Abstract: TH-PO146
The Effect of Carnitine Supplementation in a Rat Model of CKD-MBD
Session Information
- CKD-MBD: Targets and Outcomes
November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 401 Bone and Mineral Metabolism: Basic
Authors
- Avin, Keith G., Indiana University–Purdue University Indianapolis, Indianapolis, Indiana, United States
- Troutman, Ashley Danielle, Indiana University–Purdue University Indianapolis, Indianapolis, Indiana, United States
- Chen, Neal X., Indiana University School of Medicine, Indianapolis, Indiana, United States
- Srinivasan, Shruthi, Indiana University School of Medicine, Indianapolis, Indiana, United States
- O'Neill, Kalisha, Indiana University School of Medicine, Indianapolis, Indiana, United States
- Biruete, Annabel, Indiana University–Purdue University Indianapolis, Indianapolis, Indiana, United States
- Moe, Sharon M., Indiana University School of Medicine, Indianapolis, Indiana, United States
Background
Carnitine affects the musculoskeletal system by shuttling fatty acids into the mitochondria for β-oxidation and adenosine triphosphate production. Lower carnitine levels are seen with primary and secondary CKD carnitine deficiency and are associated with impaired musculoskeletal health. We sought to determine if carnitine treatment can benefit CKD-MBD outcomes in CKD.
Methods
We used a slowly, progressive, naturally occurring, CKD rat model (Cy/+ rat) in these groups (n=12/gr): 1) normal littermates (NL), 2) CKD rats, 3) CKD + carnitine (250mg/kg, I.P. daily). Carnitine treatments began at 22 weeks and continued through 32 weeks of age (i.e., mild to severe CKD, respectively). At 32 weeks, the animals were terminated followed by tissue and blood collection. Data analysis included one-way ANOVA with Tukey’s test.
Results
CKD rats had lower carnitine plasma levels compared to NL (p<0.05). Carnitine-treated CKD rats had higher plasma carnitine levels when compared to CKD alone (56±25 mM vs. 20±3.5 mM; p<0.0001). Compared to NL, CKD increased blood urea nitrogen, serum creatinine, phosphorous, parathyroid hormone, intact FGF23, c-terminal FGF23 and vascular calcification (all comparisons p<0.04). CKD bone volume and tibial number were lower, while tibial spacing was higher compared to NL (all comparisons p<0.04). 10 weeks of carnitine treatment increased plasma levels of creatinine, phosphorus, PTH, intact FGF23 and c-terminal FGF23 in CKD rats (all comparisons p<0.04). Carnitine treatment had no affect on vascular calcification, but increased cortical porosity in carnitine-treated CKD rats compared to CKD alone (p<0.04).
Conclusion
Carnitine supplementation did not alter vascular calcification but negatively impacted bone-related outcomes and worsened biochemistries of CKD-MBD. The change in porosity is likely due to the increase in PTH that occurred in the CKD + carnitine animals. In summary, carnitine treatment for 10 weeks that achieved supraphysiologic levels had adverse effects on CKD-MBD, despite dosing that was tested at earlier time point in CKD, and was modest compared to other studies. Whether lower doses or shorter treatment has different effect is unknown. However, this study raises caution about the wide use of supplements containing carnitine by individuals with CKD.
Funding
- NIDDK Support