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

Abstract

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. 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.). 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 (1.14 mM +/- 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). 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.