A study conducted by the Renal Pathophysiology Research Group at Vall d’Hebron Research Institute, in collaboration with the Pediatric Nephrology Department of Vall d'Hebron University Hospital. The study was awarded at the 56th edition of the European Society for Pediatric Nephrology (ESPN) Congress, held in Valencia this past September. The ESPN brings together clinical professionals and researchers working in the field of pediatric nephrology across Europe, with the aim of spreading knowledge and improving the treatment of children with kidney diseases.

The awarded communication, titled “Patients with Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis with Different Disease Progression Have a Differential Expression Profile of Urinary miRNAs”, was presented by Julieta Torchia, a predoctoral researcher from the group. The work is part of a study aimed at identifying the mechanisms of progression of Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis (HFHNC), a rare disease affecting the kidneys. It is also aimed at understanding why patients show different phenotypes despite having the same mutation (p. G20D, the most common in Spain and France) in the Claudin 19 gene.

HFHNC is an ultra-rare hereditary disease caused by mutations in the genes that code for Claudin 19 and Claudin 16. It is characterized by the renal loss of calcium and magnesium, and can lead to end-stage renal failure, requiring a transplant within a few months of life in the most severe cases. Congenital ocular defects that limit vision to varying degrees are also characteristic. Currently, there is no specific treatment for this condition.

The considerable phenotypic variability among patients, even among those presenting the p. G20D mutation in homozygosity and within families, suggests the presence of other genetic, epigenetic, and/or environmental factors that could be modulating the severity and progression of the disease. For this reason, the research team has isolated extracellular vesicles from the urine of HFHNC patients to compare the differential expression profiles of miRNAs between patients and healthy controls, and among patients with different disease progression. Some of these miRNAs are small RNA molecules that regulate gene expression and could be clinically relevant as non-invasive urinary biomarkers, and at the same time, serve as new therapeutic targets.

“This study has allowed us to partially understand the molecular mechanisms of disease progression and define possible targets and therapeutic solutions through artificial intelligence algorithms,” explains Julieta Torchia. She adds: “Receiving this recognition at an international congress is important because it helps increase the visibility of our work and offers the possibility of establishing collaborations with other research groups to respond to this rare disease.”

The team emphasizes that “the results of this research not only represent a major breakthrough for patients affected by HFHNC and their families, but they could also be useful for other renal diseases with a similar clinical progression, thus expanding the population that could benefit from this research.”

This project has been made possible thanks to the participation of the Association for Information and Research on Familial Hypomagnesemia (HIPOFAM).