Discovery of a genetic factor that quadruples the risk of end-stage renal failure!

Press release - UCLouvain Brussels research

An international team led by Prof. Olivier Devuyst (UCLouvain and Cliniques universitaires Saint-Luc) and Dr Eric Olinger (University of Zurich, Newcastle University, Cliniques universitaires Saint-Luc) has identified, for the first time, an intermediate-effect mutation in a gene (UMOD) that plays an important role in the kidney. This mutation, present in about one in 1,000 people of European descent, increases by a factor of four to five the risk of end-stage renal failure, which requires costly treatment (dialysis or transplantation).

Chronic kidney disease (CKD), which has a strong genetic predisposition, affects 10% of the world’s population and an equivalent percentage of the Belgian population. It most often leads to end-stage renal failure requiring dialysis or transplantation. Deciphering the genetic architecture of CKD is crucial to identifying new therapeutic targets for preventing or delaying the progression of CKD.

Up to now, as Prof. Devuyst has explained, two types of genetic mutations (or variants) were observed: either very rare mutations with a severe effect on the kidney, which are involved in rare diseases; or frequent variants that are present in everyone but have a barely perceptible effect on the kidney. A third type of mutation, with an intermediate effect, had long been predicted, to better account for the inherited component of CKD. The team led by Dr Eric Olinger and Prof. Devuyst succeeded in identifying this type of intermediate-effect mutation in the UMOD gene that is known to play a role in kidney disease.

The mutation, detected in about one in 1,000 individuals, causes an intermediate biological effect in the kidney that increases the risk of end-stage CKD by a factor of four in combined cohorts of more than 600,000 individuals. In Belgium, this could affect some 10,000 people.

This discovery would not have been possible without access to large databases, in particular the UK Biobank, which collects genetic and clinical data on 500,000 healthy individuals. This database, combined with others, enabled the researchers to validate their hypotheses. These genetic advances are important from the point of view of precision medicine: knowledge of such genetic factors will eventually make it possible to specify the risk of certain diseases and thus to adapt treatment.

This discovery, which provides a better understanding of the genetic architecture of CKD, has been published in the prestigious American journal Proceedings of the National Academy of Sciences (PNAS), which highlights the originality and value of the UCLouvain researchers’ multidisciplinary approach and its applicability to other genes and diseases.

Olivier Devuyst is a professor at the UCLouvain Institute of Experimental and Clinical Research (IREC) and coordinator of the Institut des Maladies rares (Institute for Rare Diseases) at Cliniques universitaires Saint-Luc. Eric Olinger is a post-doctoral fellow at the University of Zurich and Newcastle University and is continuing his training at the Human Genetics Centre of Cliniques universitaires Saint-Luc.