title: Effect of diuretics on renal tubular transport of calcium and magnesium.
abstract: Calcium (Ca2+) and Magnesium (Mg2+) reabsorption along the renal tubule is dependent on distinct trans- and paracellular pathways. Our understanding of the molecular machinery involved is increasing. Ca2+and Mg2+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 Ca2+and Mg2+transport. Alterations in these molecular constituents can have profound effects on tubular Ca2+and Mg2+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+) transport, but also indirectly affect renal Ca2+and Mg2+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 Ca2+and Mg2+handling are reviewed in the context of the present understanding of basal molecular mechanisms of Ca2+and Mg2+transport. Acetazolamide, osmotic diuretics, Na+/H+exchanger (NHE3) inhibitors, and antidiabetic Na+/glucose cotransporter type 2 (SGLT) blocking compounds, target the proximal tubule, where paracellular Ca2+transport predominates. Loop diuretics and renal outer medullary K+(ROMK) inhibitors block thick ascending limb transport, a segment with significant paracellular Ca2+and Mg2+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+transport at distal sites, can also affect divalent cation transport.
authors.affiliation: Membrane Protein Disease Research Group, Department of Physiology, University of Alberta, Edmonton, Canada.|Department of Pediatrics, University of Alberta, Edmonton, Canada; and.
authors.forename: R Todd
authors.initials: RT
authors.lastname: Alexander
authors.affiliation: Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark hdimke@health.sdu.dk.
authors.forename: Henrik
authors.identifier: 0000-0002-9170-2168
authors.initials: H
authors.lastname: Dimke
mesh_terms: D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D004232:Diuretics / Q000627:therapeutic use*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism*; D065608:Renal Reabsorption / Q000187:drug effects*
chemical_list: D004232:Diuretics; D008274:Magnesium; D002118:Calcium
keywords: TRPM6 and TRPV5 channels; amiloride; calciuria; claudins; furosemide