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Abstract: FR-OR01

The Effect of a Fermentable Dietary Fiber Inulin on a Rat Model of CKD-MBD

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Authors

  • Chen, Neal X., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • O'Neill, Kalisha, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Srinivasan, Shruthi, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Metzger, Corinne E., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Fallen, Paul B., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Biruete, Annabel, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Evenepoel, Pieter, Nephrology and Renal Transplantation Research Group, Leuven, Herestraat 49, Belgium
  • Allen, Matthew R., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Moe, Sharon M., Indiana University School of Medicine, Indianapolis, Indiana, United States
Background

Human studies have suggested that a diet rich in fermentable dietary fiber may prevent the progression of chronic kidney disease and its associated complications by altering gut microbiome and decreasing uremic toxins. The goal of this study is to investigate if the fermentable fiber inulin supplement will improve CKD-MBD.

Methods

We treated a naturally occurring model of CKD-MBD, the Cy/+ rat, with a casein-based diet supplemented with or without the fermentable fiber 10% inulin for 10 weeks, starting at 22 weeks (~CKD stage 3b) with euthanization at 32 wk (~15% of normal GFR). Normal littermates (NL) were used as control. Blood biochemistry, cardiovascular parameters and bone quantity and turnover were assessed.

Results

CKD rats had the expected elevations of blood creatinine, phosphorus, PTH, fibroblast growth factor 23 (FGF23) and oxidative stress marker 8-OHdG compared to NL. The CKD with inulin treatment compared to CKD without inulin had similar kidney function, but reduced levels of plasma phosphorus by 23% (p<0.001), PTH by 65% (p<0.003) and 8-OHdG by 22% (p<0.01). CKD rats had elevated serum levels of uremic toxin indoxyl sulfate (IS) and p-cresyl sulfate (PS) and inulin treatment significantly decreased IS levels by 54% (p<0.001) and PS levels by 80% (p<0.02). Inulin treatment also improved cardiovascular parameters in CKD rats by reducing aorta calcification by 28%, heart calcification by 80% and left ventricular mass by 17%. In the skeleton, CKD rats had increased cortical porosity and reduced cortical thickness and area compared to NL and inulin treatment in CKD rats normalized these parameters (P<0.01). Furthermore, inulin treatment decreased trabecular osteoclast surfaces by 37% in CKD rats. However, inulin treatment did not improve bone mechanics in CKD rats.

Conclusion

These results suggested that the fermentable dietary fiber inulin had a beneficial effect on CKD-MBD by reducing cardiovascular disease, cortical porosity, and osteoclasts although there was no effect on bone mechanics. These data suggest that changes in gut microbiota and/or uremic toxins may play a role in the severity of CKD-MBD and may justify a concerted effort to increase fermentable fiber in the diet of patients.