Kidney Week

Abstract: TH-PO1034

Diet Induced Iron Deficiency Inhibits Intestinal Phosphate Absorption by a NaPi-IIb-Independent Mechanism

Session Information

• Mineral Disease: Ca/Mg/PO4
  November 02, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Mineral Disease

• 1201 Mineral Disease: Ca/Mg/PO4

Authors

• Asowata, Evans Ohenhen, University College London, London, United Kingdom

Evans Ohenhen Asowata,

• Srai, Surjit Kaila Singh, University College London, London, United Kingdom

Surjit Kaila Singh Srai,

• Unwin, Robert J., University College London, London, United Kingdom

Robert J. Unwin,

• Marks, Joanne, University College London, London, United Kingdom

Joanne Marks,

Background

Recent evidence suggests that iron-deficiency influences phosphate (Pi) homeostasis through altered transcription and processing of FGF-23 in osteocytes. In addition, older studies have provided conflicting data as to whether diet induced iron-deficiency impacts intestinal Pi absorption. We aimed to confirm if iron-deficiency alters intestinal Pi absorption, and if so, to investigate the underlying mechanisms.

Methods

Six-week old male Sprague-Dawley rats and C57Bl/6 mice were fed an iron-deficient (ID) diet (2-6 ppm iron) or control (C) diet (48 ppm iron) for 2-weeks, with both diets including 0.6% Pi. In vivo and in vitro Pi uptake experiments using a physiological Pi concentration (10mM) were used to examine changes in intestinal Pi absorption in these models. Western blotting, qPCR, and ELISAs were employed to understand the underlying mechanisms.

Results

Diet induced iron-deficiency inhibited Pi absorption in the rat duodenum in vivo (C: 6.0±0.6 vs. ID: 2.5±0.6 nmoles Pi in 1ml plasma/5cm, n=7, P<0.01), while FGF-23 and 1, 25(OH)₂D₃ levels were unaffected. In contrast, in vivo Pi absorption in the mouse ileum, which is known to be mediated predominantly by NaPi-IIb, was unaffected by iron-deficiency (C: 92.2±9.9 vs. ID: 98.3±8.5 nmoles Pi in 1ml plasma/5cm, n=6). In addition, the NaPi-IIb inhibitor, PFA (10mM), did not inhibit in vitro Pi absorption in the duodenum of control rats (C: 32.80±2.95 vs. C + PFA: 32.03±1.32 nmoles Pi/100mg, n=6), while iron-deficiency caused a significant reduction (ID: 10.04±1.21, P<0.0001, n=6), suggesting that this response is not dependent on NaPi-IIb. Interestingly, Western blotting showed that iron-deficiency significantly increased the expression of claudin 3 (C: 0.18±0.01 vs. ID: 0.37±0.07; P<0.05, n=6), as well as the apical membrane iron transporter, DMT1 (C: 0.10±0.02 vs. ID: 0.51±0.01; P<0.05, n=3).

Conclusion

We hypothesise that increased DMT1 expression may locally impact intestinal Pi absorption by a mechanism involving DMT1-induced accumulation of intracellular H⁺ in the enterocyte resulting in increased claudin 3 levels, and subsequent sealing of the tight junction to reduce paracellular Pi absorption. Understanding how diet induced iron-deficiency affects intestinal Pi absorption may identify a novel target for the management of hyperphosphataemia in CKD patients.