2026-04-27
Kidney diseases: discovery of a “conductor” that worsens disease progression
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Chronic kidney disease (CKD) affects more than 10% of the global population, representing nearly 850 million people. It is characterized by a progressive and irreversible decline in kidney function, which may ultimately require dialysis or transplantation. While its risk factors—such as diabetes, hypertension, obesity, and inflammation—are well established, one particularly concerning feature remains: even when the initial cause is treated, the disease almost always continues to progress. This self-sustaining nature, long poorly understood, represents a major challenge in clinical management.
In this context, two research teams from the Necker-Enfants Malades Institute (Inserm/CNRS/Université Paris Cité), led by Dr. Marco Pontoglio and Dr. Fabiola Terzi, sought to identify the mechanisms responsible for this relentless progression. Their work focused on HNF1B, a protein known for its key role in kidney embryonic development and in regulating numerous genes.
A multi-model experimental approach
The researchers combined human data with mouse models to investigate the consequences of reduced HNF1B activity in the adult kidney. They relied on advanced gene expression analysis techniques, as well as the study of more than 900 kidney biopsies covering various stages and causes of chronic kidney disease. This integrated approach aimed to link early molecular changes with functional alterations.
A molecular vicious cycle
The researchers also identified a specific gene expression signature regulated by HNF1B, which is altered very early in disease models—sometimes even before visible lesions appear. This alteration is associated with impaired tissue repair.
Moreover, the study highlights a self-perpetuating mechanism: pathological factors such as inflammation or the presence of albumin in urine reduce HNF1B activity. “Our results reveal the existence of a true vicious cycle that explains the self-sustaining nature of kidney diseases: reduced HNF1B activity promotes kidney disease, and in turn, kidney disease progressively suppresses HNF1B activity, further aggravating kidney damage,” explained Dr. Marco Pontoglio in an Inserm press release.
Analysis of human biopsies confirms the robustness of this mechanism: the molecular signature of HNF1B loss of function is consistently observed, with intensity correlating with disease severity. “This study establishes HNF1B as a true guardian of kidney function. Its loss of activity, for the first time, links rare genetic kidney diseases and common forms of chronic kidney disease through a single mechanism,” emphasized Dr. Fabiola Terzi.
Therapeutic perspectives
By identifying a unifying mechanism that explains continuous disease progression, these findings open up promising therapeutic avenues. “Finding a way to restore HNF1B activity could help slow down, or even modify, the course of chronic kidney disease,” concluded Dr. Fabiola Terzi.
Beyond the kidney, this discovery also invites further investigation into whether similar mechanisms of loss of cellular identity and harmful feedback loops may exist in other chronic diseases, potentially opening new directions in translational medicine.
Read next: sFas: a new warning signal in kidney disease?
About the Author – Elodie Vaz
Health journalist, CFPJ graduate (2023).
Élodie explores the marks diseases leave on bodies and, more broadly, on human life. A registered nurse since 2010, she spent twelve years at patients’ bedsides before exchanging her stethoscope for a notebook. She now investigates the links between environment and health, convinced that the vitality of life cannot
Source(s) :
HNF1B intègre des signaux dans une boucle d’avance qui favorise la progression de la maladie rénale ;
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