The Pathogenesis of Idiopathic Hypercalciuria: Evidence for Renal Tubular Calcium Leak

Abstract

A standard oral calcium loading test has been employed in a group of idiopathic hypercalciuria (IH) subjects and in a group of marginally hypercalcaemic subjects with primary hyperparathyroidism (PHPT) in whom the diagnosis was revealed by careful combined measurements of serum ionized calcium and immuno-reactive parathyroid hormone (iPTH). Initial values for serum ionized calcium and creatinine clearance were similar in IH and in a control group of normal subjects, whereas iPTH levels were normal or low. Following oral loading, serum ionized calcium rose to similar levels in both IH and control subjects, with no suggestion of relative hypercalcaemia due to a postulated intestinal hyperabsorption in the IH group. A renal tubular calcium 'leak' was however clearly evident in the IH group, in both the fasting and post-absorptive phase. In the marginally hypercalcaemic PHPT subjects on the other hand, a relative post-absorptive hypercalcaemia was clearly apparent, as well as a gross renal tubular calcium leakage. Thus careful preliminary separation of masked PHPT from IH subjects is an essential step before evaluation of response to oral calcium challenge in stone-forming subjects. When this is done, no evidence of a relative post-absorptive hypercalcaemia can be seen in the residual IH group, and hypercalciuria appears to be 'renal' rather than 'absorptive' in origin.