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Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Pflugers+Arch 2019 ; 471 (6): 901-914 Nephropedia Template TP
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Renal ischemia-reperfusion injury impairs renal calcium, magnesium, and phosphate handling in mice #MMPMID30685787
Meurer M; Hocherl K
Pflugers Arch 2019[Jun]; 471 (6): 901-914 PMID30685787show ga
Fibroblast growth factor 23 (FGF23) levels are elevated in patients with acute kidney injury (AKI). The consequences on renal Ca(2+), Mg(2+), and P(i) regulatory mechanisms are unknown. We hypothesized that renal ischemia-reperfusion (I/R) injury alters the expression of important renal Ca(2+), Mg(2+), and P(i) 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 Ca(2+), Mg(2+), and P(i) 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 Ca(2+), Mg(2+), and P(i). 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 D(3) were unchanged. Further, downregulation of key genes for paracellular reabsorption of Ca(2+) and Mg(2+) (claudin (Cldn)2, Cldn10b, Cldn16, Cldn19) and for active transcellular transport of Ca(2+), Mg(2+), and P(i) (calbindin-D(28K), Ncx1, Pmca4, Cnnm2, Trpm7, NaP(i)-2a, and NaP(i)-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 D(3). This increase is associated with hypermagnesemia, hyperphosphatemia, and increased or decreased expression of specific renal Ca(2+), Mg(2+), and P(i) transporters, respectively.