The Dietary Fiber Inulin Slows Progression of Chronic Kidney Disease–Mineral Bone Disorder (CKD-MBD) in a Rat Model of CKD

Abstract

Chronic kidney disease (CKD)–mineral bone disorder (CKD‐MBD) leads to fractures and cardiovascular disease. Observational studies suggest beneficial effects of dietary fiber on both bone and cardiovascular outcomes, but the effect of fiber on CKD‐MBD is unknown. To determine the effect of fiber on CKD‐MBD, we fed the Cy/+ rat with progressive CKD a casein‐based diet of 0.7% phosphate with 10% inulin (fermentable fiber) or cellulose (non‐fermentable fiber) from 22 weeks to either 30 or 32 weeks of age (~30% and ~15% of normal kidney function; CKD 4 and 5). We assessed CKD‐MBD end points of biochemistry, bone quantity and quality, cardiovascular health, and cecal microbiota and serum gut‐derived uremic toxins. Results were analyzed by two‐way analysis of variance (ANOVA) to evaluate the main effects of CKD stage and inulin, and their interaction. The results showed that in CKD animals, inulin did not alter kidney function but reduced the increase from stage 4 to 5 in serum levels of phosphate and parathyroid hormone, but not fibroblast growth factor‐23 (FGF23). Bone turnover and cortical bone parameters were similarly improved but mechanical properties were not altered. Inulin slowed progression of aorta and cardiac calcification, left ventricular mass index, and fibrosis. To understand the mechanism, we assessed intestinal microbiota and found changes in alpha and beta diversity and significant changes in several taxa with inulin, together with a reduction in circulating gut derived uremic toxins such as indoxyl sulfate and short‐chain fatty acids. In conclusion, the addition of the fermentable fiber inulin to the diet of CKD rats led to a slowed progression of CKD‐MBD without affecting kidney function, likely mediated by changes in the gut microbiota composition and lowered gut‐derived uremic toxins.