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Kidney Week

Abstract: PO1202

Wheat-Gluten Diet Attenuates Ccl2-Mediated Immune Response and Slows Polycystic Kidney Disease

Session Information

Category: Genetic Diseases of the Kidneys

  • 1001 Genetic Diseases of the Kidneys: Cystic

Authors

  • Huang, Jifeng, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Yamaguchi, Shinobu, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Hsu, Jung-Shan, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Saigusa, Takamitsu, The University of Alabama at Birmingham, Birmingham, Alabama, United States

Group or Team Name

  • Department of Medicine, Division of Nephrology
Background

Disease severity of autosomal-dominant polycystic kidney disease (ADPKD) is highly variable, even among families with the same gene mutation. A high protein diet is a well-recognized ADPKD progression-accelerating factor. Dietary protein composition is important, as pre-clinical studies have shown a soy protein-based diet slows kidney cyst formation in rodent PKD models. Recruitment of macrophages in the kidney are known to promote cystogenesis in PKD. We hypothesize that type of protein in the diet may serve as a potential environmental stimulant to immune response and cyst growth.

Methods

Using tamoxifen-inducible Pkd1-global knockout mice, we fed the mice with either a high casein-protein (animal-based protein: 60%), a low casein-protein (6%) or a high wheat-gluten (plant-based protein: 60%) for a total of 1 week or 6 weeks. Some mice fed a high casein protein diet were treated with liposomal clodronate or saline for a total of 5 weeks. Mice were euthanized and kidney cyst area, number of macrophages and chemokine/cytokine levels were measured.

Results

Pkd1-knockout mice fed a high casein diet increased the number of kidney macrophages, expression of macrophage-recruiting chemokine Ccl2 (but not chemokines Csf1 or Ccl5), pro-inflammatory cytokine (Il6, Tnf-a) and accelerated cyst growth compared to counterparts fed an iso-caloric high wheat-gluten (WG) diet or a low casein protein diet. We found that in very early stages during dietary casein load (1 week after diet modification), cyst expansion precedes macrophage recruitment in the kidney, indicating that diet per se triggers early cyst growth rather than as a consequence of macrophage recruitment and inflammation. High casein protein diet fed Pkd1-knockout mice treated with liposomal clodronate, resulted in decreased number of macrophages, cytokine and fewer cysts.

Conclusion

Wheat-gluten diet fed Pkd1-knockout mice resulted in decreased the number of macrophages, suppressed levels of kidney Ccl2, but not Csf1 or Ccl5, and slowed cyst growth compared to counterparts fed an isocaloric casein based diet. Dietary protein modification may suppress immune response and cyst growth in PKD.

Funding

  • NIDDK Support