The Importance of Phosphate Control in Chronic Kidney Disease

Abstract

A series of problems including osteopathy, abnormal serum data, and vascular calcification associated with chronic kidney disease (CKD) are now collectively called CKD-mineral bone disease (CKD-MBD). The pathophysiology of CKD-MBD is becoming clear with the emerging of αKlotho, originally identified as a progeria-causing protein, and bone-derived phosphaturic fibroblast growth factor 23 (FGF23) as associated factors. Meanwhile, compared with calcium and parathyroid hormone, which have long been linked with CKD-MBD, phosphate is now attracting more attention because of its association with complications and outcomes. Incidentally, as the pivotal roles of FGF23 and αKlotho in phosphate metabolism have been unveiled, how phosphate metabolism and hyperphosphatemia are involved in CKD-MBD and how they can be clinically treated have become of great interest. Thus, the aim of this review is reconsider CKD-MBD from the viewpoint of phosphorus, its involvement in the pathophysiology, causing complications, therapeutic approach based on the clinical evidence, and clarifying the importance of phosphorus management.

Reduced White Matter Integrity in Patients With End-Stage and Non-end-Stage Chronic Kidney Disease: A Tract-Based Spatial Statistics Study

“…This suggests an association between phosphate and WM abnormalities; however, little is known about the mechanism. When renal function is impaired, an increase in phosphate will cause the secretion of PTH but reduce the active form of vitamin D, which will induce secondary hyperparathyroidism (Tsuchiya and Akihisa, 2021). However, high PTH can affect the neurotransmission of the central nervous system and induce neurotoxicity (Wilmskoetter et al, 2019).…”

Use of Micro-CT Imaging to Assess Ventral Mandibular Cortical Thickness and Volume in an Experimental Rodent Model With Chronic High-Phosphorus Intake

“…Although phosphorus is an essential nutrient, in excess it could be linked to tissue damage by a variety of mechanisms involved in the endocrine regulation of extracellular phosphate, specifically the secretion and action of fibroblast growth factor 23 and parathyroid hormone. Disordered regulation of these hormones by high dietary phosphorus may be the key factor contributing to renal failure, cardiovascular disease, and osteoporosis ( 29 , 30 ). It is why the authors propose a degu as an animal model of phosphate metabolism disturbances.…”

The Emerging Role of Nutraceuticals in Cardiovascular Calcification: Evidence from Preclinical and Clinical Studies

“…In fact, in CKD patients, a dysregulated mineral metabolism, the loss of calcification inhibitors (including MGP, fetuin-A, pyrophosphate), and the activation of inflammatory pathways contribute to the development and progression of vascular calcification [ 22 ]. Moreover, the renal function impairment and the consequently reduced excretion of phosphate lead to hyperphosphatemia, a condition that favors mineral deposition in both vascular walls and the aortic valve and the phenotypic switch of VSMCs [ 23 ]. Phosphate absorption and excretion also depend on a network involving calcium, vitamin D, and parathyroid hormone (PTH), factors that are dysregulated in pathological conditions like CKD [ 22 ].…”