Effect of diuretics on renal tubular transport of calcium and magnesium

<jats:p>Calcium (Ca<jats:sup>2+</jats:sup>) and Magnesium (Mg<jats:sup>2+</jats:sup>) reabsorption along the renal tubule is dependent on distinct trans- and paracellular pathways. Our understanding of the molecular machinery involved is increasing. Ca<jats:sup>2+</jats:sup>and Mg<jats:sup>2+</jats:sup>reclamation in kidney is dependent on a diverse array of proteins, which are important for both forming divalent cation-permeable pores and channels, but also for generating the necessary driving forces for Ca<jats:sup>2+</jats:sup>and Mg<jats:sup>2+</jats:sup>transport. Alterations in these molecular constituents can have profound effects on tubular Ca<jats:sup>2+</jats:sup>and Mg<jats:sup>2+</jats:sup>handling. Diuretics are used to treat a large range of clinical conditions, but most commonly for the management of blood pressure and fluid balance. The pharmacological targets of diuretics generally directly facilitate sodium (Na<jats:sup>+</jats:sup>) transport, but also indirectly affect renal Ca<jats:sup>2+</jats:sup>and Mg<jats:sup>2+</jats:sup>handling, i.e., by establishing a prerequisite electrochemical gradient. It is therefore not surprising that substantial alterations in divalent cation handling can be observed following diuretic treatment. The effects of diuretics on renal Ca<jats:sup>2+</jats:sup>and Mg<jats:sup>2+</jats:sup>handling are reviewed in the context of the present understanding of basal molecular mechanisms of Ca<jats:sup>2+</jats:sup>and Mg<jats:sup>2+</jats:sup>transport. Acetazolamide, osmotic diuretics, Na<jats:sup>+</jats:sup>/H<jats:sup>+</jats:sup>exchanger (NHE3) inhibitors, and antidiabetic Na<jats:sup>+</jats:sup>/glucose cotransporter type 2 (SGLT) blocking compounds, target the proximal tubule, where paracellular Ca<jats:sup>2+</jats:sup>transport predominates. Loop diuretics and renal outer medullary K<jats:sup>+</jats:sup>(ROMK) inhibitors block thick ascending limb transport, a segment with significant paracellular Ca<jats:sup>2+</jats:sup>and Mg<jats:sup>2+</jats:sup>transport. Thiazides target the distal convoluted tubule; however, their effect on divalent cation transport is not limited to that segment. Finally, potassium-sparing diuretics, which inhibit electrogenic Na<jats:sup>+</jats:sup>transport at distal sites, can also affect divalent cation transport.</jats:p>