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Renal ischemia-reperfusion injury impairs renal calcium, magnesium, and phosphate handling in mice

  • Manuel Meurer
  • Klaus HöcherlEmail author
Organ Physiology
  • 98 Downloads
Part of the following topical collections:
  1. Topical Collection: Organ Physiology

Abstract

Fibroblast growth factor 23 (FGF23) levels are elevated in patients with acute kidney injury (AKI). The consequences on renal Ca2+, Mg2+, and Pi regulatory mechanisms are unknown. We hypothesized that renal ischemia-reperfusion (I/R) injury alters the expression of important renal Ca2+, Mg2+, and Pi transport proteins. I/R injury was induced in male C57BL/6 mice by clamping both renal arteries for 27 min. Mice were investigated 18 h later. The mRNA and protein levels of renal Ca2+, Mg2+, and Pi transport proteins were measured by RT-qPCR and western blot analysis. I/R injury-induced hyperphosphatemia and hypermagnesemia were paralleled by a decrease in glomerular filtration rate and an increase in the fractional excretion of Ca2+, Mg2+, and Pi. I/R injury affected the fibroblast growth factor 23 (FGF23)-klotho-vitamin D axis by increasing plasma levels of FGF23 and downregulation of renal klotho expression. Plasma levels of PTH and 1,25-dihydroxyvitamin D3 were unchanged. Further, downregulation of key genes for paracellular reabsorption of Ca2+ and Mg2+ (claudin (Cldn)2, Cldn10b, Cldn16, Cldn19) and for active transcellular transport of Ca2+, Mg2+, and Pi (calbindin-D28K, Ncx1, Pmca4, Cnnm2, Trpm7, NaPi-2a, and NaPi-2c) was observed. However, renal expression of Trpv5 and Trpv6 was increased. In vitro studies support a direct effect of proinflammatory cytokines on the mRNA expression of Cldn16, Cldn19, and Trpv6. Our findings indicate that renal I/R injury increases FGF23 blood levels independent of PTH and 1,25-dihydroxyvitamin D3. This increase is associated with hypermagnesemia, hyperphosphatemia, and increased or decreased expression of specific renal Ca2+, Mg2+, and Pi transporters, respectively.

Keywords

Acute kidney injury Klotho FGF23 Inflammation Parathyroid hormone 

Notes

Acknowledgements

The technical assistance provided by Ramona Mogge and Andrea Agli is gratefully acknowledged.

Funding information

This study was supported by a grant from the Deutsche Forschungsgemeinschaft (DFG, SFB699/B5).

Compliance with ethical standards

All animal experiments were conducted according to the National Institutes of Health Guide for the Care and Use of Laboratory Animals and were approved by the local animal protection committee.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Institute of Experimental and Clinical Pharmacology and ToxicologyFriedrich-Alexander-Universität Erlangen-Nürnberg (FAU)ErlangenGermany

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