Towards better management of chronic renal failure

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Researchers at Toulouse University Hospital, Inserm and Toulouse III - Paul Sabatier University have recently made a breakthrough in the understanding and treatment of chronic kidney disease, a pathology affecting millions of people worldwide. Published in Science Translational Medicine, this promising scientific breakthrough is based on the identification of the responsibility of an inflammatory protein in the serious complications of the disease, paving the way for a new therapeutic approach.

Vascular calcification: a serious complication of renal failure

Chronic renal failure affects 10% of the world’s adult population, and up to 30% of people over 70 in Europe.

One of the main complications of chronic renal failure is vascular calcification, a phenomenon in which minerals accumulate abnormally in the walls of blood vessels, causing them to stiffen and contributing to the development of serious cardiovascular disease, which is the main cause of death in these patients.

To date, the treatments available have limited effects and are unable to prevent or treat vascular calcification.

A new therapeutic approach linked to the identification of vascular calcification mechanisms

The research team carried out a large-scale proteomic analysis (a method of exploring the proteins present in a biological sample), combined with targeted ELISA analyses on plasma samples from renal failure and dialysis patients.(a cohort of 453 patients from the CKDomique cohort at Toulouse University Hospital, the Spanish Nefrona cohort, the Swedish KärlTx cohort at Karolinska Institutet, and the AURAR association in Reunion.

The ELISA test is an immunological test for the detection or assay of molecules in a biological sample.

This analysis identified the presence of an inflammatory protein called calprotectin, whose high level in patients’ blood was strongly associated with the development of cardiovascular complications and mortality in these patients.

More importantly, in vivo and in vitro studies have demonstrated the direct role of calprotectin in vascular calcification, paving the way for a new therapeutic approach. Indeed, this study highlights the therapeutic potential of paquinimod, a calprotectin inhibitor, as a promising drug candidate for limiting the development of vascular calcification.

"This European translational study offers promising prospects for improving the management of renal failure and dialysis patients by targeting vascular calcification. It represents a major advance in our understanding of the pathophysiology of vascular calcification in renal failure. In medical terms, these results pave the way for the potential use of paquinimod as a treatment, which could reduce morbidity and mortality due to preventable cardiovascular events in patients with renal failure. "Julie Klein, Renal Fibrosis Lab / Institut I2MC (UMR1297 Inserm / Université Toulouse III - Paul Sabatier) & Pr Stanislas Faguer, Département de Néphrologie et Transplantation d’Organes du CHU de Toulouse (directed by Pr Nassim Kamar) / Institut I2MC (UMR1297 Inserm / Université Toulouse III - Paul Sabatier)