Publication dans Cell Death & Disease

If you suffer from diabetes, your kidneys are at risk!


If you suffer from diabetes, your kidneys are at risk. Diabetes attacks these organs by creating a lack of oxygen. A new therapeutic strategy, based on the findings of an international consortium co-directed by Professor François Jouret (CHU de Liège), suggests acclimatizing the kidneys to this lack of oxygen in order to prevent diabetic kidney disease.

 

Diabetes is responsible for a veritable pandemic: it affects ~550 million people worldwide, including ~60 million in Europe and ~800,000 in Belgium (i.e. 7% of the Belgian population). Diabetes attacks various organs, such as the eyes, nerves and kidneys. In Belgium, around 1 million people suffer from kidney disease, the main cause of which is diabetes. However, the mechanisms of this diabetes-induced kidney disease (DKD) remain poorly understood, hampering the development of new, more effective and better-targeted drugs.

A recent collaborative study by researchers from the Universities of Liège (Prof. Fr. Jouret) and Kiel in Germany (Prof. Fr. Theilig) investigated the role of hypoxia in the development of DRK. Hypoxia is caused by a lack of oxygen. It is implicated in various diseases, notably via the "VHL" (Von Hippel-Lindau) protein, which is an indicator of proper cellular oxygenation.

By inducing diabetes in mice whose kidneys do not express the VHL gene, the researchers found that these kidneys behave "as if acclimatized to hypoxia", ultimately protecting them against diabetes. In particular, the loss of albumin in urine was lower in VHL-deficient mice than in control animals. This albuminuria is a well-known prognostic marker for MRD: the higher it is, the more severe the disease. The researchers' hypothesis is that artificially creating hypoxia at a very early stage of diabetes would slow the development of MRD. Professor Fr. Jouret comments: "Our results open up new prospects for the understanding, prevention and treatment of the kidney disease frequently observed in diabetic patients. Indeed, new drugs modulating hypoxia are already available on the market: they could represent an innovative strategy in the management of diabetic patients."

This study, published in the journal Cell Death & Disease, represents a major advance in research into diabetes, a very common disease with unacceptable morbidity and mortality. Every year, diabetes is the direct cause of 1.5 million deaths worldwide, ~50% of which occur before the age of 70.

Reference

Targeted deletion of von-Hippel-Lindau in the proximal tubule conditions the kidney against early diabetic kidney disease.

Kunke M, Knöfler H, Dahlke E, Zanon Rodriguez L, Böttner M, Larionov A, Saudenova M, Ohrenschall GM, Westermann M, Porubsky S, Bernardes JP, Häsler R, Magnin JL, Koepsell H, Jouret F, Theilig F.
 
Cell Death Dis. 2023 Aug 26;14(8):562.

 

Contact

Prof. François JOURET

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