Download full-text PDF |
Source |
|---|
Publication Analysis
Top Keywords
Similar Publications
The evolving concepts of KS-WNK1 effect on NCC activity.
Am J Physiol Renal Physiol
February 2025
Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico.
The field of the with-no-lysine kinases (WNKs) regulation of the thiazide-sensitive NaCl cotransporter (NCC) began at the start of the century with the discovery that mutations in two members of the family, WNK1 and WNK4, resulted in a condition known as familial hyperkalemic hypertension (FHHt). Since FHHt is the mirror image of Gitelman's syndrome that is caused by inactivating mutations of the SLC12A3 gene encoding NCC, it was expected that WNKs modulated NCC activity and that the increased function of the cotransporter is the pathophysiological mechanism of FFHt. This turned out to be the case.
View Article and Find Full Text PDFFamilial Hyperkalemic Hypertension.
Compr Physiol
December 2024
Division of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University, Portland, Oregon, USA.
The rare disease Familial Hyperkalemic Hypertension (FHHt) is caused by mutations in the genes encoding Cullin 3 (CUL3), Kelch-Like 3 (KLHL3), and two members of the With-No-Lysine [K] (WNK) kinase family, WNK1 and WNK4. In the kidney, these mutations ultimately cause hyperactivation of NCC along the renal distal convoluted tubule. Hypertension results from increased NaCl retention, and hyperkalemia by impaired K secretion by downstream nephron segments.
View Article and Find Full Text PDFPrevalence of Hyperkalemia and Familial Hyperkalemic Hypertension in 5100 Patients Referred to a Tertiary Hypertension Unit.
Hypertension
November 2024
Division of Internal Medicine and Hypertension Unit, Department of Medical Sciences (M.T., J.B., F.V., F.R., P.M., S.M.), University of Torino, Italy.
Article Synopsis
- Hyperkalemia is a common electrolyte imbalance, impacting around 7.3% of patients with hypertension, often due to medications or chronic kidney disease.
- A small percentage (0.04%) of these patients had familial hyperkalemic hypertension (FHH), with higher prevalence in those with unexplained hyperkalemia.
- Hyperkalemia is linked to increased cardiovascular risks, emphasizing the need for early diagnosis and tailored treatment strategies for effective management.
Distal convoluted tubule-specific disruption of the COP9 signalosome but not its regulatory target cullin 3 causes tubular injury.
Am J Physiol Renal Physiol
October 2024
Division of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University, Portland, Oregon, United States.
Article Synopsis
- Familial hyperkalemic hypertension (FHHt), also known as Gordon syndrome, results from abnormal WNK4 accumulation that activates the NaCl cotransporter (NCC) in the kidneys, primarily affecting the distal convoluted tubule (DCT).
- Mutations in the cullin 3 (CUL3) gene disrupt its interaction with the COP9 signalosome, leading to WNK4 accumulation and potential kidney injury, but short-term experiments show no significant plasma electrolyte changes in DCT-specific knockout mice.
- Long-term DCT-specific deletion of CUL3 causes kidney injury and atrophy, indicating that CUL3's role in degrading WNK4 is crucial for preventing FHHt, highlighting how the
Structural bases for Na-Cl cotransporter inhibition by thiazide diuretic drugs and activation by kinases.
Nat Commun
August 2024
Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, USA.
Article Synopsis
- The Na-Cl cotransporter (NCC) is crucial for salt reabsorption in the kidneys, influencing electrolyte balance and blood pressure.
- Thiazide and thiazide-like diuretics, which inhibit NCC, have been key treatments for hypertension and edema since the 1950s.
- Research reveals that phosphorylation changes NCC's structure, creating an allosteric network that affects ion translocation, potentially explaining conditions like Familial Hyperkalemic Hypertension.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!