ArticleThe Journal of clinical investigation2017
Phenotypic and pharmacogenetic evaluation of patients with thiazide-induced hyponatremia.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.
- The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019).Hypertension research : official journal of the Japanese Society of Hypertension · 2019Guideline
- Effects of Hydrochlorothiazide and Metformin on Aquaresis and Nephroprotection by a Vasopressin V2 Receptor Antagonist in ADPKD: A Randomized Crossover Trial.Clinical journal of the American Society of Nephrology : CJASN · 2022Trial
- A Randomized Trial of Distal Diuretics versus Dietary Sodium Restriction for Hypertension in Chronic Kidney Disease.Journal of the American Society of Nephrology : JASN · 2020Trial
- SGLT2 inhibitors in autosomal dominant polycystic kidney disease: rationale, evidence gaps, and ongoing clinical trials.International urology and nephrology · 2026Review
- Hyponatraemia in Neck of Femur Fracture: A Narrative Review of Epidemiology, Pathophysiology, and Outcomes.Geriatrics (Basel, Switzerland) · 2026Review
- Hyponatraemia in ageing.Nature reviews. Endocrinology · 2025Review
- Genome-Wide Association Study of Plasma Sodium Concentrations with and without Exposure to Thiazide Diuretics.Journal of the American Society of Nephrology : JASN · 2025Article
- Thiazide-Associated Hyponatremia: A Retrospective Cohort Study Comparing Hydrochlorothiazide Versus Indapamide Versus Chlorthalidone.Journal of clinical hypertension (Greenwich, Conn.) · 2025Article
- The biology of water homeostasis.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Review
- Organic anion transporting polypeptides: Pharmacology, toxicology, structure, and transport mechanisms.Pharmacological reviews · 2025Review
- Evaluation of hyponatremia among older adults exposed to selective serotonin reuptake inhibitors and thiazide diuretics.Pharmacotherapy · 2025Article
- Pathophysiology, symptoms, outcomes, and evaluation of hyponatremia: comprehension and best clinical practice.Clinical and experimental nephrology · 2025Review
- Cosmic kidney disease: a spaceflight-induced tubulopathy.Clinical kidney journal · 2024Article
- Expression levels and stoichiometry of Hnf1β, Emx2, Pax8 and Hnf4 influence direct reprogramming of induced renal tubular epithelial cells.Cell regeneration (London, England) · 2024Article
- The Effect of Thiazide Diuretics on Urinary Prostaglandin E2 Excretion and Serum Sodium in the General Population.The Journal of clinical endocrinology and metabolism · 2024Article
- Cosmic kidney disease: an integrated pan-omic, physiological and morphological study into spaceflight-induced renal dysfunction.Nature communications · 2024Article
- Euvolemic hypotonic hyponatremia in SIAD and thiazide-treated patients: similarities and differences.Journal of nephrology · 2024Article
- Urinary Prostaglandin E2 Excretion and the Risk of Cardiovascular and Kidney Disease.Journal of the American Heart Association · 2024Article
- Label-free detection of prostaglandin transporter (SLCO2A1) function and inhibition: insights by wound healing and TRACT assays.Frontiers in pharmacology · 2024Article
- Syndrome of Inappropriate Antidiuresis: From Pathophysiology to Management.Endocrine reviews · 2023Review
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Authors and funding
19 authors at 7 institutions in 3 countries.
Funding
Abstract
Thiazide diuretics are among the most widely used treatments for hypertension, but thiazide-induced hyponatremia (TIH), a clinically significant adverse effect, is poorly understood. Here, we have studied the phenotypic and genetic characteristics of patients hospitalized with TIH. In a cohort of 109 TIH patients, those with severe TIH displayed an extended phenotype of intravascular volume expansion, increased free water reabsorption, urinary prostaglandin E2 excretion, and reduced excretion of serum chloride, magnesium, zinc, and antidiuretic hormone. GWAS in a separate cohort of 48 TIH patients and 2,922 controls from the 1958 British birth cohort identified an additional 14 regions associated with TIH. We identified a suggestive association with a variant in SLCO2A1, which encodes a prostaglandin transporter in the distal nephron. Resequencing of SLCO2A1 revealed a nonsynonymous variant, rs34550074 (p.A396T), and association with this SNP was replicated in a second cohort of TIH cases. TIH patients with the p.A396T variant demonstrated increased urinary excretion of prostaglandin E2 and metabolites. Moreover, the SLCO2A1 phospho-mimic p.A396E showed loss of transporter function in vitro. These findings indicate that the phenotype of TIH involves a more extensive metabolic derangement than previously recognized. We propose one mechanism underlying TIH development in a subgroup of patients in which SLCO2A1 regulation is altered.
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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.