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The mechanism of hypocalciuria with NaCl cotransporter inhibition

Nature Reviews Nephrology volume 7, pages 669–674 (2011)Cite this article

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Abstract

Thiazide diuretics are used to prevent the recurrence of calcium-containing kidney stones. The ability of these drugs to reduce urinary calcium excretion has a key role in this process. Although studies have shown a reduction in the recurrence rate of calcium-containing stones in patients treated with thiazides, whether hypocalciuria results from increased calcium reabsorption in the proximal or distal nephron is still unclear. When extracellular fluid volume is considerably reduced, the proximal tubule is likely to have a major role in thiazide-induced hypocalciuria. This process frequently occurs when high doses of thiazides and sodium restriction are prescribed for the treatment of kidney stone disease. The distal tubule is predominantly involved in NaCl cotransporter inhibition-induced hypocalciuria when the extracellular fluid volume is not reduced, a clinical scenario observed in patients with Gitelman syndrome. In this Perspectives article, we discuss the evidence supporting the hypocalciuric effects of NaCl cotransporter inhibition in the proximal and distal nephron.

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Figure 1: An overview of calcium reabsorption in the nephron.
Figure 2: Potential mechanisms for thiazide diuretics to decrease reabsorption of calcium in the distal tubule.

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Authors and Affiliations

  1. Department of Medicine, VA North Texas Health Care System, The University of Texas Southwestern Medical Center at Dallas, 4500 South Lancaster Road, Dallas, 75390-8856, TX, USA

    Robert F. Reilly

  2. Nephrology Division, The University of Texas Southwestern Medical Center at Dallas, 4500 South Lancaster Road, Dallas, 75390-8856, TX, USA

    Chou-Long Huang

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R. F. Reilly and C.-L. Huang contributed equally to discussion of content for the article, researching data to include in the manuscript and reviewing and editing of the manuscript before submission.

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Correspondence to Robert F. Reilly.

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Reilly, R., Huang, CL. The mechanism of hypocalciuria with NaCl cotransporter inhibition. Nat Rev Nephrol 7, 669–674 (2011). https://doi.org/10.1038/nrneph.2011.138

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