Renal ischemia-reperfusion injury impairs renal calcium, magnesium, and phosphate handling in mice
Meurer M, Höcherl K (2019)
Publication Type: Journal article
Publication year: 2019
Journal
Book Volume: 471
Pages Range: 901-914
Journal Issue: 6
DOI: 10.1007/s00424-019-02255-6
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.
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How to cite
APA:
Meurer, M., & Höcherl, K. (2019). Renal ischemia-reperfusion injury impairs renal calcium, magnesium, and phosphate handling in mice. Pflügers Archiv: European Journal of Physiology, 471(6), 901-914. https://doi.org/10.1007/s00424-019-02255-6
MLA:
Meurer, Manuel, and Klaus Höcherl. "Renal ischemia-reperfusion injury impairs renal calcium, magnesium, and phosphate handling in mice." Pflügers Archiv: European Journal of Physiology 471.6 (2019): 901-914.
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