Reduction of Dialysate Calcium Level Reduces Progression of Coronary Artery Calcification and Improves Low Bone Turnover in Patients on Hemodialysis

Abstract

Exposure to high Ca concentrations may influence the development of low-turnover bone disease and coronary artery calcification (CAC) in patients on hemodialysis (HD). In this randomized, controlled study, we investigated the effects of lowering dialysate Ca level on progression of CAC and histologic bone abnormalities in patients on HD. Patients on HD with intact parathyroid hormone levels ≤300 pg/ml receiving dialysate containing 1.75 or 1.50 mmol/L Ca (n=425) were randomized to the 1.25-mmol/L Ca (1.25 Ca; n=212) or the 1.75-mmol/L Ca (1.75 Ca; n=213) dialysate arm. Primary outcome was a change in CAC score measured by multislice computerized tomography; main secondary outcome was a change in bone histomorphometric parameters determined by analysis of bone biopsy specimens. CAC scores increased from 452±869 (mean±SD) in the 1.25 Ca group and 500±909 in the 1.75 Ca group (P=0.68) at baseline to 616±1086 and 803±1412, respectively, at 24 months (P=0.25). Progression rate was significantly lower in the 1.25 Ca group than in the 1.75 Ca group (P=0.03). The prevalence of histologically diagnosed low bone turnover decreased from 85.0% to 41.8% in the 1.25 Ca group (P=0.001) and did not change in the 1.75 Ca group. At 24 months, bone formation rate, trabecular thickness, and bone volume were higher in the 1.25 Ca group than in the 1.75 Ca group. Thus, lowering dialysate Ca levels slowed the progression of CAC and improved bone turnover in patients on HD with baseline intact parathyroid hormone levels ≤300 pg/ml.

Keywords: hemodialysis; mineral metabolism; vascular calcification.

Figure 1.

Disposition of patients. Among 894 patients treated in eight dialysis clinics, 425 subjects were randomized to either 1.25 or 1.75 mmol/L dialysate Ca groups. After 24 months of follow-up period, 284 patients completed the study (150 in the 1.25 and 134 in the 1.75 Ca groups). AE, adverse event; CT, computerized tomography; spKt/V, single pool Kt/V.

Figure 2.

Higher CAC progression in the 1.75 Ca group than 1.25 Ca group (160±299 versus 303±624, P=0.03) (A); in the whole group, higher CAC progression in patients with serum phosphorus level ≥4.7 compared to <4.7 mg/dl (292±576 versus 160±342, P=0.03) (B); in patients with serum phosphorus level ≥4.7 mg/dl, higher CAC progression with 1.75 than 1.25 mmol/L dialysate Ca (485±801 versus 171±324, P=0.01 (C); in patients with serum phosphorus level <4.7 mg/dl, similar CAC progression in the 1.75 and 1.25 Ca groups (157±274 versus 158±386, P=0.98) (C).