Lithium polyuria

In nephrogenic diabetes insipidus the kidney s ability to respond to AVP is impaired by different causes, such as drugs (e.g. lithium), chronic disorders (e.g. sickle cell disease, kidney failure) or inherited genetic disorders (X-linked or autosomal NDI). This type of diabetes insipidus can not be treated by exogenous administration of AVP or AVP analogues. Instead, diuretics (hydrochlorothiazide combined or not with amiloride) and NSAI (indomethacin) are administrated to ameliorate polyuria. 

Lithium carbonate is rapidly absorbed after oral administration. The most common adverse reactions include tremors, nausea, vomiting, thirst, and polyuria Toxic reactions may be seen when serum lithium levels are greater than 1.5 mEq/L (Table 32-1). Because some of these toxic reactions are potentially serious, lithium blood levels are usually obtained during therapy, and the dosage of lithium is adjusted according to the results. 

The answer is c. (Katzung, p 493.) Lithium treatment frequently causes polyuria and polydipsia. The collecting tubule of the kidney loses the capacity to conserve water via anti diuretic hormone. This results in significant free-water clearance, which is referred to as nephrogenic diabetes insipidus. 

Lithium reduces the kidney s ability to concentrate urine and may cause a nephrogenic diabetes insipidus with low urine specific gravity and low osmolality polyuria (urine volume greater than 3 L/day). This may be treated with loop diuretics, thiazide diuretics, or triamterene. If a thiazide diuretic is used, lithium doses should be decreased by 50% and lithium and potassium levels monitored. 

Unlabeled uses Amiloride (10 to 20 mg/day) may be useful in reducing lithium-induced polyuria without increasing lithium levels as is seen with thiazide diuretics. 

Adverse reactions that are not dose dependent are nausea, vomiting and diarrhoea. Lithium has a low therapeutic index. Some adverse reactions such as thirst and mild polyuria may occur at therapeutic plasma concentrations of 0.4-1.0 mEq/1. At concentrations of 1.0-1.6 mEq/1 diarrhea, nausea and incoordination become prominent. At toxic levels ataxia, confusion and stupor occur potentially leading to coma and death. 

Unlabeled Uses Treatment of edema associated with CHF, liver cirrhosis, and nephrotic syndrome treatment of hypertension reduces lithium-induced polyuria, slows pulmonary function reduction in cystic fibrosis... 

Polyuria, polydipsia, tremor, ataxia, nausea, diarrhea, weight gain, drowsiness, acne, hair loss Possible effects on thyroid and renal functioning with longterm administration Children prone to dehydration are at higher risk for acute lithium toxicity... 

Bersudsky Y, Vinnitsky 1, Grisaru N, et al The effect of inositol on lithium-induced polyuria-polydipsia in rats and humans. Human Psychopharmacology 7 403-407, 1992... 

Lithium Neurological tremor, ataxia, seizures Endocrine hypothyroidism Cardiovascular T wave changes, sinus node dysfunction Renal polyuria, nephrogenic diabetic insipidus Dermatological hair loss, acne, psoriasis, rash Gastrointestinal nausea, diarrhea Miscellaneous fluid retention, weight gain, weakness... 

Rosten MD, Forest JN. Treatment of severe lithium-induced polyuria with amiloride. Am J Psychiatry 1986 143 1563-1568. 

There is no final consensus on whether normal use of lithium, without any episode of toxicity (the vast majority of patients), may result in permanent renal impairment. Polyuria occurs in 20-40% and is due to inhibition of antidiuretic hormone (ADH) by lithium. It usually resolves on cessation of lithium as do any effects on glomerular function. Interference with thyroid function is due to inhibition of the action of thyroid stimulating hormone (TSH) and is easily managed by administration of thyroxine. Lithium is contraindicated during pregnancy (major vessel anomalies in fetus) and breastfeeding. 

Amiloride Blocks epithelial sodium channels in collecting tubules Reduces Na retention and wasting increases lithium clearance Hypokalemia from other diuretics reduces lithium-induced polyuria Orally active duration 24 h Toxicity Hyperkalemic metabolic acidosis... 

Because lithium affects second-messenger systems involving both activation of adenylyl cyclase and phosphoinositol turnover, it is not surprising that G proteins are also found to be affected. Several studies suggest that lithium may uncouple receptors from their G proteins indeed, two of lithium s most common side effects, polyuria and subclinical hypothyroidism, may be due to uncoupling of the vasopressin and thyroid-stimulating hormone (TSH) receptors from their G proteins. 

Polydipsia and polyuria are common but reversible concomitants of lithium treatment, occurring at therapeutic serum concentrations. The principal physiologic lesion involved is loss of responsiveness to antidiuretic hormone (nephrogenic diabetes insipidus). Lithium-induced diabetes insipidus is resistant to vasopressin but responds to amiloride. 

When a 45-year-old man with severe lithium-induced diabetes insipidus developed hyperosmolar, nonketotic hyperglycemia, it was suggested that poorly controlled diabetes mellitus may have contributed to the polyuria (684). Prior contact with a female patient who had developed hyperosmolar coma secondary to lithium-induced diabetes insipidus (685) allowed physicians 4 years later to treat her safely after a drug overdose and a surgical procedure, by avoiding intravenous replacement fluids with a high dextrose content (despite stopping lithium several years earlier, the patient continued to put out 10 liters of urine daily) (686). 

When 60 patients (22 men, 38 women) who had taken lithium for 1 year or more (mean 6.9 years mean serum concentration 0.74 mmol/1) were interviewed about adverse effects, 60% complained of polyuria-polydipsia syndrome (serum creatinine concentrations were normal) and 27% had hypothyroidism requiring treatment (108). Weight gain was more common in women (47 versus 18%) as were hypothyroidism (37 versus 9%) and skin problems (16 versus 9%), while tremor was more common in men (54 versus 26%). Weight gain of over 5 kg in the first year of treatment was the only independent variable predictive of hypothyroidism. 

Long-term use of lithium is sometimes associated with weight gain, polyuria and polydipsia, and thyroid dysfunction (see below), but many patients have been treated successfully for several decades without developing treatment-limiting adverse effects. However, long-term success should not breed complacency, since there is an ever-present risk of recurrence (if concentrations are too low) and toxicity (if concentrations are too high). 

A comprehensive review of psychoactive drug-induced hyposalivation and hypersalivation included a discussion of lithium-induced dry mouth (common) and sialorrhea (347). A review of dental findings and their management in patients with bipolar disorder briefly mentioned that xerostomia, sialadenitis, dysgeusia, and stomatitis have been attributed to lithium (348). Dry mouth is common and can be due to lithium-induced polyuria, a direct effect on thirst, salivary gland hypofunction, or other drugs (347). Hypersalivation attributable to lithium is rare (349). 

Nephrogenic diabetes insipidus secondary to lithium led to severe dehydration in two patients who required intravenous rehydration followed by a thiazide diuretic to reduce urine volume (382). One patient had persistent polyuria (6.7 1/day) 57 months after stopping lithium (296). 

Eight years after stopping lithium because of polydipsia and polyuria, a 55-year-old woman was hospitalized with lethargy, coma, and hypernatremia (sodium concentration 156 mmol/1) after her fluid intake had been restricted (391). 

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