Related Experiment Video
Updated: Apr 18, 2026
08:50
5/6th Nephrectomy in Combination with High Salt Diet and Nitric Oxide Synthase Inhibition to Induce Chronic Kidney Disease in the Lewis Rat
Published on: July 3, 2013
24.5K
HNF1B integrates signals in a feed-forward loop driving kidney disease progression
Pierre Isnard1,2, Munevver Parla Makinistoglu1, Michel Leibovici1
1Université Paris Cité, INSERM U1151, CNRS UMR8253, Institut Necker Enfants Malades, Paris, France.
Science (New York, N.Y.)
|April 16, 2026
Summary
Chronic kidney disease (CKD) progression involves self-sustaining mechanisms. We identified the transcription factor HNF1B as a key driver, linking its loss to CKD severity and unifying rare and common kidney disorders.
Area of Science:
- Nephrology
- Molecular Biology
- Genetics
Background:
- Chronic kidney disease (CKD) affects over 10% of the global population.
- CKD progression can persist after initial insult resolution, indicating poorly understood self-sustaining mechanisms.
- Renal epithelial identity is regulated by transcription factors, including HNF1B.
Purpose of the Study:
- To identify the molecular circuitry driving self-sustaining CKD progression.
- To investigate the role of HNF1B in kidney disease.
- To link HNF1B dysfunction to both rare and common forms of CKD.
Main Methods:
- Investigated HNF1B's role in adult kidney epithelial cells.
- Analyzed epigenetic regulation of HNF1B in CKD models.
- Correlated HNF1B activity with CKD severity in a patient cohort (n=900).
Main Results:
- HNF1B loss disrupts renal epithelial differentiation, quiescence, and induces replication stress, triggering CKD.
- CKD epigenetically suppresses HNF1B activity, creating a self-amplifying disease cycle.
- Lower HNF1B activity significantly correlated with increased CKD severity in patients.
Conclusions:
- HNF1B is a central regulator of renal epithelial homeostasis and a key driver of CKD.
- The HNF1B-centered circuitry explains self-sustaining CKD progression.
- This mechanism unifies rare Mendelian and common complex kidney diseases, identifying HNF1B loss as a critical factor.
Related Concept Videos
01:28Diabetic Nephropathy
2
Definition Diabetic nephropathy is a chronic kidney complication that results from prolonged hyperglycemia.Prevalence It is the most common cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD) worldwide, affecting up to half of individuals with diabetes.Pathophysiology • Sustained hyperglycemia triggers multiple hemodynamic and metabolic changes in the kidney. • Early in the disease, increased renal blood flow and glomerular hyperfiltration...
2
01:25Chronic Kidney Disease I: Introduction
1.3K
Chronic Kidney Disease (CKD) arises when the kidneys progressively lose their ability to function, ultimately leading to end-stage renal disease. At this advanced stage, the kidneys can no longer filter waste or maintain essential body functions, requiring renal replacement therapy (RRT) through dialysis or a kidney transplant for survival.Early-stage chronic kidney disease and detection challengesIn CKD's early stages, symptoms often remain absent because healthy nephrons compensate for...
1.3K
01:10Nephrons
9.9K
The kidneys are intricate organs with millions of working units known as nephrons. Each nephron features two major structures: the renal corpuscle, which facilitates blood plasma filtration, and the renal tubule, which handles the glomerular filtrate. Blood supply is directly linked to the nephrons. The renal corpuscle consists of the glomerulus, a capillary network, and the Bowman's capsule, a double-walled epithelial structure that encases the glomerulus. The filtering of blood plasma...
9.9K
01:24Chronic Kidney Disease II: Clinical Manifestations
1.1K
Chronic Kidney Disease (CKD) progressively impairs multiple body systems due to the accumulation of uremic toxins, which disrupt cellular functions across various organs.Neurologic symptomsNeurologic symptoms often arise early in CKD, as uremic toxin buildup drives changes in cognitive and motor functions. Patients frequently experience fatigue, headache, confusion, difficulty concentrating, and, in severe cases, seizures. Peripheral neuropathy commonly manifests as burning sensations in the...
1.1K
01:28Chronic Kidney Disease III: Interprofessional Care
652
Chronic kidney disease (CKD) requires collaborative and comprehensive management. CKD progresses through stages and can lead to end-stage kidney disease (ESKD) if untreated. Interprofessional collaboration and patient education are crucial, enabling patients to manage their health and improve their quality of life.Diagnostic approach for chronic kidney diseaseThe diagnosis of CKD primarily focuses on the glomerular filtration rate (GFR), which assesses kidney function by measuring how well...
652
01:29Acute Kidney Injury II: Pathophysiology
2.1K
Acute kidney injury (AKI) causes are categorized into three primary categories based on the location of the injury: prerenal, intrarenal (or intrinsic), and postrenal causes. This classification guides clinical management and illustrates how different pathways can impair kidney function.Etiology and Pathophysiology of Acute Kidney Injury1. Prerenal causesEtiology: Prerenal Acute Kidney Injury, the most common type, occurs when reduced blood flow to the kidneys decreases filtration capacity...
2.1K