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.

Keywords: CKD-MBD; FGF23; aKlotho; phosphate-binder.

Figure 1

Representative sections immunohistochemically stained for α-SMA in the renal tubules in the reduced Klotho expression mice treated by unilateral ureteral obstruction. Renal fibrosis was induced by unilateral ureteral obstruction (UUO) in mice with reduced αKlotho expression αkl (+/−) mice and compared them with wild-type mice. The UUO kidneys from αkl (+/−) mice expressed significantly higher levels of fibrosis marker, α-smooth muscle actin (α-SMA), than those from wild-type αkl (+/+) mice. Adapted from reference [29].

Figure 2

Changes in Klotho protein, FGF-23, PTH, 1,25(OH)2D3, and phosphate as CKD progresses. When Klotho expression first decreases, FGF-23 increases, lowering circulating 1,25(OH)2D3, which depresses Klotho expression further and increases PTH expression. Increased PTH induces further FGF-23 increases, causing large decreases in 1,25(OH)2D3 and large increases in PTH. This cycle results in hyperphosphatemia in late stages of CKD. CKD, chronic kidney disease; FGF-23, fibroblast growth factor-23; PTH, parathyroid hormone. Adapted from reference [38].