Effect of Chlorthalidone and Hydrochlorothiazide on 12-Hour vs 24-Hour Urinary Calcium Excretion

Urine calcium excretion (UCa) is greater after dinner and urine volumes are lower. The result is higher urine calcium concentrations, which may confer greater risk of stone formation, at night. We considered whether nighttime administration-as compared with daytime administration-of thiazides would be more effective for stone prevention.

We performed 12-hour urine collections in 7 patients taking 25 mg of chlorthalidone (CTD) and 10 patients taking 25 mg of hydrochlorothiazide (HCTZ). Participants completed urine collections at baseline, again after a week of morning medication administration, and again after a week of evening administration, all on repeated self-selected diets.

CTD reduced UCa for both 12-hour periods whether administered in the morning or in the evening: Morning dosing lowered urine calcium from 130 ± 70 mg/g creatinine (Cr) at baseline to 76 ± 52 mg/g Cr (P < .02); evening dosing lowered it to 87 ± 51 mg/g Cr, which was not significant. On the other hand, HCTZ did not reduce UCa regardless of the time of administration: Mean 24-hour UCa was 124 ± 38 mg/g Cr at baseline and 106 ± 40 mg/g Cr when HCTZ was given in the morning and 117 ± 54 mg/g Cr when given in the evening.

We conclude that the long-acting and more effective CTD is a preferable agent for stone prevention. Time of administration does not seem to be important, although morning administration may more effectively address higher postdinner calcium excretion. The most commonly used thiazide (HCTZ) is shorter acting, frequently dosed once per day, but does not seem to reduce UCa at this dose.