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Thiazide Therapy in Chronic Kidney Disease: Renal and Extra Renal Targets

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Background: Thiazides are the most commonly used medications for the treatment of mild and moderate hypertension. Despite their recognized effect, the mechanism by which thiazides reduce systemic blood pressure remains uncertain. The prevailing belief is that thiazides reduce blood pressure primarily via enhancement of salt excretion consequent to the inhibition of the Na-Cl Cotransporter (NCC) in the Distal Convoluted Tubules (DCT). However, recent reports point to a reduction in peripheral vascular resistance as a major mechanism of antihypertensive effect of thiazides. It is plausible that both mechanisms, renal and extra-renal, may be operating simultaneously. Recent studies point to compensatory mechanisms in the kidney distal nephron that may play a role in blunting the diuretic effect of thiazides. Not much information is available about the efficacy of thiazides in controlling blood pressure in individuals with Chronic Kidney Disease (CKD).

Objective: This review will discuss the latest updates on the use and efficacy of thiazides derivatives as diuretics and antihypertensive medications in CKD patients.

Conclusion: Thiazides remain effective as diuretics and antihypertensive agents in individuals with low GFR.
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Keywords: Diuretics; Na-Cl cotransport (SLC12A3); Pendrin (SLC26A4); hypertension; kidney disease; kidney tubules; thiazides

Document Type: Review Article

Publication date: October 1, 2018

This article was made available online on July 19, 2018 as a Fast Track article with title: "Thiazide Therapy in Chronic Kidney Disease: Renal and Extra Renal Targets".

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  • Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism and disposition. The journal serves as an international forum for the publication of timely reviews in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments. The journal covers the following areas:

    In vitro systems including CYP-450; enzyme induction and inhibition; drug-drug interactions and enzyme kinetics; pharmacokinetics, toxicokinetics, species scaling and extrapolations; P-glycoprotein and transport carriers; target organ toxicity and interindividual variability; drug metabolism and disposition studies; extrahepatic metabolism; phase I and phase II metabolism; recent developments for the identification of drug metabolites and adducts.
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