Lithium-induced nephrogenic diabetes insipidus: in vivo and in vitro studies

Singer, Irwin; Rotenberg, Donald; Puschett, Jules B.

doi:10.1172/jci106900

Cited by 178 publications

(47 citation statements)

References 18 publications

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“…The latter is well recognised in the literature (Thomsen, 1970;Singer et al, 1972;Forrest et al, 1974).…”

Section: Discussionmentioning

confidence: 84%

“…Lithium can produce a reversible nephrogenic diabetes insipidus in rats and man (Thomsen, 1970;Singer, Rotenberg & Puschett, 1972;Forrest, Cohen, Torretti, Himmelhoch & Epstein, 1974; Harris & Jenner, 1972). This is probably due in part to the inhibition of the renal vasopressin-sensitive adenyl cyclase (Dousa & Hechter, 1970), but there also seems to be evidence for the inhibition of the antidiuretic action of cyclic AMP (Harris & Jenner, 1972;Forrest et aL, 1974), and for an effect of lithium on sodium distribution in the kidney (Jenner & MacNeil, in press).…”

Section: Introduction Methodsmentioning

confidence: 99%

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Lithium and the antidiuretic hormone.

MacNeil¹,

Jennings²,

Eastwood³

et al. 1976

Brit J Clinical Pharma

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1The effect of lithium on the urine concentrating response to antidiuretic hormone (ADH) and the excretion of ADH has been studied in rats and man. 2 The maximum urine osmolarity following 18 h dehydration and Pitressin (5 u) was decreased in three out of four patients during lithium treatment compared to their response to the same test in the absence of lithium. In a fifth patient, tested only during lithium treatment, the urine remained hypotonic to plasma throughout this test. 3 Lithium increased the excretion of ADH in non-polyuric patients from 9-22 mu/24 h in the absence of lithium to 36-202 mu/24 h during lithium treatment. 4 In four patients with lithium-induced polyuria, a diuretic acting on the distal tubules, clorexolone, reduced the polyuria. 5 Lithium increased urine volume and the excretion of ADH in four rats receiving lithium in their diet. The response to exogenous ADH was decreased during lithium administration.

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“…The latter is well recognised in the literature (Thomsen, 1970;Singer et al, 1972;Forrest et al, 1974).…”

Section: Discussionmentioning

confidence: 84%

Section: Introduction Methodsmentioning

confidence: 99%

Lithium and the antidiuretic hormone.

MacNeil¹,

Jennings²,

Eastwood³

et al. 1976

Brit J Clinical Pharma

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“…1C). Although overall health in rats on Li diet is normal (Cappeliez, 1986;Laursen et al, 2004), rats do display polydypsia/polyurea, accompanied by sodium wasting (Lee et al, 1971;Singer et al, 1972). Therefore, all cages were equipped with a bottle of 450 mM NaCl solution, in addition to ample drinking water.…”

Section: Treatment and Health Maintenancementioning

confidence: 99%

Lithium Administration to Preadolescent Rats Causes Long-Lasting Increases in Anxiety-Like Behavior and Has Molecular Consequences

Youngs¹,

Chu²,

Meloni³

et al. 2006

J. Neurosci.

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Lithium (Li) is frequently used in the treatment of bipolar disorder (BPD), a debilitating condition that is increasingly diagnosed in children and adolescents. Because the symptoms of BPD in children are different from the typical symptoms in adulthood and have significant overlap with other childhood psychiatric disorders, this disorder is notoriously difficult to diagnose. This raises the possibility that some children not affected by BPD are treated with Li during key periods of brain development. The objective of this investigation was to examine the long-term effects of Li on the developing brain via a series of behavioral and molecular studies in rats. Rat pups were reared on Li chow for 3 weeks. Parallel groups were tested while on Li chow or 2 and 6 weeks after discontinuation of treatment. We found increased measures of anxiety-like behavior at all times tested. Gene microarray studies of the amygdala revealed that Li affected the expression of gene transcripts of the synapse and the cytoskeleton, suggesting that the treatment induced synaptic adjustments. Our study indicates that Li can alter the trajectory of brain development. Although the effects of Li on the normal brain seems unfavorable, effects on the abnormal brain cannot be determined from these studies alone and may well be therapeutic. Our results indicate that Li administration to the normal brain has the potential for lasting adverse effects.

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“…Several reports have described a reversible polyuria unresponsive to vasopressin in patients receiving lithium (5-7). Lithium has been reported to inhibit the antidiuresis normally produced by vasopressin in water-loaded rats (8), to inhibit various effects of vasopressin and 3'5' cyclic AMP in toad urinary bladders (7)(8)(9)(10), and to interfere with the stimulation of adenyl cyclase by vasopressin in rabbit and human renal medullary tissue (11)(12). We report here a series of investigations on the effects of lithium on the renal concentrating mechanism of man and the rat.…”

Section: Introductionmentioning

confidence: 99%

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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Lithium-induced nephrogenic diabetes insipidus: in vivo and in vitro studies

Cited by 178 publications

References 18 publications

Lithium and the antidiuretic hormone.

Lithium and the antidiuretic hormone.

Lithium Administration to Preadolescent Rats Causes Long-Lasting Increases in Anxiety-Like Behavior and Has Molecular Consequences

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

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