On the Hypocalciuric Action of Chlorothiazide

Costanzo, Linda S.; Weiner, I. M.

doi:10.1172/jci107800

Cited by 107 publications

(37 citation statements)

References 31 publications

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“…The hypocalciuric effect of HCTZ is gen erally attributed to enhanced renal tubular reabsorption of calcium and to volume con traction and a fall in GFR [3][4][5][6][7], In our study GFR was not altered by HCTZ but, as in previous studies [3][4][5][6][7], this drug did elevate total plasma calcium. Although ultrafilterable calcium levels were not measured in our study, others report that a rise [3] or no change [7] in ultrafilterable calcium is asso ciated with thiazide-mediated elevation of total plasma calcium.…”

Section: Discussionsupporting

confidence: 80%

“…Thiazide diuretics are widely used to treat hypercalciuria in patients with kidney stones [1,2], They have a potent but poorly understood hypocalciuric action [3][4][5][6][7][8][9][10], So dium bicarbonate also lowers urinary cal cium excretion [11][12][13][14][15][16], Our study was un dertaken to determine whether varying the delivery ofbicarbonate to the distal region of the nephron would alter the ability of thia zide diuretics to lower urinary calcium in the rat. It seemed possible that the hypocalciuric effects of thiazides might be mediated, at least in part, via changes in bicarbonate in tubular fluid.…”

Section: Introductionmentioning

confidence: 99%

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Hypocalciuric Effects of Hydrochlorothiazide in the Rat during NaHCO3, NaCl and NH4C1 Loading

Goulding¹,

Campbell²

1984

Kidney Blood Press Res

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Hydrochlorothiazide (HCTZ) and NaHCO₃ each lower urinary calcium excretion, while NaCl and NH₄Cl each increase urinary calcium. This study examines the ability of HCTZ to lower urinary calcium during NaHCO₃, NaCl and NH₄Cl loading in the rat. We show that HCTZ lowers urinary calcium in rats treated with NaHCO₃, NaCl and NH₄Cl. We demonstrate that urinary calcium excretion is depressed to a greater degree by administering NaHCO₃ and HCTZ in combination than by administering these agents separately.

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Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Hypocalciuric Effects of Hydrochlorothiazide in the Rat during NaHCO3, NaCl and NH4C1 Loading

Goulding¹,

Campbell²

1984

Kidney Blood Press Res

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“…As has been domonstrated previously, there are two mechanisms by which the thiazides reduce calcium excretion: (1) by the decrease in extracellular fluid volume and hence by nonspecific stimulation of the sodium-coupled calcium reabsorption in the proximal tubule (2,3,21) and (2) by specific dissociative action on the distal tubule, which results in enhanced reabsorption of calcium in contrast to decreased reabsorption of sodium (6,8,9). This dissociation of calcium/sodium reabsorptions is also evident in the present study (Table 2), as the ratio of urine calcium excretion to urine sodium excretion decreased with chlorothiazide administration.…”

Section: Methodsmentioning

confidence: 89%

Reversal of Vitamin-D2-Induced Hypercalciuria by Chlorothiazide

1983

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Summarydaily subcutaneous injection of 0.2 ml of the vitamin-DzTo test the effects of chlorothiazide on vitamin-D2-induced hypercalciuria, we carried out 17 metabolic studies lasting 12 days each in adult Sprague-Dawley male rats. Three groups were studied: (A) control rats receiving only the vitamin-D2 vehicle; (B) vitamin-D2-treated rats receiving 50 IU/day; and (C) rats treated in the same manner as group B with the addition of chlorothiazide 20 mg/day for the last 6 days of the study. Urine was collected during the last 3 days, and a blood sample was obtained at the end of each study period. Analysis of the data showed that there were no significant differences between the groups in changes of serum calcium concentration (A, 6.1 + 0.1 mg/dl; B, 6.1 f 0.2 mg/dl; C, 6.0 f 0.2 mg/dl), serum creatinine concentration (A, 0.5 + 0.07 mg/dl; B, 0.52 f 0.08 mg/dl; C, 0.48 k 0.04 mg/dl), and creatinine clearance (A, 4.8 f 0.7 ml/min/kg; B, 5.2 + 1.2 ml/min/kg; C, 4.9 f 0.5 ml/min/kg). The administration of vitamin-D2 significantly increased the urinary calcium excretion from 6.7 f 1.0 mg/kg/ day to 19.5 f 9.7 mg/kg/day ( p < 0.02), but the calciuria was inhibited in group C rats by the addition of chlorothiazide, which restored urinary calcium excretion to 6.8 + 2.5 mg/kg/day ( p < confirmed these effects of vitamin-D2 and chlorothiazide on urine calcium excretion. We conclude that in rats conventional doses of vitamin-D2 consistently induce marked hypercalciuria, even witbout hypercalcemia, and that this hypercalciuria can be effectively prevented by chlorothiazide. vehicle only; Group B, the vitamin-Dz group was composed of six rats that were injected daily subcutaneously with 50 IU of vitamin-DP (Drisdol, Winthrop Laboratories, New York, NY); and Group C, the vitamin-Dz and chlorothiazide group included six rats that were treated in the same manner as those in Group B but additionally with chlorothiazide 20 mg/day injected intraperitoneally (Diuril, Merck Sharp and Dohme, West Point, PA) for the last six days. During the last 3 days of the study all urine was collected, mixed, and measured. At the end of the study a blood sample was obtained from each rat by aortic puncture.0The urine was analyzed for calcium, creatinine, and sodium, and the serum for calcium and creatinine. Calcium was determined by atomic absorption spectrophotometry, nonchromogen creatinine, and sodium by standard methods. Student's t test was used to determine the significance of the difference between the groups.

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“…Some investigators [23] propose the fall in urinary calcium as a result of extracellular fluid volume depletion, second ary to the sodium losses produced by the diuretics, others [15,17] suggest that PTH is required for this action, and that the drug may directly stimulate the parathyroid glands or produce an enhancement of the renal calcium-retaining action by PTH. Fi nally, experiments carried out in animals [24,25] suggest that thiazide diuretics may directly increase calcium reabsorption by the distal tubule. The hypocalciuric effect of in dapamide seems to be unrelated to extracel lular volume depletion because the natri uretic action of the drug was very low and the fall in calcium excretion was already evi dent on the 1st day of treatment.…”

Section: Time Daysmentioning

confidence: 99%

Acute Effect of Indapamide on Urine Calcium Excretion in Nephrolithiasis and Human Essential Hypertension

Borghi¹,

Elia²,

Trapassi³

et al. 1988

Pharmacology

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The effects of indapamide (2.5 mg once a day) on urinary composition are reported in 20 patients (10 with recurrent calcium nephrolithiasis and 10 with essential hypertension) compared with 20 controls. Indapamide was well absorbed in every patient (mean plasma level at the steady state was 111 ± 41 ng/ml) and its antihypertensive action was more pronounced in hypertensive than in normotensive patients. It lowered calcium excretion in 18/20 patients (mean fall on the 7th day of treatment: 53%) and raised the Mg/Ca ratio in 20/20 patients (mean increase on the 7th day: 167%). The effect on Ca²⁺ and Mg²⁺ excretion was not associated with a strong diuretic effect. During intravenous calcium loading (0.375 mmol/kg body weight) 6 normal subjects after a single oral dose of indapamide excreted less calcium, suggesting a direct renal hypocalciuric action by the drug. Indapamide could represent an alternative drug to thiazide diuretics in diseases with dangerous renal calcium losses, but long-term studies are needed.

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On the Hypocalciuric Action of Chlorothiazide

Cited by 107 publications

References 31 publications

Hypocalciuric Effects of Hydrochlorothiazide in the Rat during NaHCO<sub>3</sub>, NaCl and NH<sub>4</sub>C1 Loading

Hypocalciuric Effects of Hydrochlorothiazide in the Rat during NaHCO<sub>3</sub>, NaCl and NH<sub>4</sub>C1 Loading

Reversal of Vitamin-D2-Induced Hypercalciuria by Chlorothiazide

Acute Effect of Indapamide on Urine Calcium Excretion in Nephrolithiasis and Human Essential Hypertension

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