Exogenous Calcitonin (CT) — A Probe for the State of Mineral Metabolism in Idiopathic Recurrent Calcium Urolithiasis (RCU)

Abstract

Calcitonin (CT), one of the three major calciotropic hormones, binds to renal cortical membranes1, and the kidneys account for about two-thirds of its metabolism2. Interestingly, the possible contribution of endogenous CT to the pathophysiology of RCU, a major health problem worldwide, is unsettled. Subgroups of RCU patients may exhibit postprandial or fasting hypercalciuria, together with high urinary sodium3. Calciuria, magnesiuria, and natriuresis increase in response to exogenous calcitonin4; this would fit with the concept that CT, when present in excess in RCU, at least partially accounts for the hypercalciuria and natriuresis5. On the other hand, reduced calcium eflux from bone and subsequent hypocalcemia are well documented CT effects. These contrast with the reported increased bone resorption in unclassified (according to calciuria) RCU patients6, which makes it unlikely that there is an excess of CT in this disorder. Previously, we failed to demonstrate inappropriate hypercalcitoninemia following an oral calcium challenge in normo- and hypercalciuric RCU7 patients and others have made similar observations when using the same approach8. From all this, we hypothesized that it is not the endogenous CT secretion but rather the CT responsiveness of target organs that could play some critical role in determining urine composition. For instance, exposure of end organs to a defined high CT load may allow more insight into the uptake and degradation of CT, as reflected by the subsequently developed CT blood levels and the associated order of magnitude of response parameter(s). This work reports on nephrogenous cyclic AMP (NcAMP) and the mineral metabolic urinary environment observed after CT administration in RCU patients and volunteers.