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Nephrol Dial Transplant. 2018 Dec 7. doi: 10.1093/ndt/gfy358. [Epub ahead of print]

Low magnesium diet aggravates phosphate-induced kidney injury.

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Department of Inter-Organ Communication Research in Kidney Disease, Osaka University Graduate School of Medicine, Osaka, Japan.
Department of Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan.



Magnesium is known to protect against phosphate-induced tubular cell injuries in vitro. We investigated in vivo effects of magnesium on kidney injuries and phosphate metabolism in mice exposed to a high phosphate diet.


Heminephrectomized mice were maintained on a high phosphate/normal magnesium diet or a high phosphate/low magnesium diet for 6 weeks. We compared renal histology, phosphaturic hormones and renal α-Klotho expression between the two diet groups.


High phosphate diet-induced tubular injuries and interstitial fibrosis were remarkably aggravated by the low-magnesium diet. At 1 week after high phosphate feeding when serum creatinine levels were similar between the two groups, the low magnesium diet suppressed not only fecal phosphate excretion but also urinary phosphate excretion, resulting in increased serum phosphate levels. Parathyroid hormone (PTH) levels were not appropriately elevated in the low magnesium diet group despite lower 1,25-dihydroxyvitamin D and serum calcium levels compared with the normal magnesium diet group. Although fibroblast growth factor 23 (FGF23) levels were lower in the low magnesium diet group, calcitriol-induced upregulation of FGF23 could not restore the impaired urinary phosphate excretion. The low magnesium diet markedly downregulated α-Klotho expression in the kidney. This downregulation of α-Klotho occurred even when mice were fed the low phosphate diet.


A low magnesium diet aggravated high phosphate diet-induced kidney injuries. Impaired PTH secretion and downregulation of renal α-Klotho were likely to be involved in the blunted urinary phosphate excretion by the low magnesium diet. Increasing dietary magnesium may be useful to attenuate phosphate-induced kidney injury.


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