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Diuretics and calcium balance

Richard H Sterns, MD
Section Editor
Michael Emmett, MD
Deputy Editor
Albert Q Lam, MD


Most of the filtered calcium is reabsorbed throughout the nephron. This process involves two basic steps: (1) calcium is reabsorbed passively in the proximal tubule and loop of Henle down the favorable electrochemical gradients created by sodium and water reabsorption; and (2) calcium transport is actively regulated according to changes in calcium balance in the distal tubule and adjacent connecting segment (a small segment between the distal tubule and cortical collecting tubule) [1,2]. Parathyroid hormone (PTH) and calcitriol, the most active form of vitamin D, which may act in part by enhancing the activity of PTH, appear to stimulate this active process [1,3,4].

Calcium reabsorption and urinary calcium excretion can be affected by the administration of diuretics. Calcium excretion is increased by loop diuretics and diminished by thiazide-type diuretics and amiloride. How these effects occur is related to the mechanisms of sodium, chloride, and calcium transport in the different diuretic-sensitive segments. Ions cannot directly cross epithelial cell membranes. As a result, transcellular reabsorption of ions requires either the presence of transmembrane carriers or channels [5] or passage through the paracellular space between the tubular cells.


Filtered sodium chloride enters the cells in the thick ascending limb of the loop of Henle via Na-K-2Cl cotransporters in the luminal (or apical) membrane (figure 1) [5-7]. Although this process is electrically neutral, most of the reabsorbed potassium leaks back into the lumen to drive further sodium chloride transport [4]. This movement of cationic potassium into the lumen plus the movement of reabsorbed chloride (via a chloride channel) out of the cell into the peritubular capillary generates a net positive current from the capillary into the lumen. The ensuing lumen electropositivity creates an electrical gradient that promotes the passive reabsorption of cations (sodium and, to a lesser degree, calcium and magnesium) via the paracellular pathway between the cells [8].

Loop diuretics act by competing for the chloride site on the Na-K-2Cl cotransporter [5,6]. Inhibiting sodium chloride reabsorption also inhibits the backleak of potassium and the generation of the lumen-positive potential. As a result, calcium excretion rises, an effect that may be exploited in the treatment of hypercalcemia in selected patients. (See "Treatment of hypercalcemia", section on 'Saline hydration'.)

In neonates, the calciuresis induced by a loop diuretic may be deleterious since it can lead to the development of nephrocalcinosis. (See "Nephrocalcinosis in neonates", section on 'Pathogenesis'.)

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Literature review current through: Nov 2017. | This topic last updated: Sep 02, 2015.
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