A Role of Intestinal Alkaline Phosphatase 3 (Akp3) in Inorganic Phosphate Homeostasis

• Published in: Kidney & blood pressure research Vol. 43; no. 5; pp. 1409 - 1424
• Main Authors: Sasaki, Shohei, Segawa, Hiroko, Hanazaki, Ai, Kirino, Ruri, Fujii, Toru, Ikuta, Kayo, Noguchi, Miwa, Sasaki, Sumire, Koike, Megumi, Tanifuji, Kazuya, Shiozaki, Yuji, Kaneko, Ichiro, Tatsumi, Sawako, Shimohata, Takaaki, Kawai, Yoshichika, Narisawa, Sonoko, Millán, José Luis, Miyamoto, Ken-ichi
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2018; Karger Publishers
• Subjects: Adenine; Alkaline phosphatase; Alkaline Phosphatase - genetics; Alkaline Phosphatase - physiology; Animals; Biological Transport; Calcitriol; Calcium; Calcium ions; CKD-MBD; Diet; Disease Models, Animal; Enzyme-linked immunosorbent assay; Failure; Fibroblast growth factor 23; Gene deletion; Growth factors; Homeostasis; Hyperphosphatemia; In vivo methods and tests; Intestinal Mucosa - metabolism; Intestine; Kidney diseases; Kinases; Membrane vesicles; Menopause; Metabolism; Mice; Mice, Knockout; Original Paper; Parathyroid; Parathyroid hormone; Phosphatase; Phosphate transporter; Phosphates; Phosphates - blood; Phosphates - metabolism; Phosphorus; Protein transport; Renal failure; Renal Insufficiency - metabolism; Small intestine; Sodium; Sodium-Phosphate Cotransporter Proteins, Type IIb - metabolism; Transport; Urine; Vitamin D; Japan; Hyperphosphatemia; Phosphate transporter; CKD-MBD
• ISSN: 1420-4096; 1423-0143
• DOI: 10.1159/000493379

Background/Aims: Hyperphosphatemia is a serious complication of late-stage chronic kidney disease (CKD). Intestinal inorganic phosphate (Pi) handling plays an important role in Pi homeostasis in CKD. We investigated whether intestinal alkaline phosphatase 3 (Akp3), the enzyme that hydrolyzes dietary Pi compounds, is a target for the treatment of hyperphosphatemia in CKD. Methods: We investigated Pi homeostasis in Akp3 knockout mice (Akp3 -/- ). We also studied the progression of renal failure in an Akp3 -/- mouse adenine treated renal failure model. Plasma, fecal, and urinary Pi and Ca concentration were measured with commercially available kit, and plasma fibroblast growth factor 23, parathyroid hormone, and 1,25(OH) 2 D 3 concentration were measured with ELISA. Brush border membrane vesicles were prepared from mouse intestine using the Ca 2+ precipitation method and used for Pi transport activity and alkaline phosphatase activity. In vivo intestinal Pi absorption was measured with oral 32 P administration. Results: Akp3 -/- mice exhibited reduced intestinal type II sodium-dependent Pi transporter (Npt2b) protein levels and Na-dependent Pi co-transport activity. In addition, plasma active vitamin D levels were significantly increased in Akp3 -/- mice compared with wild-type animals. In the adenine-induced renal failure model, Akp3 gene deletion suppressed hyperphosphatemia. Conclusion: The present findings indicate that intestinal Akp3 deletion affects Na + -dependent Pi transport in the small intestine. In the adenine-induced renal failure model, Akp3 is predicted to be a factor contributing to suppression of the plasma Pi concentration.