The Department of Biomedicine

BBB seminar: Börje Haraldsson

Current understanding of kidney disease opens new therapeutic avenues

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Börje Haraldsson
Department of Clinical and Molecular Medicine (Nephrology), Sahlgrenska
Academy, Gothenburg University, Sweden

Kidney diseases are concealed disorders without any specific signs or symptoms. The discomforts of the patient are mainly fatigue, reduced ability to focus, and loss of energy. If not suspected and tested for, these signs of kidney disease are easily dismissed as depression or dyspeptic problems and the diagnosis is often delayed. In most countries, there is approximately one individual per thousand that is living with dialysis or with a kidney transplant. The cost for society is quite extensive and is close to €100,000 per person per year in hemodialysis. Thus, the costs for nephrology are actually higher than those for cardiology.

Most kidney diseases are glomerular in origin. Thus, the damage is due to inflammation (glomerulonephritis) or sclerosis of the glomerular capillaries secondary to diabetes and/or hypertension. For decades, the treatment options have been appallingly scarce; in most cases there is no specific treatment, or the therapy is slow with common and serious side effects. Lately, however, new therapeutic alternatives have emerged due to the molecular revolution started by the discovery of nephrin by Karl Tryggvason’s group at the Karolinska Institute.

During this talk, I will present our current understanding of the glomerular barrier and its components. Some of the most recent molecular targets that have been presented during the last year will be discussed. Perhaps even more interesting is the inter-cellular communication between podocytes, glomerular endothelial cells and mesangial cells that all are part of the glomerulus. Indeed, such cell-cell-communication was recently shown to be fundamental for the development of certain nephrotic syndromes such as focal segmental glomerulosclerosis (FSGS). Thus, an interesting transgenic mouse model was used that allows for cell-specific and conditional overexpression of human constituently active transforming growth factor (TGF) beta-1 receptor in podocytes. Such activation induces endothelin-1 production in the podocytes, signaling to the endothelium where it induces mitochondrial oxidative stress, apoptosis and reduced stimulating feedback to the podocytes. If the endothelium is protected, the kidney disease will be prevented or cured.

I will close by describing what we have learned about the kidney and its glomeruli during the last years, and will provide some insight into the fascinating possibilities that may provide new therapies for patients with kidney disease.

Chairperson: Helge Wiig, Department of Biomedicine