Thiazide-lnduced Rise in Serum Calcium and Magnesium in Patients on Maintenance Hemodialysis

219

A B S T R A C T Studies were undertaken in man to evaluate the roles of volume depletion and of the parathyroid glands in mediating the changes in serum and urinary calcium which follow the administration of hydrochlorothiazide, 100 mg twice daily, for 4 days. 42 studies were carried out in 16 normal subjects, 9 patients with hyperparathyroidism, and 7 vitamin D-treated subjects with hypoparathyroidism. In six studies in normal subjects, daily sodium losses during thiazide administration were quantitatively replaced, and in six other studies the effect of equivalent sodium losses produced by furosemide was evaluated.Although the magnitude of sodium losses was similar in three groups during therapy with thiazides, urinary calcium fell and urinary phosphorus increased significantly only in normal subjects and those with hyperparathyroidism; no change occurred in patients with hypoparathyroidism. With the replacement of the thiazide-induced sodium losses by NaCl in normals, urinary calcium did not change as urinary sodium increased 4-to 5-fold. Furosemide administration produced similar sodium losses while urinary calcium remained at or above control levels. After correction for changes in plasma protein concentration caused by thiazide-induced hemoconcentration, mean levels of serum calcium were significantly increased only in subjects with hyperparathyroidism and vitamin D-treated patients with hypoparathyroidism.

mentioning

confidence: 56%

Changes in Serum and Urinary Calcium during Treatment with Hydrochlorothiazide: Studies on Mechanisms

Brickman¹,

Massry²,

Coburn³

1972

219

“…The plasma calcium remains normal even after many years in the great majority of patients given a thiazide (4,6,10,11), but in a few it may rise significantly (10,11). This is especially likely in patients with primary hyperparathyroidism (10) and in anephric patients with secondary hyperparathyroidism on maintenance hemodialysis (12). These observations suggested that thiazides might enhance the peripheral actions of parathyroid hormone (PTH)1 on kidney and bone (10,12).…”

Section: Introductionmentioning

confidence: 95%

“…This is especially likely in patients with primary hyperparathyroidism (10) and in anephric patients with secondary hyperparathyroidism on maintenance hemodialysis (12). These observations suggested that thiazides might enhance the peripheral actions of parathyroid hormone (PTH)1 on kidney and bone (10,12).…”

Section: Introductionmentioning

confidence: 99%

The interactions of thiazide diuretics with parathyroid hormone and vitamin D

Parfitt¹

1972

114

A B S T R A C T In order to clarify the mechanisms of thiazide diuretic-induced hypocalciuria, the effect of a thiazide was studied for 7 days in seven patients with hypoparathyroidism on Vitamin D and one on calcium infusion, and seven euparathyroid patients with hypercalciuria. In the control group, calcium excretion (mg/24 hr) fell by 44% from 415 to 232 within 4 days and remained at this level. Plasma total calcium corrected for total protein did not change. In the hypoparathyroid group, calcium excretion fell by 11% from 351 to 311 and then returned to the base line level. Plasma total calcium (mg/100 ml) increased from 10.09 to 10.88, 11.29 and 10.77 at the end of the 2nd, 4th, and 7th day of thiazide administration. In the patient having i.v. calcium and no Vitamin D, neither plasma nor urinary calcium changed significantly. In both groups sodium excretion increased on the first 2 days and fell to or below base line level thereafter. Urinary phosphate, magnesium, and potassium increased, plasma phosphate rose, and magnesium and potassium fell. It is concluded that: (a) The hypocalciuric effect of thiazides requires the presence of parathyroid hormone and is not solely a result of sodium depletion. (b) The hypercalcemic effect of thiazides in hypoparathyroidism is due to increased release of calcium from bone and requires the presence of a pharmacologic dose of Vitamin D. (c) Thiazides enhane the action of parathyroid hormone on bone and kidney; Vitamin D can replace parathyroid hormone in this interaction in bone but not in kidney.

“…Such a dependence could either involve stimulation of PTH secretion (15) or potentiation of its peripheral action by CTZ (3). Both possibilities were considered in previous studies (3)(4)(5). The hypercalcemic action of PTH is a result of its skeletal mobilization of calcium and increased gastrointestinal absorption of calcium (16)(17)(18)(19).…”

Section: Resultsmentioning

confidence: 99%

“…The mechanism of thiazide-induced hypercalcemia has been the subject of numerous investigations (1)(2)(3)(4)(5)(6)(7)(8). Although hypercalcemia has been noticed primarily in patients with high rates of bone turnover (2,3,5), significant increases in serum calcium concentration were also reported in normal individuals treated with thiazide diuretics (1,7).…”

Section: Introductionmentioning

confidence: 99%

The acute effect of chlorothiazide on serum-ionized calcium. Evidence for a parathyroid hormone-dependent mechanism.

Popovtzer¹,

Subryan²,

Alfrey³

et al. 1975

A B S T R A C T The acute effects of chlorothiazide (CTZ) on total (TSCA) and ionized (SCA2') serum calcium concentrations were studied in three groups of people: (a) eight subjects with normal parathyroid function; (b) six patients with hypoparathyroidism; and (c) two patients with hyperparathyroidism. Most subjects were studied on four occasions; at least 3 days intervened between studies on an individual subject. During each experiment the subject received an i.v. infusion of 5% dextrose in water at 1 ml/min from 8 a.m. to 4 p.m. Additions to the infusions were (a) none; (b) CTZ to deliver 3.33 mg/kg/h; (c) parathyroid extract to deliver 1 U/kg/h; or (d) both CTZ and parathyroid extract at the rates previously indicated. CTZ, when used, was added to the infusion at 10 a.m., parathyroid extract at 8 a.m. When CTZ was infused, the diureticinduced losses of Na and water were replaced by i.v. infusion. In normal subjects 2 h after the start of CTZ infusion, there was a transient increase in SCA +2 which coincided in time of day with a transient decrease in SCA+2 in control experiments. At that time of day SCA+2 was 4.18±0.12 mg/100 ml in control experiments and 4.56±0.08 in experiments with CTZ, P < 0.025. The corresponding values for (TSCA) were 9.32±0.15 and 9.80+0.30, P < 0.01. Such differences were not observed in the group with hypoparathyroidism. In the two patients with hyperparathyroidism, CTZ produced sustained increases in TSCA and SCA+'. In normal subjects and those with hypoparathyroidism, CTZ plus parathyroid extract infusion resulted in sustained increases in both