The objective of this study was to evaluate the hypothesis that a high concentration of ionized calcium in the lumen of the medullary collecting duct causes an osmole-free water diuresis. The urine flow rate and osmolality were measured in normal human subjects, as well as in patients with a history of nephrolithiasis who excreted more than 5 mmol of calcium per 24 h. There was an inverse relationship between the concentration of calcium in the urine and the 24 h urine volume both in normal subjects and in patients with a history of nephrolithiasis. When the concentration of calcium in the urine was greater than 5 mmol/l, the urine volume was less than 1 litre per day in the majority of subjects. After 16 h of water deprivation, when the concentration of calcium in the urine was as high as 17 mmol/l (ionized calcium 7.4 mmol/l), urine osmolality was 1258 mOsm/kg of water and the urine flow rate was 0.30 ml/min. We conclude that, although a calcium receptor may be present in the lumen of the medullary collecting duct in human subjects, an extremely high concentration of urinary total and ionized calcium does not cause a clinically important defect in the renal concentrating process.

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