategies for preventing and improving renal replacement therapy. The research projects are carried out at genetic, molecular, cellular and integrative levels, as well as on human subjects.
- We will increase knowledge of the molecular and immunological basis of glomerular and tubular disorders and of graft performance.
- We will combine genetic and functional cutting-edge methodology to diagnose and identify novel renal diseases.
- We will identify novel therapeutic targets for renal disorders and kidney transplant survival.
- We aim to develop biomarkers for optimal diagnosis, prevention and prognosis of renal diseases, kidney injury and transplant survival.
- We aim to optimize treatment strategies for patients with renal diseases, focusing on patient-tailored treatment.
- We will apply strategies for preventing and improving renal replacement therapy.
Lines of research
Glomerular diseasesThe 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.
Renal replacement therapy
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.
The research lines within the renal disorders theme focus on both clinical and experimental research topics concerning renal transplantation. Various aspects of immune regulation are studied, such as the generation and characterization of tolerogenic dendritic cells, and the role of chemokines and heparan sulfate. As part of the BioKid consortium, researchers from the renal disorders theme aim to develop living membranes for an intradialytic biological kidney support device, which will be capable of effective clearance of toxins ex vivo, improving haemodialysis.
Tubular disordersIn 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.