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Abstract: FR-PO244

Divergent Injury Effects of Cisplatin Treatment on Promoting Cyst Formation in Adult Pkd2 Mutant Mouse Model

Session Information

Category: Genetic Diseases of the Kidneys

  • 1101 Genetic Diseases of the Kidneys: Cystic

Authors

  • Li, Zhang, The University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States
  • Cherakara, Sreelakshmi, The University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States
  • Andersen, Reagan S., The University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States
  • Yoder, Bradley K., The University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States
Background

Cisplatin is a widely used antitumor drug with severe nephrotoxic side effects, which could result in acute or chronic kidney injury depending on the dosage. Links between cyst formation and renal injuries have been reported in multiple PKD animal models, but the effect of cisplatin-induced injury on cyst formation has not been investigated. Here we evaluate the effect of two different regimens of cisplatin treatment on renal injury and cyst formation in Pkd2 mutant mouse models.

Methods

Adult-induced Pkd2 mutant mice were treated with either a single dose (9 mg/kg) or four weekly doses (5 mg/kg each) of cisplatin by IP injection to induce acute or chronic renal injury models, respectively (Experimental Design in Figure). Mice were euthanized 8 weeks after initial cisplatin treatment for analysis. Renal injury (SOX9 and KIM1), proliferation (Ki67), apoptosis, fibrosis, macrophage accumulation, and cystic index were analyzed using, immunofluorescence, FACS and histology approaches.

Results

Both cisplatin treatment regimens accelerate cyst formation in mutant mice relative to saline-treated controls. The cystic index is increased in mutant mice with acute injury model compared to chronic injury model (Figure). More important, kidneys from mice receiving a single cisplatin treatment had less fibrosis and macrophage accumulation but increased cell proliferation compared to the multiple cisplatin treatment group. The injury response between the two cisplatin treatment approaches is currently being investigated.

Conclusion

These data show that cisplatin treatment caused renal injury and enhanced cyst formation in Pkd2 mutant kidney, and that the cisplatin protocol could be used as an alternative injury method to accelerate cyst formation in cystic kidney disease models. Additionally, these data suggest that acute and chronic injury models have distinct effects on cystic index, fibrosis, and cell proliferation.

Cisplatin-induced injury accelerates cyst formation in Pkd2 mutant kidney

Funding

  • NIDDK Support