A treatment for
hyperphosphatemia would be expected to reduce mortality rates for CKD and dialysis patients. Although rodent studies have suggested
sodium-dependent
phosphate transporter type IIb (NaPi-IIb) as a potential target for
hyperphosphatemia, NaPi-IIb selective inhibitors failed to achieve efficacy in human clinical trials. In this study, we analyzed
phosphate metabolism in rats, dogs, and monkeys to confirm the species differences. Factors related to
phosphate metabolism were measured and intestinal
phosphate absorption rate was calculated from fecal excretion in each species.
Phosphate uptake by intestinal brush border membrane vesicles (BBMV) and the
mRNA expression of NaPi-IIb, PiT-1, and PiT-2 were analyzed. In addition,
alkaline phosphatase (ALP) activity was evaluated. The intestinal
phosphate absorption rate, including
phosphate uptake by BBMV and NaPi-IIb expression, was the highest in dogs. Notably, urinary
phosphate excretion was the lowest in monkeys, and their intestinal
phosphate absorption rate was by far the lowest. Dogs and rats showed positive correlations between Vmax/Km of
phosphate uptake in BBMV and NaPi-IIb expression. Although
phosphate uptake was observed in the BBMV of monkeys, NaPi-IIb expression was not detected and ALP activity was low. This study revealed significant species differences in intestinal
phosphate absorption. NaPi-IIb contributes to intestinal
phosphate uptake in rats and dogs. However, in monkeys,
phosphate is poorly absorbed due to the slight degradation of organic
phosphate in the intestine.