Effect of calcium-channel blockers on calcium-phosphate metabolism in patients with end-stage renal disease

Abstract

Background. After EDTA-induced hypocalcaemia, healthy volunteers treated with diltiazem display more severe hyperparathyroidism than subjects on felodipine studied under identical conditions. Therefore patients with end-stage renal disease (ESRD) and severe secondary hyperparathyroidism might be particularly sensitive to this side-effect. Methods. To test this hypothesis, seven patients with ESRD on chronic haemodialysis (3 women and 4 men) with serum levels of intact PTH ranging from 204 to 675 pg/ml were studied both before and during the first 180 min of haemodialysis against a dialysate with low calcium concentration (0.75 mmol/l, n=6 and 1 mmol/l, n=1) under the following three experimental conditions: control, felodipine (10 mg/day) and diltiazem (120 mg b.i.d.). Results. At onset of dialysis, plasma phosphorus level was higher on diltiazem (2.03 ± 0.08 mM) than on felodipine (1.64 ± 0.10, P<0.02), and on the latter it was lower than in control condition (1.88 ± 0.16, P<0.02). As a probable consequence, blood ionized calcium concentration was lower on diltiazem (1.14mM ± 0.02, mean ± SEM.) than on felodipine (1.2 ± 0.03, P<0.05) or in control condition (1.17 ± 0.01, NS). There was a trend for intact PTH to be higher on diltiazem (324 ± 47 pg/ml) than on felodipine (246 ± 55) or in control condition (305 ± 49) and 1,25-dihydroxyvitamin D was higher indeed on diltiazem (6.70 ± 0.92 pg/ml) than on felodipine (4.75 ± 0.91, P<0.02) or control (3.87 ± 0.62, P< 0.05). Area under the curve PTH over the first 60 min of dialysis was higher by 16 ± 7% on diltiazem than on felodipine (P<0.05). Conclusions. While on diltiazem rather than on felodipine, patients with ESRD display higher plasma phosphorus levels, and slightly aggravate the degree of severity of hyperparathyroidism recorded during haemodialysis against low-calcium dialysate. The long-term effect of this new observation remains to be evaluated.