Phosphorus Intake and Outcomes in Chronic Kidney Disease: Cardiovascular, Skeletal, and Mortality Risks

Chronic kidney disease (CKD) is characterized by progressive disturbances in phosphorus homeostasis that contribute to the development of cardiovascular disease and CKD-mineral and bone disorder. Because dietary phosphorus intake is frequently excessive in Western diets, phosphorus restriction has emerged as a potential strategy to improve clinical outcomes in CKD. This review summarizes the current evidence linking dietary phosphorus intake with cardiovascular disease, mortality, and bone health in CKD. Experimental studies consistently demonstrate that phosphorus excess promotes vascular calcification, endothelial dysfunction, cardiac hypertrophy, inflammation, and increased fibroblast growth factor 23 secretion, providing strong mechanistic support for a causal role in cardiovascular injury. However, observational studies examining dietary phosphorus intake or oral phosphorus binder use and cardiovascular outcomes have yielded inconsistent findings, likely reflecting limitations in dietary assessment, differences in phosphorus bioavailability, and residual confounding by dietary protein intake, nutritional status, and other factors. By contrast, evidence linking dietary phosphorus intake with bone disease is more consistent. Controlled feeding studies demonstrate that higher phosphorus intake increases parathyroid hormone concentrations, whereas reducing total phosphorus intake or limiting phosphorus-containing food additives lowers parathyroid hormone and fibroblast growth factor 23 concentrations, often without changes in serum phosphorus. Collectively, current evidence suggests that therapeutic strategies focusing on phosphorus source and bioavailability may be more important than those targeting total phosphorus intake alone for optimizing cardiovascular and bone health in CKD. Future clinical trials are needed to determine whether reducing highly absorbable inorganic phosphorus additives improves cardiovascular, skeletal, and survival outcomes in patients with CKD.