It is well known that patients with hypercalcemia of diverse etiologies may exhibit marked polyuria (1-5). The increased rate of urine formation is often associated with considerable losses of urinary solute and sometimes results in severe depletion of extracellular salt and water stores (6). This urinary wastage has been attributed to slowly developing pathological changes in the renal tubules produced by prolonged hypercalciuria and nephrocalcinosis. It is possible, however, that the renal response may in part be conditioned by a direct and immediate physiological effect of the hypercalcemia and/or hypercalciuria. The studies of Wolf and Ball in which calcium infusions in the dog provoked a prompt increase in the rate of sodium excretion (7) May, 1956. and contained proper quantities of inulin and PAH for the measurement of renal clearances. Comparable solutions free of calcium were administered at the same rate before and after the calcium infusion. Three to four 20 minute control periods were obtained prior to the calcium infusion, during which inulin and PAH clearances and the control rates of sodium, chloride, potassium, calcium, phosphorus and ammonium (pH and bicarbonate in some experiments) excretion were determined. Similar measurements were made in four 20 minute periods during the calcium infusion, and for two to three comparable periods after the calcium infusion was discontinued. Standard catheter and air flush techniques were used for bladder emptying and clearance determinations. During the control period at least two and generally three heparinized blood samples were obtained for the determination of plasma calcium, phosphorus, sodium, potassium, chloride, bicarbonate, inulin and PAH concentrations. Similar measurements were repeated at 15 minute intervals during the calcium infusion and after its discontinuation. The calcium infusion studies were performed in five resting normal adults in a fasting state and in three normal fasting cynomolgus monkeys. Similar measurements were made in man before and after a single intravenous injection of 10 ml., 20 ml., and 40 ml. of 10 per cent calcium gluconate solution, respectively. These single injection experiments were performed in seven normal fasting male subjects.After the typical response to a standard rapid injection of 20 ml. of calcium gluconate was evaluated, similar loads were administered to eight patients in whom the urine had been either alkalinized or acidified with appropriate prior therapy. In the latter subjects sodium bicarbonate or ammonium chloride solutions of 150 mEq. per liter were administered at the rate of 2 ml. per minute for 90 minutes before and for a similar period after the injection of the calcium load. In these subjects, measurements similar to those mentioned above were made during the acidifying or alkalinizing infusion both before and after the administration of the calcium load.The plasma calcium concentration was reduced in three normal patients by the infusion of a chelating solution. Sodium Versenate®D (sodium...

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