Journal Article

Deletion of the Cl<sup>−</sup>/HCO<sub>3</sub><sup>−</sup> exchanger pendrin downregulates calcium-absorbing proteins in the kidney and causes calcium wasting

Sharon Barone, Hassane Amlal, Jie Xu and Manoocher Soleimani

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 27, issue 4, pages 1368-1379
Published in print April 2012 | ISSN: 0931-0509
Published online August 2011 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfr505
Deletion of the Cl−/HCO3− exchanger pendrin downregulates calcium-absorbing proteins in the kidney and causes calcium wasting

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Background.

The epithelial calcium channel (ECaC) (TRPV5) and the Cl/HCO3 exchanger pendrin (SLC26A4) are expressed on the apical membrane of tubular cells in the distal nephron and play essential roles in calcium re-absorption and bicarbonate secretion, respectively, in the kidney.

Methods.

A combination of functional and molecular biology techniques were employed to examine the role of pendrin deletion in calcium excretion.

Results.

Here, we demonstrate that deletion of pendrin causes acidic urine [urine pH 4.9 in knockout (KO) versus 5.9 in wild-type (WT) mice, P < 0.03)] and downregulates the calcium-absorbing molecules ECaC and Na/Ca exchanger in the kidney, as shown by northern hybridization, immunoblot analysis and/or immunofluorescent labeling. These changes were associated with a ∼100% increase in 24-h urine calcium excretion in pendrin null mice. Subjecting the pendrin WT and KO mice to oral bicarbonate loading for 12 days increased the urine pH to ∼8 in both genotypes, normalized the expression of ECaC and Na/Ca exchanger and reduced the urine calcium excretion in pendrin-null mice to levels comparable to WT mice.

Conclusions.

We suggest that pendrin dysfunction should be suspected and investigated in humans with an otherwise unexplained acidic urine and hypercalciuria.

Keywords: acid-base transporters; acidic urine; calcium excretion; distal nephron; urine alkalinization

Journal Article.  6071 words.  Illustrated.

Subjects: Nephrology

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