Effect of Thiazides on the Urinary Calcium Oxalate Stone-Forming Potential in Normal Males

Abstract

We studied the effect of bendroflumethiazide on a risk factor index, COSP, reflecting the stone-forming potential of urinary calcium oxalate. This index includes the concentrations of three stone promotors: calcium, oxalate, and uric acid in its numerator, and two stone inhibitors: magnesium and citrate, in its denominator. These risk factors were measured in 4-hour and 24-hour urinary specimens obtained under fixed conditions of food and fluid intake. Eight normal males were studied before and after two and four weeks of continued thiazide treatment. Thiazide 2.5 mg b.i.d. was given for two weeks, followed by 2.5 mg t.i.d. for another two weeks. Before treatment COSP exhibited a pronounced diurnal variation with peaks between 8 a.m. and noon, and 8 p.m. and midnight. After four weeks of thiazide treatment suppression of two stone promotors, calcium (p less than 0.01) and uric acid (p less than 0.02), and reduced COSP by 36 to 95% in each subject (median: -71%, p less than 0.01). Moreover, thiazide abolished the diurnal variation of COSP. After the initial two weeks of thiazide 2.5 mg b.i.d., almost identical effects were observed. Nearly all the changes in COSP were explained by the effects on urinary calcium. This marked suppression of COSP supports the theory that thiazides may be useful in the prevention of renal calcium oxalate stone formation.

Calcium salt crystalluria in a captive chimpanzee (Pan troglodytes) population

“…Out of several individuals on hydrochlorothiazide during the study period, only one provided a sample with crystalluria present, in the form of calcium oxalate dihydrate crystals. The chimpanzees on hydrochlorothiazide in the study population were prescribed the medication for treatment of heart disease; however, hydrochlorothiazide can also be used to treat calcium oxalate lithiasis 42,43 . Thiazides decrease urinary calcium, preventing calcium salt crystal formation due to hypercalciuria 42,43 .…”

“…The chimpanzees on hydrochlorothiazide in the study population were prescribed the medication for treatment of heart disease; however, hydrochlorothiazide can also be used to treat calcium oxalate lithiasis 42,43 . Thiazides decrease urinary calcium, preventing calcium salt crystal formation due to hypercalciuria 42,43 . However, hyperoxaluria is considered a more significant risk factor for calcium oxalate crystal formation than hypercalciuria 44 ; in one study, calcium oxalate monohydrate frequency was greater in patients treated with thiazides than in those who were not despite the decreased calciuria 42 .…”

“…42,43 Thiazides decrease urinary calcium, preventing calcium salt crystal formation due to hypercalciuria. 42,43 However, hyperoxaluria is considered a more significant risk factor for calcium oxalate crystal formation than hypercalciuria 44 ; in one study, calcium oxalate monohydrate frequency was greater in patients treated with thiazides than in those who were not despite the decreased calciuria. 42 The administration of hydrochlorothiazide should be considered as a possible explanation for crystalluria in chimpanzees.…”