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Abstract: FR-PO513

Effect of Ovariectomy on the Progression of CKD-Mineral Bone Disorder (CKD-MBD) in Cy/+ Rats

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Authors

  • Vorland, Colby, Purdue University, West Lafayette, Indiana, United States
  • Lachcik, Pamela, Purdue University, West Lafayette, Indiana, United States
  • Nelson, Courtney N., Purdue University, West Lafayette, Indiana, United States
  • Chen, Neal X., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Moe, Sharon M., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Hill Gallant, Kathleen M., Purdue University, West Lafayette, Indiana, United States
Background

There is increasing interest in sex as a biologic variable, yet studies have generally not examined the role of sex in the pathogenesis of CKD-MBD despite experimental and epidemiological evidence suggesting that estrogen is protective to kidney function and bone and thus CKD-MBD. In the Cy/+ rat model of CKD-MBD, a spontaneous genetic mutation causes progressive kidney function decline in males prior to 20 weeks of age, but kidney function is maintained in females past 80 weeks of age making it impractical to study these females as a model of CKD. Therefore, ovariectomy to mimic a post-menopausal state may accelerate the initiation of the CKD-MBD phenotype and enable the use of female Cy/+ rats in research.

Methods

Sixteen female Cy/+ rats were randomized to either ovariectomy (OVX) (n=8) or sham surgery (n=8) at 15 weeks of age. A casein-based diet was initiated at 24 weeks of age to promote kidney function decline as is done in studies with male Cy/+ rats. Blood was sampled at 10, 20, 25, 30, and 35 weeks of age, and analyzed for BUN, plasma phosphorus, and plasma calcium.

Results

Data collected on all n=16 through 25 weeks show that OVX rats have higher body weights (p<0.0001) (and lower uterine weights for n=4 that completed the 35 weeks of the study) confirming the success of the OVX procedure. Plasma phosphorus decreased over time in both groups (p<0.0001), but was not different between groups (p=0.46). Plasma calcium was not different between groups (p=0.38) and did not change over time (p=0.57). Plasma BUN decreased slightly over time in both groups (p<0.01) but remained in normal ranges, and there is no difference between OVX and sham (p=0.23). In n=2 OVX and n=2 sham that have completed the 35 weeks of the study, preliminary analysis shows no appreciable difference in BUN, phosphorus, or calcium between groups.

Conclusion

Analyses will continue through 35 weeks, however at 25 weeks of age, there is currently no indication that OVX accelerates kidney function decline in female Cy/+ rats. This is in contrast to Cy/+ male rats which can be phenotyped based on elevated BUN as early as 10 weeks of age, and by 25 weeks of age exhibit a ~50% reduction in kidney function (Moe et al. 2011).

Funding

  • NIDDK Support