ArticleJournal of the American Society of Nephrology : JASN2016
Severe Salt-Losing Syndrome and Hyperkalemia Induced by Adult Nephron-Specific Knockout of the Epithelial Sodium Channel α-Subunit.
Article in Journal of the American Society of Nephrology : JASN, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 41 citations in OpenAlex.
- The kidney distal tubule potassium switch, modern diet and hypertension.Nature reviews. Nephrology · 2026Review
- Kidney-specific deletion of the BicC family RNA-binding protein 1 triggers an ADPKD-like cystogenic program.iScience · 2026Article
- Excess dietary sodium restores electrolyte and water homeostasis caused by loss of the endoplasmic reticulum molecular chaperone, GRP170, in the mouse nephron.American journal of physiology. Renal physiology · 2025Article
- Tmprss2 maintains epithelial barrier integrity and transepithelial sodium transport.Life science alliance · 2024Article
- Role of paraoxonase 3 in regulating ENaC-mediated NaThe Journal of physiology · 2024Article
- Excess dietary sodium partially restores salt and water homeostasis caused by loss of the endoplasmic reticulum molecular chaperone, GRP170, in the mouse nephron.bioRxiv : the preprint server for biology · 2024Article
- Mice lacking γENaC palmitoylation sites maintain benzamil-sensitive Na+ transport despite reduced channel activity.JCI insight · 2023Article
- Aldosterone: Renal Action and Physiological Effects.Comprehensive Physiology · 2023Article
- Mineralocorticoid Receptor Antagonists Cause Natriuresis in the Absence of Aldosterone.Hypertension (Dallas, Tex. : 1979) · 2022Article
- Kidney-Specific CAP1/Prss8-Deficient Mice Maintain ENaC-Mediated Sodium Balance through an Aldosterone Independent Pathway.International journal of molecular sciences · 2022Article
- The molecular chaperone GRP170 protects against ER stress and acute kidney injury in mice.JCI insight · 2022Article
- Selective Deletion of the Mechanistic Target of Rapamycin From the Renal Collecting Duct Principal Cell in Mice Down-Regulates the Epithelial Sodium Channel.Frontiers in physiology · 2021Article
- Interaction between Epithelial Sodium ChannelJournal of the American Society of Nephrology : JASN · 2020Article
- Physiological Processes Modulated by the Chloride-Sensitive WNK-SPAK/OSR1 Kinase Signaling Pathway and the Cation-Coupled Chloride Cotransporters.Frontiers in physiology · 2020Review
- The serine-threonine kinase PIM3 is an aldosterone-regulated protein in the distal nephron.Physiological reports · 2019Article
- Amiloride resolves resistant edema and hypertension in a patient with nephrotic syndrome; a case report.Physiological reports · 2018Article
- Intracellular Chloride and Scaffold Protein Mo25 Cooperatively Regulate Transepithelial Ion Transport through WNK Signaling in the Malpighian Tubule.Journal of the American Society of Nephrology : JASN · 2018Article
- RNA sequencing of kidney distal tubule cells reveals multiple mediators of chronic aldosterone action.Physiological genomics · 2018Article
- Plasma Potassium Determines NCC Abundance in Adult Kidney-SpecificJournal of the American Society of Nephrology : JASN · 2018Article
- Nephrotic Syndrome: Oedema Formation and Its Treatment With Diuretics.Frontiers in physiology · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Systemic pseudohypoaldosteronism type 1 (PHA-1) is a severe salt-losing syndrome caused by loss-of-function mutations of the amiloride-sensitive epithelial sodium channel (ENaC) and characterized by neonatal life-threatening hypovolemia and hyperkalemia. The very high plasma aldosterone levels detected under hypovolemic or hyperkalemic challenge can lead to increased or decreased sodium reabsorption, respectively, through the Na(+)/Cl(-) cotransporter (NCC). However, the role of ENaC deficiency remains incompletely defined, because constitutive inactivation of individual ENaC subunits is neonatally lethal in mice. We generated adult inducible nephron-specific αENaC-knockout mice (Scnn1a(Pax8/LC1)) that exhibit hyperkalemia and body weight loss when kept on a regular-salt diet, thus mimicking PHA-1. Compared with control mice fed a regular-salt diet, knockout mice fed a regular-salt diet exhibited downregulated expression and phosphorylation of NCC protein, despite high plasma aldosterone levels. In knockout mice fed a high-sodium and reduced-potassium diet (rescue diet), although plasma aldosterone levels remained significantly increased, NCC expression returned to control levels, and body weight, plasma and urinary electrolyte concentrations, and excretion normalized. Finally, shift to a regular diet after the rescue diet reinstated the symptoms of severe PHA-1 syndrome and significantly reduced NCC phosphorylation. In conclusion, lack of ENaC-mediated sodium transport along the nephron cannot be compensated for by other sodium channels and/or transporters, only by a high-sodium and reduced-potassium diet. We further conclude that hyperkalemia becomes the determining factor in regulating NCC activity, regardless of sodium loss, in the ENaC-mediated salt-losing PHA-1 phenotype.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.