The interactions of thiazide diuretics with parathyroid hormone and vitamin D

Parfitt, A. M.

doi:10.1172/jci106990

Cited by 114 publications

(50 citation statements)

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“…The mechanism of chronic TZ hypocalciuria is unclear. In short-term studies, administration of TZ causes modest Na depletion, which is associated with a fall in urine Ca excretion; the hypocalciuria can be prevented by administration of sodium chloride (6,7,30,32). However, these studies have rarely included subjects with IH and usually were limited to a week or less in duration.…”

mentioning

confidence: 99%

Role of proximal tubule in the hypocalciuric response to thiazide of patients with idiopathic hypercalciuria

Bergsland

Worcester

Coe

2013

American Journal of Physiology-Renal Physiology

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Bergsland KJ, Worcester EM, Coe FL. Role of proximal tubule in the hypocalciuric response to thiazide of patients with idiopathic hypercalciuria. Am J Physiol Renal Physiol 305: F592-F599, 2013. First published May 29, 2013 doi:10.1152/ajprenal.00116.2013The most common metabolic abnormality found in calcium (Ca) kidney stone formers is idiopathic hypercalciuria (IH). Using endogenous lithium (Li) clearance, we previously showed that in IH, there is decreased proximal tubule sodium absorption, and increased delivery of Ca into the distal nephron. Distal Ca reabsorption may facilitate the formation of Randall's plaque (RP) by washdown of excess Ca through the vasa recta toward the papillary tip. Elevated Ca excretion leads to increased urinary supersaturation (SS) with respect to calcium oxalate (CaOx) and calcium phosphate (CaP), providing the driving force for stone growth on RP. Thiazide (TZ) diuretics reduce Ca excretion and prevent stone recurrence, but the mechanism in humans is unknown. We studied the effect of chronic TZ administration on renal mineral handling in four male IH patients using a fixed three meal day in the General Clinical Research Center. Each subject was studied twice: once before treatment and once after 4 -7 mo of daily chlorthalidone treatment. As expected, urine Ca fell with TZ, along with fraction of filtered Ca excreted. Fraction of filtered Li excreted also fell sharply with TZ, as did distal delivery of Ca. Unexpectedly, TZ lowered urine pH. Together with reduced urine Ca, this led to a marked fall in CaP SS, but not CaOx SS. Since CaOx stone formation begins with an initial CaP overlay on RP, by lowering urine pH and decreasing distal nephron Ca delivery, TZ might diminish stone risk both by reducing CaP SS, as well as slowing progression of RP. calcium oxalate; calcium phosphate; idiopathic hypercalciuria; kidney calculi; thiazide THE MOST COMMON METABOLIC abnormality found in calcium (Ca) stone formers is so-called idiopathic hypercalciuria (IH) (40). Patients with IH absorb more Ca from a given meal than normal people (N), but also have abnormally decreased renal tubule Ca reabsorption, so that they often excrete more Ca than they have absorbed, exhibit decreased bone density, and have a propensity for increased fractures (22,42). Elevated urine Ca excretion leads to increased urinary supersaturation (SS) with respect to both calcium oxalate (CaOx) and calcium phosphate (CaP), providing the driving force for kidney stone formation (36). In addition, urine Ca excretion is correlated with the amount of interstitial apatite deposits (called Randall's plaque) found on the surface of the renal papillae (19). These deposits are the attachment sites for most CaOx stones and appear to be critical for stone formation (14). A plausible mechanism by which increased Ca reaches the deep papillae is via washdown from reabsorption in the thick ascending limb; an increase in delivery of Ca to this site would tend to increase reabsorption and washdown into the papilla and potentially increase...

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confidence: 99%

Role of proximal tubule in the hypocalciuric response to thiazide of patients with idiopathic hypercalciuria

Bergsland

Worcester

Coe

2013

American Journal of Physiology-Renal Physiology

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“…Up to 1 week of treatment Earlier studies in renal stone 'formers', normal and hypertensive subjects showed an initial increase in Mgu (25-70%) following thiazide diuretics, generally falling to, or near, control values within 3 or 4 days [87][88][89]. However these studies were poorly controlled, being of a before and after type (B/A).…”

Section: Animalsmentioning

confidence: 98%

Untitled

1993

Brit J Clinical Pharma

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2 Methods for the measurement of intracellular free magnesium levels are now available and are more relevant to the assessment of magnesium deficiency than total intracellular magnesium content; the complex relationship between intracellular free and total magnesium content remains to be defined. Future work involving the effect of diuretics on intracellular free magnesium measurements should make every attempt to avoid the errors of trial design and multiple publication that litter current and past literature.

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“…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%

“…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%

“…In addition thiazides may act directly on the kidney to enhance tubular reabsorption of calcium ( 11). Mobilization of mineral from the bone has been proposed as another mechanism for the thiazide-induced increase in serum calcium (3,5). This mechanism was considered to be most effective in states of rapid bone turnover, such as hyperparathyroidism, or during an intake of large dose of vitamin D (2,3,5).…”

Section: Introductionmentioning

confidence: 99%

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

Popovtzer¹,

Subryan²,

Alfrey³

et al. 1975

J. Clin. Invest.

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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

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The interactions of thiazide diuretics with parathyroid hormone and vitamin D

Cited by 114 publications

References 32 publications

Role of proximal tubule in the hypocalciuric response to thiazide of patients with idiopathic hypercalciuria

Role of proximal tubule in the hypocalciuric response to thiazide of patients with idiopathic hypercalciuria

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

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