Phosphate binding by sucroferric oxyhydroxide ameliorates renal injury in the remnant kidney model

Yoshikazu Nemoto, Takanori Kumagai, Kenichi Ishizawa, Yutaka Miura, Takeshi Shiraishi, Chikayuki Morimoto, Kazuhiro Sakai, Hiroki Omizo, Osamu Yamazaki, Yoshifuru Tamura, Yoshihide Fujigaki, Hiroshi Kawachi, Makoto Kuro-o, Shunya Uchida, Shigeru Shibata

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Abstract

Recent clinical studies indicate that the disturbed phosphate metabolism in chronic kidney disease (CKD) may facilitate kidney injury; nonetheless, the causal role of phosphate in CKD progression remains to be elucidated. Here, we show that intestinal phosphate binding by sucroferric oxyhydroxide (SF) ameliorates renal injury in the rat remnant kidney model. Sprague-Dawley rats received 5/6 nephrectomy (RK) and had a normal chow or the same diet containing SF (RK + SF). RK rats showed increased plasma FGF23 and phosphate levels, which were suppressed by SF administration. Of note, albuminuria in RK rats was significantly ameliorated by SF at both 4 and 8 weeks. SF also attenuated glomerulosclerosis and tubulointerstitial injury. Moreover, several different approaches confirmed the protective effects on podocytes, explaining the attenuation of glomerulosclerosis and albuminuria observed in this study. As a possible mechanism, we found that SF attenuated renal inflammation and fibrosis in RK rats. Interestingly, von Kossa staining of the kidney revealed calcium phosphate deposition in neither RK nor RK + SF rats; however, plasma levels of calciprotein particles were significantly reduced by SF. These data indicate that latent positive phosphate balance accelerates CKD progression from early stages, even when overt ectopic calcification is absent.

Original languageEnglish (US)
Article number1732
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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    Nemoto, Y., Kumagai, T., Ishizawa, K., Miura, Y., Shiraishi, T., Morimoto, C., Sakai, K., Omizo, H., Yamazaki, O., Tamura, Y., Fujigaki, Y., Kawachi, H., Kuro-o, M., Uchida, S., & Shibata, S. (2019). Phosphate binding by sucroferric oxyhydroxide ameliorates renal injury in the remnant kidney model. Scientific reports, 9(1), [1732]. https://doi.org/10.1038/s41598-018-38389-3