DIRECT INHIBITORY EFFECT OF THE SEQUENTIA L INCREMENT IN THE DOSE OF INTRAVENOUS CALCITRIOL ON SECONDARY HYPERPARATHYROIDISM - LONG-TERM EVOLUTION

In 10 hemodialysis patients with severe secondary hyperparathyroidism (PTH > 50 pmol/l and ionized serum calcium, >4.4 mg/dl) we studied the direct inhibitory effect of sequential increments in the dose of intr avenous calcitriol (2.4 and 6 mu g posthemodialysis for 3.2 and 2 mont hs respectively) on parathyroid function. We also analyzed the rate of treatment failures (need for parathyroidectomy) after an 18 month fol low-up. We used a 2.5 mEq/L calcium dialysate and aluminium hydroxide as a phosphate binder to reduce the risk of hyercalcemia. Parathyroid function was measured after the periods of treatment with 2 and 6 mu g intravenous calcitriol by the construction of the sigmoidal Ca-PTH cu rve. Direct, non calcium-mediated inhibition was considered to exist w hen intact PTH levels after maximal stimulation decreased 20 %, or mor e from baseline values. Four patients responded to 2 mu g (table I). I n 3 of the remaining 6 non -responders, the Ca x P product did not all ow us to increase the calcitriol dose. In the other 3 patients reachin g the 6 mu g dose, a response was obtained in only 2 (fig. 2A,2B,2C). After an 18 month follow-up the intravenous calcitriol treatment had f ailed in 50 % of cases, and the remainder were kept on treatment with lower maintenance doses than the initial ones. To summarize, high dose intravenous calcitriol: 1) Exerts a dose dependent inhibitory effect on PTH levels. 2) In the long term permits maintenance doses lower tha n those that induced the response, suggesting a ''sensitizing'' effect over the parathyroid cells, and 3) Despite this, has a high failure r ate (50%).