Clinical and Genetic Factors Associated With Thiazide-Induced Hyponatremia

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Thiazide diuretics are associated with an increased risk of hyponatremia. The aim of this study was to investigate possible predictors of thiazide-induced hyponatremia.

A total of 48 patients admitted to the ward or to the emergency department due to severe thiazide-induced hyponatremia (Na < 125 mmol/L) were enrolled in our study as the case group. Another 211 hypertensive patients with normal sodium levels after treatment with thiazide diuretics were selected as the control group. Twelve tag single nucleotide polymorphism markers were selected from the Potassium Channel, Inwardly Rectifying Subfamily J, Member 1 ( KCNJ1) gene: rs1231254, rs2238009, rs1148058, rs675482, rs673614, rs12795437, rs2855800, rs2509585, rs3016774, rs881333, rs4529890, and rs7116606. Clinical and genetic parameters between patients with thiazide-induced hyponatremia and the control group were compared. Logistic regression was used to analyze data.

The patients with thiazide-induced hyponatremia were older ( P < 0.001), predominantly female ( P = 0.008), had a lower mean body mass index (BMI) ( P < 0.001), and more commonly used angiotensin II receptor antagonist ( P < 0.001) and spironolactone ( P = 0.007) compared with the control groups. Analysis with multivariate logistic regression revealed that age (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.08–1.19, P < 0.001), female gender (OR, 4.49; 95% CI, 1.54–13.11, P = 0.006), BMI (OR, 0.80; 95% CI, 0.69–0.93, P = 0.003), and KCNJ1 rs2509585 C/T or T/T polymorphisms (OR, 5.75; 95% CI, 1.25–26.45, P = 0.03) were independent predictors for thiazide-induced hyponatremia.

Older female patients with lower BMIs and KCNJ1 rs2509585 C/T or T/T polymorphisms were more likely to develop thiazide-induced hyponatremia.

Related collections

Most cited references 26

Record: found
Abstract: found
Article: not found

Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

(2002)

Antihypertensive therapy is well established to reduce hypertension-related morbidity and mortality, but the optimal first-step therapy is unknown. To determine whether treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor lowers the incidence of coronary heart disease (CHD) or other cardiovascular disease (CVD) events vs treatment with a diuretic. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind, active-controlled clinical trial conducted from February 1994 through March 2002. A total of 33 357 participants aged 55 years or older with hypertension and at least 1 other CHD risk factor from 623 North American centers. Participants were randomly assigned to receive chlorthalidone, 12.5 to 25 mg/d (n = 15 255); amlodipine, 2.5 to 10 mg/d (n = 9048); or lisinopril, 10 to 40 mg/d (n = 9054) for planned follow-up of approximately 4 to 8 years. The primary outcome was combined fatal CHD or nonfatal myocardial infarction, analyzed by intent-to-treat. Secondary outcomes were all-cause mortality, stroke, combined CHD (primary outcome, coronary revascularization, or angina with hospitalization), and combined CVD (combined CHD, stroke, treated angina without hospitalization, heart failure [HF], and peripheral arterial disease). Mean follow-up was 4.9 years. The primary outcome occurred in 2956 participants, with no difference between treatments. Compared with chlorthalidone (6-year rate, 11.5%), the relative risks (RRs) were 0.98 (95% CI, 0.90-1.07) for amlodipine (6-year rate, 11.3%) and 0.99 (95% CI, 0.91-1.08) for lisinopril (6-year rate, 11.4%). Likewise, all-cause mortality did not differ between groups. Five-year systolic blood pressures were significantly higher in the amlodipine (0.8 mm Hg, P =.03) and lisinopril (2 mm Hg, P<.001) groups compared with chlorthalidone, and 5-year diastolic blood pressure was significantly lower with amlodipine (0.8 mm Hg, P<.001). For amlodipine vs chlorthalidone, secondary outcomes were similar except for a higher 6-year rate of HF with amlodipine (10.2% vs 7.7%; RR, 1.38; 95% CI, 1.25-1.52). For lisinopril vs chlorthalidone, lisinopril had higher 6-year rates of combined CVD (33.3% vs 30.9%; RR, 1.10; 95% CI, 1.05-1.16); stroke (6.3% vs 5.6%; RR, 1.15; 95% CI, 1.02-1.30); and HF (8.7% vs 7.7%; RR, 1.19; 95% CI, 1.07-1.31). Thiazide-type diuretics are superior in preventing 1 or more major forms of CVD and are less expensive. They should be preferred for first-step antihypertensive therapy.

0 comments Cited 255 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group.

JL Probstfield (1991)

To assess the ability of antihypertensive drug treatment to reduce the risk of nonfatal and fatal (total) stroke in isolated systolic hypertension. Multicenter, randomized, double-blind, placebo-controlled. Community-based ambulatory population in tertiary care centers. 4736 persons (1.06%) from 447,921 screenees aged 60 years and above were randomized (2365 to active treatment, 2371 to placebo). Systolic blood pressure ranged from 160 to 219 mm Hg and diastolic blood pressure was less than 90 mm Hg. Of the participants, 3161 were not receiving antihypertensive medication at initial contact, and 1575 were. The average systolic blood pressure was 170 mm Hg; average diastolic blood pressure, 77 mm Hg. The mean age was 72 years, 57% were women, and 14% were black. --Participants were stratified by clinical center and by antihypertensive medication status at initial contact. For step 1 of the trial, dose 1 was chlorthalidone, 12.5 mg/d, or matching placebo; dose 2 was 25 mg/d. For step 2, dose 1 was atenolol, 25 mg/d, or matching placebo; dose 2 was 50 mg/d. Primary. Nonfatal and fatal (total) stroke. Secondary. Cardiovascular and coronary morbidity and mortality, all-cause mortality, and quality of life measures. Average follow-up was 4.5 years. The 5-year average systolic blood pressure was 155 mm Hg for the placebo group and 143 mm Hg for the active treatment group, and the 5-year average diastolic blood pressure was 72 and 68 mm Hg, respectively. The 5-year incidence of total stroke was 5.2 per 100 participants for active treatment and 8.2 per 100 for placebo. The relative risk by proportional hazards regression analysis was 0.64 (P = .0003). For the secondary end point of clinical nonfatal myocardial infarction plus coronary death, the relative risk was 0.73. Major cardiovascular events were reduced (relative risk, 0.68). For deaths from all causes, the relative risk was 0.87. In persons aged 60 years and over with isolated systolic hypertension, antihypertensive stepped-care drug treatment with low-dose chlorthalidone as step 1 medication reduced the incidence of total stroke by 36%, with 5-year absolute benefit of 30 events per 1000 participants. Major cardiovascular events were reduced, with 5-year absolute benefit of 55 events per 1000.

0 comments Cited 182 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Genetic heterogeneity of Bartter's syndrome revealed by mutations in the K+ channel, ROMK.

Fiona Karet Frankl, Ron Simon, J Soriano … (1996)

Mutations in the Na-K-2Cl cotransporter (NKCC2), a mediator of renal salt reabsorption, cause Bartter's syndrome, featuring salt wasting, hypokalaemic alkalosis, hypercalciuria and low blood pressure. NKCC2 mutations can be excluded in some Bartter's kindreds, prompting examination of regulators of cotransporter activity. One regulator is believed to be ROMK, an ATP-sensitive K+ channel that 'recycles' reabsorbed K+ back to the tubule lumen. Examination of the ROMK gene reveals mutations that co-segregate with the disease and disrupt ROMK function in four Bartter's kindreds. Our findings establish the genetic heterogeneity of Bartter's syndrome, and demonstrate the physiologic role of ROMK in vivo.

0 comments Cited 111 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Medicine (Baltimore)

Journal ID (iso-abbrev): Medicine (Baltimore)

Journal ID (publisher-id): MEDI

Title: Medicine

Publisher: Wolters Kluwer Health

ISSN (Print): 0025-7974

ISSN (Electronic): 1536-5964

Publication date Collection: August 2015

Publication date (Electronic): 28 August 2015

Volume: 94

Issue: 34

Electronic Location Identifier: e1422

Affiliations

From the Department of Medical Education (C-CH); Department of Medical Research (S-JL, J-WC); Division of Cardiology, Department of Medicine (C-CH, H-BL, P-HH, C-CC, T-CW, S-JL, J-WC); Healthcare and Management Center (H-BL); Division of Endocrinology and Metabolism, Department of Medicine (L-YL); Division of Nephrology, Department of Medicine (C-CL, C-YY, S-yL); Department of Emergency Medicine, Taipei Veterans General Hospital (Y-CC); Cardiovascular Research Center (C-CH, H-BL, P-HH, C-CC, T-CW, S-JL, J-WC); Institute of Pharmacology (C-CH, S-IH, L-YL, J-WC); Institute of Clinical Medicine, National Yang-Ming University (H-BL, P-HH, T-CW, S-JL); Institute of Biomedical Sciences, Academia Sinica (W-HP); Institute of Epidemiology, School of Public Health, National Taiwan University, Taipei (W-HP); Environment-Omics-Disease Research Centre, China Medical University Hospital (C-MC); Graduate Institute of Clinical Medical Science, China Medical University, Taichung (C-MC); and Institute of Population Health Science, National Health Research Institutes, Miaoli, Taiwan, R.O.C. (W-HP).

Author notes

Correspondence: Jaw-Wen Chen, Department of Medical Research, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Taipei, Taiwan, R.O.C. (e-mail: jwchen@ 123456vghtpe.gov.tw ).

Article

Accession ID: 01422

DOI: 10.1097/MD.0000000000001422

PMC ID: 4602917

PubMed ID: 26313793

SO-VID: cfdc1778-db22-45ae-baab-9dc92c1c466e

License:

This is an open access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0, where it is permissible to download, share and reproduce the work in any medium, provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/4.0

History

Date received : 17 May 2015

Date revision received : 8 July 2015

Date accepted : 27 July 2015

Custom metadata

OPEN-ACCESS TRUE

Data availability:

Comments

Comment on this article

scite_

Cited by 6

See all cited by

Most referenced authors 500

See all reference authors

Clinical and Genetic Factors Associated With Thiazide-Induced Hyponatremia

Read this article at

Abstract

Related collections

Wits Journal of Clinical Medicine

Most cited references 26

Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group.

Genetic heterogeneity of Bartter's syndrome revealed by mutations in the K+ channel, ROMK.

Author and article information

Journal

Affiliations

Author notes

Article

History

Categories

Custom metadata

Comments

Comment on this article

Similar content 326

Cited by 6

Most referenced authors 500