Abstract: TH-PO1057

Regulation of Intestinal Phosphate Transport in a Rat Model of CKD

Session Information

Category: Mineral Disease

  • 1201 Mineral Disease: Ca/Mg/PO4

Authors

  • Myakala, Komuraiah, University of Colorado, Aurora, Colorado, United States
  • Dobrinskikh, Evgenia, University of Colorado, Denver, Aurora, Colorado, United States
  • Sutherland, Eileen Marie, Uniiversity of Colorado, Denver, Colorado, United States
  • Levi, Moshe, University of Colorado Denver, Aurora, Colorado, United States
Background


In chronic kidney disease (CKD) hyperphosphatemia is a common occurrence and plays important roles in cardiovascular and bone disease. The mechanisms however still remain unknown and the role of intestinal phosphate (Pi) transport is subject of ongoing debate.

Methods

We studied regulation of intestinal phosphate transport in a model of 5/6 nephrectomy (Nx) induced CKD in the rat fed a relatively high Pi diet (1.5% Pi, 0.6% Ca).

Results


Male rats with 5/6 Nx had a marked increase in serum BUN (37.7 ± 2.0 vs. 150.5 ± 29.8 mg/dl in sham control, p<0.02), serum creatinine (0.5 ± 0.06 vs. 1.65 ± 0.23 mg/dl in sham control, p<0.008), and serum Pi (7.48 ± 0.85 vs. 18.19 ± 1.84 mg/dl in sham control, p<0.001). We isolated apical brush border membrane vesicles (BBMV) from the duodenum and the jejunum and studied sodium gradient dependent Pi (Na+/Pi) cotransport as a function of pH. Across every single pH studied, including 5.5, 6.0, 6.5, 7.0, and 7.5 Na+/Pi transport activity was increased in BBM from 5/6 Nx rats. This was associated with a 2-fold increase in NaPi-2b protein abundance in the duodenum and a1.4-fold increase in NaPi-2b protein abundance in the jejunum. To determine if there are sex-dependent differences in CKD and intestinal Na+/Pi transport, we also studied in parallel female rats with 5/6 Nx. We found that female rats with 5/6 Nx also had a marked increase in serum Pi (4.75 ± 0.39 vs. 10.7 ± 1.24 mg/dl in sham control, p<0.003). In addition, there were marked increases in intestinal Na+/Pi transport activity paralleled by increases in NaPi-2b protein abundance.

Conclusion

Our study therefore indicates that in both male and female rats with CKD, the hyperphosphatemia is mediated by increased intestinal Na//Pi transport activity and increased NaPi-2b protein expression.

Funding

  • NIDDK Support