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Institute of Physiology

Mechanisms of inherited kidney disorders Prof. Dr. med. Olivier Devuyst

Regulation of body fluid homeostasis is of vital importance for all terrestrial organisms. In most mammals, the maintenance of the hydration status and normal plasma electrolytes levels critically depends on the appropriate handling of water and ions by the kidneys. This essential function involves specific transport systems operating in the epithelial cells lining kidney tubules. In the past two decades, our understanding of the transport mechanisms across biological membranes has substantially improved with the molecular identification and structural characterization of key proteins (channels, transporters, or their regulators) that are expressed in the nephron. The discovery of these molecules, initiated by classical biochemical approaches, has benefited from the molecular genetics analysis of rare genetic diseases. The analysis of such diseases has provided essential informations about the mechanisms of water and solute handling by the nephron. In turn, these insights improved the diagnosis, follow-up and treatment of renal diseases and associated conditions such as dehydration, electrolyte disorders, hypertension, growth retardation, nephrolithiasis, and progressive renal failure.

Understanding the nature and clinical relevance of fluid and ion transport across biological membranes has driven our research since the early 1990’s. Based on a multi-disciplinary approach including studies on patients, human and mouse genetics, and analysis of mouse and cellular models, we have investigated the transport mechanisms operating in various segments of the kidney, their regulation and ontogeny, and the pathophysiology of inherited renal disorders including tubulopathies and polycystic kidney disease. Insights obtained through these investigations are relevant for common conditions such as blood pressure regulation, kidney stones, progression of renal failure, and cardiovascular complications of renal diseases. The knowledge of transport mechanisms also led us to work on the molecular basis of water and solute transport across the peritoneal membrane, with the aim of improving peritoneal dialysis, a therapeutic modality for patients with end-stage renal disease. Over the years, our studies benefited from fruitful international collaborations, leading us to initiate and participate in several European networks. These collaborations allow us to develop our projects using genome, transcriptome and proteome analyses; genome-wide association studies; conditional KO and randomly mutagenised mice; in translation with studies of human tubular disorders collected at the European level.

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July 2023

New publication by Olivier Devuyst et al. in Nature Communications and in UZH News:

Lysosomal cystine export regulates mTORC1 signaling to guide kidney epithelial cell fate specialization



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The University Research Priority Program (URPP) ITINERARE (2021 - 2032) fosters excellent translational research on rare diseases at the University of Zurich (UZH) and beyond. Furthermore, ITINERARE addresses the ethical, legal, social, and educational aspects associated with rare diseases. The URPP is headed up by immunologist Janine Reichenbach, physiologist Olivier Devuyst and metabolic diseases expert Matthias Baumgartner.  

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AcceleRare, a Swiss answer to the challenges of rare diseases

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