Mechanism of Urinary Calcium Regulation by Urinary Magnesium and pH

Olivier Bonny; Adam Rubin; Chou-Long Huang; William H. Frawley; Charles Y.C. Pak; Orson W. Moe

doi:10.1681/ASN.2007091038

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Mechanism of Urinary Calcium Regulation by Urinary Magnesium and pH

Journal article

Open access

Peer reviewed

Mechanism of Urinary Calcium Regulation by Urinary Magnesium and pH

Olivier Bonny, Adam Rubin, Chou-Long Huang, William H. Frawley, Charles Y.C. Pak and Orson W. Moe

Journal of the American Society of Nephrology, Vol.19(8), pp.1530-1537

08/01/2008

DOI: 10.1681/ASN.2007091038

PMCID: PMC2488265

PMID: 18448585

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Abstract

Urinary magnesium and pH are known to modulate urinary calcium excretion, but the mechanisms underlying these relationships are unknown. In this study, the data from 17 clinical trials in which urinary magnesium and pH were pharmacologically manipulated were analyzed, and it was found that the change in urinary calcium excretion is directly proportional to the change in magnesium excretion and inversely proportional to the change in urine pH; a regression equation was generated to relate these variables ( R 2 = 0.58). For further exploration of these relationships, intravenous calcium chloride, magnesium chloride, or vehicle was administered to rats. Magnesium infusion significantly increased urinary calcium excretion (normalized to urinary creatinine), but calcium infusion did not affect magnesium excretion. Parathyroidectomy did not prevent this magnesium-induced hypercalciuria. The effect of magnesium loading on calciuria was still observed after treatment with furosemide, which disrupts calcium and magnesium absorption in the thick ascending limb, suggesting that the effect may be mediated by the distal nephron. The calcium channel TRPV5, normally present in the distal tubule, was expressed in Xenopus oocytes. Calcium uptake by TRPV5 was directly inhibited by magnesium and low pH. In summary, these data are compatible with the hypothesis that urinary magnesium directly inhibits renal calcium absorption, which can be negated by high luminal pH, and that this regulation likely takes place in the distal tubule.

Basic Research

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Title: Subtitle: Mechanism of Urinary Calcium Regulation by Urinary Magnesium and pH
Creators: Olivier Bonny - The University of Texas Southwestern Medical Center
Adam Rubin - The University of Texas Southwestern Medical Center
Chou-Long Huang - The University of Texas Southwestern Medical Center
William H. Frawley - The University of Texas Southwestern Medical Center
Charles Y.C. Pak - The University of Texas Southwestern Medical Center
Orson W. Moe - The University of Texas Southwestern Medical Center
Resource Type: Journal article
Publication Details: Journal of the American Society of Nephrology, Vol.19(8), pp.1530-1537
DOI: 10.1681/ASN.2007091038
PMID: 18448585
PMCID: PMC2488265
NLM abbreviation: J Am Soc Nephrol
ISSN: 1046-6673
eISSN: 1533-3450
Publisher: American Society of Nephrology
Language: English
Date published: 08/01/2008
Academic Unit: Nephrology; Internal Medicine
Record Identifier: 9984359696902771

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