ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: FR-PO490

Significant Differences Exist in Intestinal Phosphate Absorption Between Species

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Authors

  • Ichida, Yasuhiro, Chugai Pharmaceutical Co. Ltd., Gotemba, Shizuoka, Japan
  • Hosokawa, Naoto, Chugai Pharmaceutical Co. Ltd., Gotemba, Shizuoka, Japan
  • Takemoto, Ryushi, Chugai Research Institute for Medical Science, Inc., Gotemba, Shizuoka, Japan
  • Koike, Takafumi, Chugai Research Institute for Medical Science, Inc., Gotemba, Shizuoka, Japan
  • Nakatogawa, Tasuku, Chugai Research Institute for Medical Science, Inc., Gotemba, Shizuoka, Japan
  • Hiranuma, Mayumi, Chugai Research Institute for Medical Science, Inc., Gotemba, Shizuoka, Japan
  • Arakawa, Hitoshi, Chugai Research Institute for Medical Science, Inc., Gotemba, Shizuoka, Japan
  • Miura, Yukihito, Chugai Research Institute for Medical Science, Inc., Gotemba, Shizuoka, Japan
  • Azabu, Hiroko, Chugai Research Institute for Medical Science, Inc., Gotemba, Shizuoka, Japan
  • Ohtomo, Shuichi, Chugai Pharmaceutical Co. Ltd., Gotemba, Shizuoka, Japan
  • Horiba, Naoshi, Chugai Pharmaceutical Co. Ltd., Gotemba, Shizuoka, Japan
Background

The efficacy of a NaPi-IIb specific inhibitor was recently reported to be different between rat and human. In addition, intestinal phosphate absorption was previously reported to be different between rat and mouse. This study analyzed intestinal phosphate absorption in dog, monkey, and rat and also investigated the concentrations of phosphate and related hormones in serum. The results showed significant differences in the intestinal phosphate absorption between the three species.

Methods

Fecal and urinary phosphate excretion were compared in dog, monkey, and rat after paired feeding. Phosphate uptake by intestinal brush border membrane vesicles (BBMV) and the mRNA expression of NaPi-IIb, PiT-1, and PiT-2 were also evaluated in duodenum, jejunum, and ileum of each species. In addition, the ALP activity in each intestinal segment and the concentration of serum phosphate and FGF23 were measured.

Results

The intestinal phosphate absorption rate, as calculated from food intake and fecal excretion, was highest in dog out of the three species, as were urinary fractional excretion of phosphate and serum concentration of FGF23. Accordingly, phosphate uptake with BBMV and mRNA expression of NaPi-IIb were also highest in dog. Surprisingly, urinary phosphate excretion was lowest in monkey, and the intestinal phosphate absorption rate in monkey was by far the lowest out of the three species. Dog and rat showed positive correlations between phosphate uptake with BBMV and mRNA expression of NaPi-IIb in each intestinal segment. Although phosphate uptake in BBMV was high in monkey, mRNA expression of NaPi-IIb was not detected in any of the intestinal segments, and intestinal ALP activity was low.

Conclusion

These results suggest that, whereas NaPi-IIb is the major contributor to intestinal phosphate absorption in dog and rat, monkey phosphate degrades only slightly in the intestine, and its contribution to intestinal phosphate absorption might be through a sodium-dependent phosphate transporter other than NaPi-IIb. In conclusion, there are significant differences in intestinal phosphate absorption between dog, monkey, and rat. Further analysis is needed to elucidate the phosphate absorption in human.