HYPERPARATHYROIDISM, GLUCOSE-TOLERANCE AND PLATELET INTRACELLULAR FREE CALCIUM IN CHRONIC-RENAL-FAILURE

Disturbance in the vitamin D/parathyroid hormone (PTH) axis may be imp ortant in the pathogenesis of glucose intolerance and insulin resistan ce in uraemia. To investigate possible relationships between hyperpara thyroidism, intracellular free calcium ([Ca2+](i), and glucose toleran ce in chronic renal failure, we measured serum intact PTH (I-PTH) by t wo-site immunometric assay, platelet [Ca2+](i) using the fluorescent i ndicator fura-2, and plasma glucose and insulin after 14 h overnight f ast and at 30, 60 and 120 min following a 75 g oral glucose load, in 1 8 chronic haemodialysis patients with elevated serum I-PTH. Calcitriol (1 mu g) was administered parenterally at the end of each dialysis se ssion for four weeks. This significantly decreased serum I-PTH (p < 0. 001) and platelet [Ca2+](i) (p < 0.01). Uraemic patients initially sho wed marked glucose intolerance, with increased area below the glucose curve compared to healthy controls, but after 4 weeks of calcitriol tr eatment, this effect was significantly decreased, and there was a sign ificant rise in the area under the insulin curve after glucose load. T he insulinogenic index also increased significantly after calcitriol t reatment. These data suggest that calcitriol treatment of haemodialysi s patient with secondary hyperparathyroidism is associated with increa sed insulin secretion in response to glucose challenge, and that this change is linked to the decrease in intracellular free calcium.