Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease: An Overview

George R. Bailie, PharmD, PhD, FCCP; Shaul G. Massry, MD


Pharmacotherapy. 2005;25(12):1687-1707. 

In This Article

Soft-Tissue Calcification

The following factors may predispose to soft-tissue calcification in patients with stage 4 (GFR 15-29 ml/min/1.73 m2) or stage 5 (GFR < 15 ml/min/1.73 m2 or dialysis dependent) CKD[3]:

  • Hyperphosphatemia

  • Serum calcium-phosphorus product greater than 55 mg2/dl2

  • Secondary hyperparathyroidism

  • Local tissue injury

  • Local tissue alkalosis

  • Removal of calcification inhibitors by dialysis

  • Excessive calcium intake

    • Dietary

    • Dialysate

    • Calcium-containing phosphorus-binding agents

    • Calcium supplements


An increase in the serum calcium-phosphorus product (determined by multiplication of the values of corrected serum calcium and serum phosphorus concentrations) is probably the most important pathogenetic factor. The rate of soft-tissue calcification is high when the calcium-phosphorus product exceeds 70 mg2/dl2, whereas soft-tissue calcification is uncommon when the calcium-phosphorus product is below 50 mg2/dl2. Current recommendations are to maintain the product below 55 mg2/dl2. Hyperphosphatemia by itself, through an active process, leads to vascular calcification. Phosphorus may enter the smooth muscle cells of blood vessels. There, phosphorus may alter the phenotype of smooth muscle cells, causing them to change into osteoblasts (bone-laying cells). This transition starts the process of blood vessel calcification.

Soft-tissue calcification is a serious problem for patients with CKD. Calcification may be localized in arteries, eyes, visceral organs, and skin, as well as around joints. Uremic patients are more prone to vascular calcification because of the increased prevalence of hypertension and a propensity to accelerated atherosclerosis. Vascular calcification may involve almost every artery and may be extensive. Calcification of coronary arteries is associated with increased cardiovascular mortality in patients with stage 5 CKD.