Clinical Results of Treatment of Diabetes Insipidus with Drugs of the Chlorothiazide Series

Crawford, John D.; Kennedy, G. C.; Hill, Lisa

doi:10.1056/nejm196004142621501

Cited by 84 publications

(40 citation statements)

References 10 publications

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“…The antidiuretic effect of the mercurial reported herein is in contrast to the report of Crawford, Kennedy, and Hill, who observed no antidiuresis during the duration of a "trial period of twentyfour to forty-eight hours" on mersalyl (13). Since mercurial diuretics appear to interfere with the isotonic reabsorption of sodium (30)(31)(32), however, these agents would produce an increased final urine volume, and an antidiuretic effect would only be expected during the period following the mercurial diuresis and prior to a repletion of the losses of sodium.…”

Section: Discussioncontrasting

confidence: 99%

See 1 more Smart Citation

The Mechanism of Antidiuresis Associated With the Administration of Hydrochlorothiazide to Patients With Vasopressin-Resistant Diabetes Insipidus*

Earley¹,

Orloff²

1962

J. Clin. Invest.

193

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Laragh, Heinemann, and Demartini first reported that the administration of chlorothiazide during water diuresis results in an increased rate of solute excretion without significant changes in the rate of urine flow (1,2 repeatedly confirmed (6-13), and the thiazide derivatives have now attained a place of therapeutic usefulness in patients with vasopressinresistant diabetes insipidus (13).Inhibition of solute reabsorption in the distal nephron alone does not account for the antidiuretic effect of the thiazide derivatives. As indicated above, such inhibition of solute reabsorption would merely increase urinary osmolality without affecting urinary volume. Therefore, the mechanism whereby volume is reduced must reside in some other direct or indirect action of these agents. The results of the present studies are consistent with the view that the antidiuretic effect of hydrochlorothiazide is a consequence of the losses of sodium induced by the agent and is not due to any unique property of the thiazide derivatives. The antidiuresis is enhanced by a low sodium intake. is diminished by a high sodium intake, and may also be produced by mercurial diuretics, despite apparent differences in the site and mode of action of the latter agents. METHODSMultiple studies were performed on four hospitalized male subj ects with vasopressin-resistant diabetes insipidus, ranging in age from seven to, seventeen years. Two were brothers, a third had an affected brother, and all had a history of polyuria and polydipsia dating from infancy. Maximal urine osmolalities after a 17-to 20-hour thirst were less than 100 mOsm per kg in three subjects, and not greater than 130 mOsm per kg in one subject (S. Z.). None of the four subjects demonstrated any increase in urinary concentration when dehydration was followed by the administration of vasopressin. All were free of other renal functional abnormalities. The intakes of sodium were controlled by the addition of weighed amounts of sodium chloride to a standard diet containing 9 mEq of sodium. In all instances in which the effects of hydrochlorothiazide were studied, the drug was administered orally, 25 mg every 8 hours. A mini-1988

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Section: Discussioncontrasting

confidence: 99%

“…repeatedly confirmed (6)(7)(8)(9)(10)(11)(12)(13), and the thiazide derivatives have now attained a place of therapeutic usefulness in patients with vasopressinresistant diabetes insipidus (13).…”

mentioning

confidence: 94%

The Mechanism of Antidiuresis Associated With the Administration of Hydrochlorothiazide to Patients With Vasopressin-Resistant Diabetes Insipidus*

Earley¹,

Orloff²

1962

J. Clin. Invest.

193

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“…Chlorpropamide, which facilitates the action of vasopressin on the distal tubule (19,20) and toad bladder (21,22) and is ineffective in nephrogenic diabetes insipidus (23)(24)(25), was likewise ineffective in these patients. The dramatic reduction in polyuria and increase in Uosm after chlorothiazide administration to patients with lithiumI polyuria is consistent with the similar action of this agent in hereditary nephrogenic diabetes insipidus (26,27). While the antidiuresis of chlorothiazide is incompletely understood, it is likely that this agent reduced the deliverv of water to the distal nephron as a conse(luenice of sodium diuresis, (limiiinished GFR, and increased fractional reabsorption of sodium and water in the proximal tubule (28)(29)(30)(31).…”

supporting

confidence: 72%

On the Mechanism of Lithium-Induced Diabetes Insipidus in Man and the Rat

Forrest¹,

Cohen²,

Torretti³

et al. 1974

J. Clin. Invest.

274

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A B S.T R A C T The mechanism of lithium-induced diabetes insipidus was investigated in 96 patients and in a rat model. Polydipsia was reported by 40% and polyuria (more than 3 liter/day) by 12% of patients receiving lithium. Maximum concentrating ability after dehydration and vasopressin was markedly impaired in 10 polyuric patients and was reduced in 7 of 10 nonpolyuric patients studied before and during lithium therapy. Severe polyuria (more than 6 liter/day) was unresponsive to trials of vasopressin and chlorpropamide, but improved on chlorothiazide. Rats receiving lithium (3-4 meq/kg/day) developed massive polyuria that was resistant to vasopressin, in comparison to rats with comparable polyuria induced by drinking glucose. Analysis of renal tissue in rats with lithium polyuria showed progressive increase in the concentration of lithium from cortex to papilla with a 2.9-fold corticopapillary gradient for lithium. The normal corticopapillary gradient for sodium was not reduced by lithium treatment. The polyuria was not interrupted by brief intravenous doses of vasopressin (5-10 mU/kg) or dibutyryl cyclic AMP (10-15 mg/kg) capable of reversing water diuresis in normal and hypothalamic diabetes insipidus rats (Brattleboro strain). The present studies suggest that nephrogenic diabetes insipidus is a common finding after lithium treatment and results

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“…When thiazide diuretics are administered to patients with DI, the effect of reduction in urine volume and elevation of urine osmolality was first observed by Crawford and Kennedy (31) and later confirmed by others (32,33). However, this apparent clinical pharmacologic paradox has not been clearly understood, and the following mechanism has been proposed to account for the antidiuretic effect of thiazides (6,7).…”

Section: Hctz Treatment Partially Reverses Li-induced Aqp2 Downregulamentioning

confidence: 99%

Antidiuretic Effect of Hydrochlorothiazide in Lithium-Induced Nephrogenic Diabetes Insipidus Is Associated with Upregulation of Aquaporin-2, Na-Cl Co-transporter, and Epithelial Sodium Channel

Kim

Lee²,

Oh³

et al. 2004

Journal of the American Society of Nephrology

133

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Abstract. Thiazides have been used in patients with nephrogenic diabetes insipidus (NDI) to decrease urine volume, but the mechanism by which it produces the paradoxic antidiuretic effect remains unclear. Previous studies have reported that downregulation of aquaporin-2 (AQP2) is important for the development of lithium-induced (Li-induced) polyuria and that hydrochlorothiazide (HCTZ) increases renal papillary osmolality and Na ϩ concentration in Brattleboro rats. For elucidating the molecular basis of the antidiuretic action of HCTZ in diabetes insipidus, whether administration of HCTZ may affect the expression of AQP2 and major renal Na ϩ transporters in Li-induced NDI rats was investigated, using semiquantitative immunoblotting and immunohistochemistry. After feeding male Sprague-Dawley rats Li chloride-containing rat diet for 4 wk, HCTZ or vehicle was infused subcutaneously via osmotic minipump. Urine output was significantly decreased by HCTZ treatment, whereas it was not changed in vehicle-treated rats. Urine osmolality was also higher in HCTZ-treated rats than in vehicle-treated rats. Semiquantitative immunoblotting using whole-kidney homogenates revealed that HCTZ treatment caused a significant partial recovery in AQP2 abundance from Li-induced downregulation. AQP2 immunohistochemistry showed compatible findings with the immunoblot results in both cortex and medulla. The abundances of thiazide-sensitive NaCl co-transporter and ␣-epithelial sodium channel were increased by HCTZ treatment. Notably, HCTZ treatment induced a shift in molecular weight of ␥-epithelial sodium channel from 85 to 70 kD, consistent with previously demonstrated aldosterone stimulation. The upregulation of AQP2 and distal renal Na ϩ transporters in response to HCTZ treatment may account for the antidiuretic action of HCTZ in NDI.In nephrogenic diabetes insipidus (NDI), the kidney is unable to concentrate urine despite normal or elevated concentrations of the antidiuretic hormone arginine vasopressin. The acquired form of NDI is much more common than the congenital form, which has mutations either in the vasopressin V 2 receptor gene or in the aquaporin-2 (AQP2) gene (1). Lithium (Li) treatment (2), hypokalemia (3), and ureteral obstruction (4) are three common causes of acquired NDI, and all have been associated with downregulation of AQP2 (2-4).One of the recommended regimens for the treatment of NDI is low-sodium diet coupled with thiazides, although amiloride is preferably used to mitigate Li-induced polyuria in humans because of its blunting the inhibitory effect of Li on water transport in the collecting duct (5). Thiazide diuretics paradoxically decrease urine volume and increase urine osmolality presumably by producing a mild sodium depletion (6). The widely accepted hypothesis suggests that thiazide-induced sodium depletion causes a reduction in distal delivery associated with enhanced fractional water reabsorption in the collecting duct (6,7). However, the mechanism by which thiazide diuretics produce their paradoxic antidi...

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Clinical Results of Treatment of Diabetes Insipidus with Drugs of the Chlorothiazide Series

Cited by 84 publications

References 10 publications

The Mechanism of Antidiuresis Associated With the Administration of Hydrochlorothiazide to Patients With Vasopressin-Resistant Diabetes Insipidus*

The Mechanism of Antidiuresis Associated With the Administration of Hydrochlorothiazide to Patients With Vasopressin-Resistant Diabetes Insipidus*

On the Mechanism of Lithium-Induced Diabetes Insipidus in Man and the Rat

Antidiuretic Effect of Hydrochlorothiazide in Lithium-Induced Nephrogenic Diabetes Insipidus Is Associated with Upregulation of Aquaporin-2, Na-Cl Co-transporter, and Epithelial Sodium Channel

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