Kidney Week

Abstract: FR-PO490

Significant Differences Exist in Intestinal Phosphate Absorption Between Species

Session Information

• Bone and Mineral Metabolism: Basic
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Bone and Mineral Metabolism

• 401 Bone and Mineral Metabolism: Basic

Authors

• Ichida, Yasuhiro, Chugai Pharmaceutical Co. Ltd., Gotemba, Shizuoka, Japan

Yasuhiro Ichida,

• Hosokawa, Naoto, Chugai Pharmaceutical Co. Ltd., Gotemba, Shizuoka, Japan

Naoto Hosokawa,

• Takemoto, Ryushi, Chugai Research Institute for Medical Science, Inc., Gotemba, Shizuoka, Japan

Ryushi Takemoto,

• Koike, Takafumi, Chugai Research Institute for Medical Science, Inc., Gotemba, Shizuoka, Japan

Takafumi Koike,

• Nakatogawa, Tasuku, Chugai Research Institute for Medical Science, Inc., Gotemba, Shizuoka, Japan

Tasuku Nakatogawa,

• Hiranuma, Mayumi, Chugai Research Institute for Medical Science, Inc., Gotemba, Shizuoka, Japan

Mayumi Hiranuma,

• Arakawa, Hitoshi, Chugai Research Institute for Medical Science, Inc., Gotemba, Shizuoka, Japan

Hitoshi Arakawa,

• Miura, Yukihito, Chugai Research Institute for Medical Science, Inc., Gotemba, Shizuoka, Japan

Yukihito Miura,

• Azabu, Hiroko, Chugai Research Institute for Medical Science, Inc., Gotemba, Shizuoka, Japan

Hiroko Azabu,

• Ohtomo, Shuichi, Chugai Pharmaceutical Co. Ltd., Gotemba, Shizuoka, Japan

Shuichi Ohtomo,

• Horiba, Naoshi, Chugai Pharmaceutical Co. Ltd., Gotemba, Shizuoka, Japan

Naoshi Horiba,

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.