The true cost of phosphate control in chronic kidney disease.

Abstract

The loss of kidney function entails the development of a positive phosphate balance. The burden of addressing elevated phosphate levels is high. Both parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) are increased to promote phosphaturia, thereby preventing the rise in serum phosphate. However, if the phosphate load is excessive, the corresponding phosphaturia is maximal, kidney function deteriorates and hyperphosphataemia becomes clinically evident in advanced stages of chronic kidney disease (CKD). In addition to its role in CKD progression, hyperphosphataemia has been linked to a multitude of adverse outcomes, including overt inflammation, vascular calcifications, endothelial dysfunction, cardiovascular disease, renal osteodystrophy and secondary hyperparathyroidism. Collectively, these factors contribute to the markedly elevated mortality rates observed among individuals with CKD. Furthermore, hyperphosphataemia has been identified as a significant contributor to the development of inflammatory processes, oxidative stress and fibrosis, which underlie the aetiology of numerous comorbidities. Additionally, elevated levels of PTH and FGF23 have been demonstrated to independently induce organ and tissue injury, which is associated with poor outcomes in CKD. This article provides a concise overview of the current understanding of phosphate handling by the kidney in the context of CKD. It outlines the detrimental effects of phosphate on various organs and the mechanisms through which it contributes to CKD progression. Additionally, we discuss the tools available for clinicians to identify patients at risk of an excessive phosphate load.