Etiology of Hypercalcemia in Hemodialysis Patients on Calcium Carbonate Therapy

Fourteen of 39 dialysis patients (36%) became hypercalcemic after switching to calcium carbonate as their principal phosphate binder. In order to identify risk factors associated with the development of hypercalcemia, indirect parameters of intestinal calcium reabsorption and bone turnover rate in these 14 patients were compared with results in 14 eucalcemic patients matched for age, sex, length of time on dialysis, and etiology of renal disease. In addition to experiencing hypercalcemic episodes with peak calcium values of 2.7 to 3.8 mmol/L (10.7 to 15.0 mg/dL), patients in the hypercalcemic group exhibited a significant increase in the mean calcium concentration obtained during 6 months before the switch, compared with the mean value obtained during the 7 months of observation after the switch (2.4 ± 0.03 to 2.5 ± 0.03 mmol/L [9.7 ± 0.2 to 10.2 ± 0.1 mg/dL], P = 0.006). In contrast, eucalcemic patients exhibited no change in mean calcium values over the same time period (2.3 ± 0.05 to 2.3 ± 0.05 mmol/L [9.2 ± 0.2 to 9.2 ± 0.2 mgldL]). CaCO₃ dosage, calculated dietary calcium intake, and circulating levels of vitamin D metabolites were similar in both groups. Physical activity index and predialysis serum bicarbonate levels also were similar in both groups. However, there was a significant difference in parameters reflecting bone turnover rates between groups. The hypercalcemic patients had significantly lower levels of serum osteocalcin (23 ± 4 v 94 ± 24 ng/mL, P < 0.01), intact parathyroid hormone (PTH; 22 ± 4 v 74 ± 11 pg/nL, P = 0.034), and alkaine phosphatase (89 ± 7 v 120 ± 16 IU/L, P = 0.034) compared with eucalcemic controls. Aluminum burden, as measured by the deferoxamine (DFO) challenge test, was similar in both groups. There was a significant racial difference between the groups, with a predominance of white patients in the hypercalcemic group. The data suggests that low bone turnover rate, and not increased intestinal calcium absorption, is the risk factor most commonly associated with the development of hypercalcemia on CaC03 therapy. Whether this complication occurs more commonly in white patients, as we observed, requires further study for verification.