ArticleProceedings of the National Academy of Sciences of the United States of America2012
Double knockout of pendrin and Na-Cl cotransporter (NCC) causes severe salt wasting, volume depletion, and renal failure.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 117 citations in OpenAlex.
- Pendrin inhibitor PDSinh-C01 reverses salt-sensitive hypertension and metabolic acidosis in the 5/6 nephrectomy rat model.Pflugers Archiv : European journal of physiology · 2026Article
- Loop Diuretic Dose Intensification versus Adjuvant Thiazide for Diuretic Resistance in Acute Heart Failure: Mechanistic Randomized Controlled Trial.Journal of the American Society of Nephrology : JASN · 2026Article
- Diuretics in patients with chronic kidney disease.Nature reviews. Nephrology · 2025Review
- Deciphering the function of the fifth class of Gα proteins: regulation of ionic homeostasis as unifying hypothesis.Cellular and molecular life sciences : CMLS · 2024Article
- Pendrin: linking acid base to blood pressure.Pflugers Archiv : European journal of physiology · 2024Review
- The Changing Role of Loop Diuretics in Heart Failure Management across the Last Century.Journal of clinical medicine · 2024Review
- SLC26 Anion Transporters.Handbook of experimental pharmacology · 2024Review
- Metabolic alkalosis in cystic fibrosis: from vascular volume depletion to impaired bicarbonate excretion.Frontiers in endocrinology · 2024Review
- Kidney and blood pressure regulation-latest evidence for molecular mechanisms.Clinical kidney journal · 2023Review
- Control of sodium and potassium homeostasis by renal distal convoluted tubules.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2023Article
- Kidney ion handling genes and their interaction in blood pressure control.Bioscience reports · 2022Review
- Metabolic Alkalosis Pathogenesis, Diagnosis, and Treatment: Core Curriculum 2022.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2022Review
- Regulation of distal tubule sodium transport: mechanisms and roles in homeostasis and pathophysiology.Pflugers Archiv : European journal of physiology · 2022Review
- Activation of 2-oxoglutarate receptor 1 (OXGR1) by α-ketoglutarate (αKG) does not detectably stimulate Pendrin-mediated anion exchange in Xenopus oocytes.Physiological reports · 2022Article
- Pendrin-null mice develop severe hypokalemia following dietary NaAmerican journal of physiology. Renal physiology · 2022Article
- Regulation of Blood Pressure and Salt Balance By Pendrin-Positive Intercalated Cells: Donald Seldin Lecture 2020.Hypertension (Dallas, Tex. : 1979) · 2022Review
- Characterization of pendrin in urinary extracellular vesicles in a rat model of aldosterone excess and in human primary aldosteronism.Hypertension research : official journal of the Japanese Society of Hypertension · 2021Article
- Renal tubular transport protein regulation in primary aldosteronism: can large-scale proteomic analysis offer a new insight?Journal of human hypertension · 2021Article
- The ClJournal of human hypertension · 2021Article
- Urinary Extracellular Vesicles for Renal Tubular Transporters Expression in Patients With Gitelman Syndrome.Frontiers in medicine · 2021Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The Na-Cl cotransporter (NCC), which is the target of inhibition by thiazides, is located in close proximity to the chloride-absorbing transporter pendrin in the kidney distal nephron. Single deletion of pendrin or NCC does not cause salt wasting or excessive diuresis under basal conditions, raising the possibility that these transporters are predominantly active during salt depletion or in response to excess aldosterone. We hypothesized that pendrin and NCC compensate for loss of function of the other under basal conditions, thereby masking the role that each plays in salt absorption. To test our hypothesis, we generated pendrin/NCC double knockout (KO) mice by crossing pendrin KO mice with NCC KO mice. Pendrin/NCC double KO mice displayed severe salt wasting and sharp increase in urine output under basal conditions. As a result, animals developed profound volume depletion, renal failure, and metabolic alkalosis without hypokalemia, which were all corrected with salt replacement. We propose that the combined inhibition of pendrin and NCC can provide a strong diuretic regimen without causing hypokalemia for patients with fluid overload, including patients with congestive heart failure, nephrotic syndrome, diuretic resistance, or generalized edema.
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