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Abstract: SA-OR101

Dietary Phosphate Restriction Attenuates Renal Cystic Disease in pcy/pcy Mice

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Authors

  • Stubbs, Jason R., University of Kansas Medical Center, Kansas City, Kansas, United States
  • Johnson, Cassandra R., University of Kansas Medical Center, Kansas City, Kansas, United States
  • Omede, Ogorchukwu Faith, University of Kansas Medical Center, Kansas City, Kansas, United States
  • Daniel, Emily A., University of Kansas Medical Center, Kansas City, Kansas, United States
  • Wallace, Darren P., University of Kansas Medical Center, Kansas City, Kansas, United States
Background

Abnormalities in phosphate metabolism strongly predict future development and progression of chronic kidney disease (CKD); however, the mechanism remains undefined. Previously, we showed that dietary phosphate restriction reduced tubular injury in mice with glomerulonephritis. Here, we determined if dietary phosphate restriction slows renal cyst growth and fibrosis in pcy/pcy mice, a slowly progressive model of polycystic kidney disease (PKD).

Methods

At 7 weeks of age, pcy/pcy mice were randomized to receive either a control phosphate (0.54%) or low phosphate (0.02%) diet (n=10/group) until 20 weeks of age. All other major dietary constituents, including protein source and content were comparable between diets. Mice were sacrificed for measurement of kidney weight to body weight (KW/BW), cystic index (% cystic area), and renal expression of early markers of fibrosis.

Results

Pcy/pcy mice that received the low phosphate diet had a 25% lower KW/BW (low phosphate 2.9±0.3% vs. control 4.3±0.6%; P<0.001) and 30% lower cystic index (low phosphate 21.7±6.6% vs. control 31.5±4.4%; P<0.01). When examining the renal gene expression of markers of fibrosis, pcy/pcy mice fed the low phosphate diet had a 50% reduction in the expression of collagen 1a1 (P<0.05) and a 40% reduction in the expression a-smooth muscle actin (P<0.01).

Conclusion

Dietary phosphate restriction attenuates PKD progression and renal gene expression for early markers of fibrosis in pcy/pcy mice.

Effect of dietary phosphate on cyst burden in pcy/pcy mice. (A) Cross-sections of kidneys from 20 week-old pcy/pcy mice receiving either a control diet or low phosphate diet. (B) Kidney cystic index scoring from pcy/pcy mice receiving either control or low phosphate diet. **P<0.01

Funding

  • NIDDK Support