Changes in calcium excretion after prolonged metolazone therapy in recurrent stone formers

The handling of an acute oral calcium load in 22 men with recurrent calcium stone disease was studied before and after diuretic therapy. As a group, the patients had marginal hypercalciuria (150 mg calcium per gram of creatinine in a 24-hr urine collection). Metolazone, a diuretic with an action in the cortical thick ascending limb of Henle's loop, was given in oral daily doses of 5.0 mg for periods of 9 to 34 mo. An oral calcium load induced a rapid rise in urine calcium exeretion, which was blunted markedly by metolazone. Further analysis of the subjects revealed that one group (11 subjects) had higher baseline 24-hr calcium excretion levels and higher parathyroid hormone (PTH) than the others. The effect of metolazone in reducing the calciuric response was significant only in this group. Thus, while long-term treatment with metolazone inhibited the rise in urinary calcium excretion elicited by an oral calcium load, the effect was significant only in patients who had high baseline urinary calcium and PTH values. The reduction in calcium excretion in response to an acute calcium challenge may explain in part the beneficial effects of cortical diluting segment diuretics in recurrent stone formers.