Phosphate binders, vitamin D and calcimimetics in the management of chronic kidney disease-mineral bone disorders (CKD-MBD) in children

Abstract

In order to minimize complications on the skeleton and to prevent extraskeletal calcifications, the specific aims of the management of chronic kidney disease mineral and bone disorder (CKD-MBD) are to maintain blood levels of serum calcium and phosphorus as close to the normal range as possible, thereby maintaining serum parathyroid hormone (PTH) at levels appropriate for CKD stage, preventing hyperplasia of the parathyroid glands, avoiding the development of extra-skeletal calcifications, and preventing or reversing the accumulation of toxic substances such as aluminum and β2-microglobulin. In order to limit cardiovascular calcification, daily intake of elemental calcium, including from dietary sources and from phosphate binders, should not exceed twice the daily recommended intake for age and should not exceed 2.5 g/day. Calcium-free phosphate binders, such as sevelamer hydrochloride and sevelamer carbonate, are safe and effective alternatives to calcium-based binders, and their use widens the margin of safety for active vitamin D sterol therapy. Vitamin D deficiency is highly prevalent across the spectrum of CKD, and replacement therapy is recommended in vitamin D-deficient and insufficient individuals. Therapy with active vitamin D sterols is recommended after correction of the vitamin D deficiency state and should be titrated based on target PTH levels across the spectrum of CKD. Although the use of calcimimetic drugs has been proven to effectively control the biochemical features of secondary hyperparathyroidism, there is very limited experience with the use of such agents in pediatric patients and especially during the first years of life. Studies are needed to further define the role of such agents in the treatment of pediatric CKD-MBD.

Figure 1

(a) Changes in bone formation rate (BFR) during treatment with active vitamin D sterols and phosphate binders, (b) plasma parathyroid hormone (PTH) levels throughout the course of the study by treatment group and c) plasma C-terminal fibroblast growth factor 23 (FGF-23) levels throughout the course of the study by treatment group. Treatment groups: 1) 1αD₂ + CaCO₃ (closed diamonds), 2) 1αD₂ + sevelamer (open diamonds), 3) calcitriol + CaCO₃ (closed squares) and 4) calcitriol + sevelamer (open squares). Asterix indicates p<0.01 from baseline.