Dr. Gerard Cantero-Recasens, junior principal investigator of the Renal Pathophysiology group at Vall d'Hebron Institute of Research (VHIR), has received one of the ten annual grants awarded by the Mizutani Foundation for Glycoscience in Japan. The grant will fund a line of research in Dent's disease, a rare genetic disorder that affects the kidneys and progresses to chronic kidney disease and renal failure. The Renal Pathophysiology group, led by Dr. Anna Meseguer in collaboration with Dr. Gema Ariceta, head of the Pediatric Nephrology Department at the Vall d’Hebron University Hospital, have been working in this pathology for years with the support of the Dent’s disease association (ASDENT).

The project led by Dr. Cantero will receive $45,000 (equivalent to €41,790) to advance our understanding of the biological basis of Dent's disease, specifically the role of the ClC-5 protein. This protein is mutated in patients with this pathology, and this causes alterations in the renal tubules that can lead to kidney failure. The researchers are interested in finding out the relationship between mutations in ClC-5 and kidney function problems.

The role of ClC-5 and the impact on kidney tubular function

The kidneys are essential organs for filtering the blood and regulating the excretion of wastes and toxins. Blood is filtered in structures called glomeruli, which are attached to tubules that are responsible for recovering proteins that have escaped from glomerular filtrate. To achieve this, the cells of the proximal tubule have external receptors capable of binding to the proteins circulating in the filtrate and introducing them into the interior (endocytosis).

When ClC-5 does not function, the number of endocytosis receptors and other markers is reduced, and the cells cannot carry out their function properly. "We want to learn how the loss of ClC-5 translates into a loss of epithelial markers and dedifferentiation of the cells and, therefore, dysfunction of the proximal tubules of the kidney", says Dr. Cantero.

The researchers believe that ClC-5 creates an acidic environment in the Golgi apparatus, one of the organelles of cells, which is necessary for proper glycosylation of epithelial markers and receptors. Glycosylation is the process by which a carbohydrate is added to the molecule, which serves as a marker for the receptors to reach the cell membrane. Therefore, malfunction of ClC-5 would affect glycosylation and ultimately the function of tubule cells.

"We hope that our results will set the basis for new therapies and help to develop prognostic biomarkers for Dent's disease and even for other complex kidney diseases", remarks Dr. Cantero.

In recent months, Dr. Cantero has been on a research stay at the Osaka International Cancer Institute in Japan thanks to a grant from the European Molecular Biology Organization (EMBO) to learn new techniques related to glycosylation, which are key to research in Dent's disease.