Genetic architecture of kidney diseases


The research of Prof. Olivier Devuyst (IREC) aims to improve the efficiency of dialysis through the study of genetic renal diseases. His work has been rewarded twice in recent weeks.

Without kidneys, the fundamental balance of the body is no longer assured. Organs too often forgotten, they nevertheless provide a vital role of balance within our body. It’s a discreet but essential role: as producers of urine, kidneys allow the elimination of waste from our diet, metabolism and certain drugs. But that's not all: ‘Beyond the simple elimination of waste in the urine, the kidney reabsorbs and controls the composition of our internal environment’, Prof. Devuyst explains.‘It regulates blood pressure and produces a series of vital hormones that influence, for example, bone quality and red blood cell count. When it no longer works, the whole organism is in danger.

The professor, a nephrologist for 25 years at UCLouvain’s Saint-Luc University Hospital, has just been awarded the 2019 Award for Outstanding Basic Science Contributions to Nephrology by the European Society of Nephrology, Dialysis and Transplantation (ERA-EDTA). The distinction, the most important in Europe, crowns all of his work on genetic renal diseases and the mechanisms of dialysis. Earlier this year, Prof. Devuyst received the D.G. Oreopoulos Memorial Award at the congress of the Canadian Society of Nephrology in Montreal.

The dual recognition is a reflection of today’s kidney failure crisis. The number of such patients has increased dramatically in the last decade; one in ten is affected today. ‘When I returned from the United States in 1996, I had the chance to take over the nephrology laboratory founded by Prof. Charles van Ypersele. Thanks to excellent support and collaboration with UCLouvain's clinical department, we have been able to conduct original research on genetic renal diseases and dialysis, which are linked by fundamental biological mechanisms.’

Genetic renal diseases

Genetic diseases in the broad sense are a common cause of kidney failure. Identifying them has improved considerably over the last decade, thanks to better clinical recognition and the advent of reliable and less expensive genetic tests. Prof. Devuyst's work focuses on many of these diseases, which affect different kidney segments. An example is polycystic kidney disease, one of the most common genetic diseases, which results in the presence of innumerable cysts in the kidneys, generating multiple complications including progressive renal failure in adults. This disease affects nearly 10,000 people in Belgium. ‘Our experimental work, coupled with the specialised care of these patients, has led to significant advances including clinical studies and the recent introduction of the first targeted treatment of the disease – which patients can benefit from under certain conditions.’ Prof. Devuyst's team is working on these genetic diseases using a multidisciplinary approach, based on experimental models and clinical studies. ‘This research on rare diseases allows us to better understand the fundamental mechanisms of kidney function, and to identify genetic factors operating at the level of the general population. Indeed, the same genes can be involved in rare and severe diseases as well as in subtle changes in renal function. In this field of so-called “rare” diseases, our participation in several European programmes has made real progress, resulting in better knowledge of the mechanisms involved and identifying new therapeutic targets. Clinically, our genetic renal diseases centre is the only French-speaking Belgian centre that is part of the European Rare Kidney Disease Reference Network (ERKNET).

Peritoneal dialysis

When renal failure occurs at a very advanced stage, the patient must initiate renal replacement therapy, via dialysis or transplantation. Transplantation is often the best option but is unfortunately limited by the lack of donors. Patients must therefore often go through a dialysis stage. Prof. Devuyst's team has been working for a long time on peritoneal dialysis, a method applied at home that has the advantage of preserving the patient's autonomy and using a naturally occurring membrane in humans. The membrane, called the peritoneum, purifies the toxins and excess water from the patient's blood in a natural cavity in the abdomen, which has been previously filled with a sterile solution (dialysate). ‘Compared to hospital dialysis,’ Prof. Devuyst says, ‘which is generally limited to three times four hours a week and therefore needs to be quite intense, peritoneal dialysis allows the patient to self-dialyse at home, several times a day or at night, in a gentler way. Our work aims to better understand the transport mechanisms operating at the level of the peritoneal membrane. We have developed new methods for modelling and studying peritoneal dialysis, with a particular interest in the major role played by water channels – aquaporins. Our goal is to develop intervention strategies aimed at improving the effectiveness of dialysis, or at least limiting its complications.

Marie Dumas

A glance at Olivier Devuyst's bio

Prof. Olivier Devuyst is a specialist in genetic kidney diseases at Saint-Luc University Hospital, where he is clinical head and a professor in the Faculty of Medicine’s Nephrology Centre. Since 2010, he has headed the Mechanisms of Inherited Kidney Disorders (MIKADO) Laboratory at the University of Zurich (UZH); he teaches there and at the federal institute of technology, ETHZ Zurich.

Prof. Devuyst graduated from UCLouvain in Brussels Woluwe and trained at the Technion Institute (Haifa, Israel) and Johns Hopkins Medical School (Baltimore, USA). He is the author of more than 350 articles, has coordinated several EU-funded research networks and, in 2011, founded the European Working Group on Genetic Kidney Diseases (WGIKD ERA-EDTA). Since 2018, he has led the AcceleRare academic drug discovery project in Switzerland.

Since 2005 Prof. Devuyst has been a member of the Royal Belgian Academy of Medicine. He is the deputy editor in chief of Kidney International, Nephrology Dialysis Transplantation and the Orphanet Journal of Rare Diseases, and sits on the editorial board of the Clinical Journal of the American Society of Nephrology, Peritoneal Dialysis International, Frontiers in Physiology and Pflügers Archiv: European Journal of Physiology.

Published on June 25, 2019