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Kidney Week

Abstract: PO1557

Cyst-Lumen Renal Stones in Mice Compound Heterozygous for Hypomorphic Pkd1V and Pkd1RC Alleles

Session Information

Category: Genetic Diseases of the Kidneys

  • 1001 Genetic Diseases of the Kidneys: Cystic

Authors

  • Parnell, Stephen C., University of Kansas Medical Center, Kansas City, Kansas, United States
  • Riddle, Heather A.L., University of Kansas Medical Center, Kansas City, Kansas, United States
  • Zhang, Shiqin, University of Kansas Medical Center, Kansas City, Kansas, United States
  • Qian, Feng, University of Maryland School of Medicine, Baltimore, Maryland, United States
  • Williams, James C., Indiana Uniersity School of Medicine, Indianapolis, Indiana, United States
  • Stubbs, Jason R., University of Kansas Medical Center, Kansas City, Kansas, United States
  • Rowe, Peter S. N., University of Kansas Medical Center, Kansas City, Kansas, United States
Background

Autosomal dominant polycystic kidney disease (ADPKD) patients exhibit a ~2.5-fold higher propensity for renal stone formation compared to that of the general population. However, there are no good mouse models for the analysis of stone formation in ADPKD. We previously reported the presence of cortical renal stones in cystic mice compound heterozygous for hypomorphic alleles Pkd1V and Pkd1RC (Parnell et al. 2018 J Am Soc Nephrol 29:295). In this present study, the composition and location of the renal stones in this PKD model were determined.

Methods

Pkd1V and Pkd1RC mice on a C57 background were crossed to produce cystic Pkd1V/RC mice. Mice were sacrificed at 3-26 weeks and their kidneys analyzed by Alizarin Red and von Kossa staining. Individual stones were microdissected from cysts and analyzed by μCT and infrared spectroscopic analysis to determine their composition.

Results

Although Pkd1V/RC mice were noticeably cystic by 3-weeks of age, stone formation was not obvious until ~13-weeks. Histological sections from 13- and 26-week old mice had regions that stained positive by Alizarin Red and von Kossa in a generally overlapping pattern. In contrast, there were no obvious staining patterns by Alizarin Red or von Kossa in kidneys from 3-week old mice. When kidneys were dissected it became evident that the stones were found almost exclusively within the lumens of cysts (see microdissected cyst with internal stone in Figure 1). μCT and infrared spectroscopic analysis confirmed that dissected stones were comprised of calcium phosphate in the mineral form of apatite, and also rich in protein.

Conclusion

Pkd1V/RC mice develop mineralized stone deposits comprised of apatite and protein within the renal cystic lumen. To our knowledge this is the first known instance of renal stones in a mouse model of ADPKD.

Funding

  • NIDDK Support