Calcium-induced natriuresis: physiologic and clinical implications.
Assessment of the tubular reabsorption of calcium (Ca) by infusion is complicated by suppression of parathyroid hormone (PTH) secretion, and by activation of the serpentine Ca sensing receptor in the renal tubule, which inhibits Ca and sodium reabsorption, but little is known about the magnitude of the natriuretic effect of Ca in human subjects. Accordingly, we reanalyzed the relationship between serum Ca and urine Ca and sodium excretion expressed per unit of creatinine clearance (CaE and NaE), and per unit of time (UCa and UNa), during a standard Ca infusion, in 14 healthy volunteers and in 8 primary hyperparathyroid patients. In healthy subjects we observed a large effect of Ca infusion on NaE, which rose as high as 8 mmol/liter GFR. In patients with primary hyperparathyroidism both CaE and NaE during Ca infusion were significantly lower overall than in healthy subjects for comparable values of serum Ca (P < 0.05 by covariance analysis), due mainly to a decline or reversal of the slopes at the highest serum Ca levels. In both controls and primary hyperparathyroid subjects the variance of CaE as dependent variable was explained by both serum Ca and by NaE as independent variables (P < 0.001). We conclude that (1) The natriuretic effect of hypercalcemia was unexpected large and if maintained would lead to substantial depletion of extracellular fluid. (2) Patients with chronic hypercalcemia, including primary hyperparathyroidism, probably have mild sodium depletion, and are more susceptible to volume depletion. (3) Calcium reabsorption during Ca infusion is reduced by suppression of PTH secretion and increased by volume contraction due to sodium depletion. Discrimination between different basal levels of parathyroid function is successful because these effects usually cancel out. (4) The increase in tubular reabsorption of Ca due to volume contraction can initiate a vicious circle, of importance to the pathogenesis and treatment of severe hypercalcemia.
Adami
S
S
Istituto Semeiotica e Nefrologia Medica, University of Verona, Italy.
Parfitt
A M
AM
D000328:Adult; D002118:Calcium / Q000097:blood / Q000494:pharmacology* / Q000652:urine; D003404:Creatinine / Q000097:blood / Q000652:urine; D005260:Female; D006801:Humans; D006961:Hyperparathyroidism / Q000097:blood / Q000378:metabolism* / Q000652:urine; D007262:Infusions, Intravenous; D008297:Male; D009318:Natriuresis / Q000187:drug effects* / Q000502:physiology; D012964:Sodium / Q000378:metabolism / Q000652:urine; D013997:Time Factors
D012964:Sodium; D003404:Creatinine; D002118:Calcium