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Kidney Week

Abstract: PO1249

Restricted Feeding Diet Overrides the Cyst Promoting Effect of Cisplatin-Induced Renal Injury in Both Ift88 and Pkd2 Mutant Mouse Models

Session Information

Category: Genetic Diseases of the Kidneys

  • 1001 Genetic Diseases of the Kidneys: Cystic

Authors

  • Li, Zhang, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Cherakara, Sreelakshmi, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Haycraft, Courtney J., The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Yoder, Bradley K., The University of Alabama at Birmingham, Birmingham, Alabama, United States
Background

Multiple renal cystic diseases, including PKD, are caused by dysfunction of the primary cilium. Links between cilia dysfunction, cyst formation, and renal injuries have been reported with evidence showing that injury exacerbated the rate of cyst formation in kidney. In addition, dietary restriction has been reported to ameliorate cyst growth in several PKD animal models. Here we evaluate the effects of both renal injury and dietary restriction on cyst formation in two different cilia-mutant mouse models.

Methods

To test the effect of renal injury on cyst formation, we established an alternative approach to induce chronic renal injury by utilizing a low-dose repeated cisplatin treatment (5.0mg/kg; IP; once a week for 4 wks). To evaluate the impact of dietary restriction and renal injury on cyst formation, adult induced conditional Ift88 and Pkd2 mutant mice were utilized. The study design including cisplatin treatment along with 85 % dietary intakes are shown in Figure 1. Mice were euthanized at 5 wks post last cisplatin injection for analysis. Multiple features including renal injury, proliferation, fibrosis, macrophage accumulation, and cystic index were analyzed.

Results

Low-dose repeated cisplatin treatment resulted in increased Kim1 expression in both Ift88 and Pkd2 mutant mice compared to controls. Analysis of the cystic phenotype showed that there was a significant increase in cyst formation in mutant mice after cisplatin comparing to saline-treated group and the location of cysts corresponded to the injured regions. Interestingly, the rapid cyst formation in cisplatin-treated kidneys was ameliorated when the mice were on the restricted diet (Figure 1). More importantly, kidneys from mice with restricted feeding displayed decreased levels of proliferation, fibrosis and macrophage accumulation around the cystic area.

Conclusion

These data show that low-dose repeated cisplatin treatment could be used as an alternative approach to IRI to accelerate cyst formation in in both ift88 and pkd2 mutant models. More importantly, it suggests that cyst progression associated with injury in cystic kidney disorders could be ameliorated through dietary interventions.

Funding

  • NIDDK Support