Dietary Phosphorus in Chronic Kidney Disease: Effects of Amount, Source and Bioaccessibility on Intestinal Absorption and Health Outcomes

Abstract

Phosphorus restriction is a key component to dietary recommendations for patients with chronic kidney disease (CKD) to aid in the prevention of CKD-mineral bone disorder (CKD-MBD). However, this is challenging and burdensome to follow, leading to bouts of non-adherence. How these bouts of non-adherence affect intestinal phosphorus absorption remains unclear. In addition, other approaches to manage dietary phosphorus intake are of growing interest such as the incorporation of plant-based protein. How these new dietary approaches to manage phosphorus intake affect intestinal phosphorus absorption or other health outcomes in CKD must be determined. In this dissertation, we aimed to evaluate how dietary phosphorus amount, source, and bioaccessibility affect intestinal phosphorus absorption and health outcomes in CKD. We first sought to determine the effect of acute high dietary phosphorus intake following acclimation to a low phosphorus diet on intestinal fractional phosphorus absorption using an in vivo oral gavage technique in a rodent model of CKD. Despite finding no difference in intestinal fractional phosphorus absorption between groups, plasma phosphorus, fibroblast growth factor-23, and parathyroid hormone were all significantly higher in rats in the low to high phosphorus and high phosphorus groups compared to the low phosphorus group. These findings support continued efforts to reduce phosphorus intake in patients with CKD. We then aimed to determine phosphorus bioaccessibility of emerging plant-based protein products as a new approach to manage dietary phosphorus intake. We found that average phosphorus bioaccessibility ranged from ~32% in pulse-based beef to ~100% in pulse-based milk. Despite this large range in percent bioaccessible phosphorus, most of the plant-based protein products evaluated had lower phosphorus bioaccessibility in mg per 100g serving compared with animal-based protein products. However, how this translates in vivo is still unknown. Additionally, we undertook a systematic review to summarize the available clinical trial evidence for the effect of plant-based protein on kidney function and MBD outcomes in adults with stage 3-5 CKD not on dialysis. Overall, results for both kidney function and CKD-MBD outcomes were heterogenous and most studies were of suboptimal methodological quality. Of the included studies, a subset of five investigated a change in protein source only (i.e., animal vs plant). No change in kidney function was reported in four studies, while one study, of longer duration, reported a decrease. Further, of the CKD-MBD outcomes only one short term study reported lower serum phosphorus following a vegetarian diet. While our results from the study of intestinal phosphorus absorption in rodents support continued efforts to reduce phosphorus intake in patients with CKD, it is evident that other approaches to help manage phosphorus intake in this population are required. Our findings for phosphorus bioaccessibility indicate that emerging plant-based proteins may be suitable options for patients with CKD as they offer lower phosphorus bioaccessibility compared with animal products. However, our systematic review results show that sparse data with heterogenous results are available for the effect of plant-based protein compared with animal protein on kidney function and CKD-MBD outcomes in adults with stage 3-5 CKD not on dialysis. Therefore, more research must be conducted to determine the health effects of plant-based protein consumption to manage phosphorus intake in patients with CKD.