Successful Treatment of Lithium-Induced Nephrogenic Diabetes Insipidus with Celecoxib: A Promising Therapeutic Option.

BACKGROUND Nephrogenic diabetic insipidus (NDI) poses a challenge in clinical management, particularly when associated with lithium ingestion. Non-selective non-steroidal anti-inflammatory drugs (NSAIDs) have been widely used for the treatment of numerous diseases worldwide, including NDI. However, many studies have reported the diverse adverse effects of long-term use of non-selective NSAIDs. Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is a better drug to relieve pain and inflammation in terms of long-term safety and efficacy than non-selective NSAIDs. Nevertheless, there are few reports describing the effectiveness of celecoxib in treating NDI. CASE REPORT We report a case of a 46-year-old woman with schizophrenia who presented with severe hypernatremia and refractory polyuria due to lithium-induced NDI. Cessation of lithium ingestion and traditional treatments, including trichlormethiazide and desmopressin, yielded minimal improvement in her hypernatremia and polyuria. Her sodium level needed to be strictly controlled with the infusion of dextrose 5% in water. Given the safety of celecoxib, we decided to initiate celecoxib as the treatment of lithium-induced NDI instead of indomethacin. Notably, the introduction of celecoxib led to a substantial and sustained amelioration of polyuria and hypernatremia without any celecoxib-associated adverse effects. Even after transfer to another hospital, stability in serum sodium levels persisted with celecoxib. CONCLUSIONS We presented a case of lithium-induced NDI successfully treated with celecoxib, a selective COX-2 inhibitor. To the best of our knowledge, this is the first reported case of successful treatment of lithium-induced NDI with celecoxib, and suggests celecoxib is a viable therapeutic option warranting further exploration. Physicians should consider its use when faced with the challenging management of lithium-induced NDI.

[Lithium-induced nephrogenic diabetes insipidus during acute intoxication: a case report]. / Diabète insipide néphrogénique induit par le lithium au cours d'une intoxication aiguë: à propos d'un cas.

In case of dehydration, lithium can cause acute intoxication. This picture is mainly manifested by neurological disorders that can go as far as coma, digestive disorders, hydroelectrolytic disorders, and cardiovascular disorders. We report the case of a patient followed for bipolar disorder for 20 years and treated with lithium for 14 years and who presented an acute lithium intoxication resulting from a diabetes insipidus. Our objective is to underline the importance of good hydration and strict monitoring of lithium levels especially in situations favouring dehydration, notably the polyuria of diabetes insipidus.

Metabolic reprogramming of renal epithelial cells contributes to lithium-induced nephrogenic diabetes insipidus.

Lithium, mainstay treatment for bipolar disorder, frequently causes nephrogenic diabetes insipidus (NDI) and renal injury. However, the detailed mechanism remains unclear. Here we used the analysis of metabolomics and transcriptomics and metabolic intervention in a lithium-induced NDI model. Mice were treated with lithium chloride (40 mmol/kg chow) and rotenone (ROT, 100 ppm) in diet for 28 days. Transmission electron microscopy showed extensive mitochondrial structural abnormalities in whole nephron. ROT treatment markedly ameliorated lithium-induced NDI and mitochondrial structural abnormalities. Moreover, ROT attenuated the decrease of mitochondrial membrane potential in line with the upregulation of mitochondrial genes in kidney. Metabolomics and transcriptomics data demonstrated that lithium activated galactose metabolism, glycolysis, and amino sugar and nucleotide sugar metabolism. All these events were indicative of metabolic reprogramming in kidney cells. Importantly, ROT ameliorated metabolic reprogramming in NDI model. Based on transcriptomics analysis, we also found the activation of MAPK, mTOR and PI3K-Akt signaling pathways and impaired focal adhesion, ECM-receptor interaction and actin cytoskeleton in Li-NDI model were inhibited or attenuated by ROT treatment. Meanwhile, ROT administration inhibited the increase of Reactive Oxygen Species (ROS) in NDI kidneys along with enhanced SOD2 expression. Finally, we observed that ROT partially restored the reduced AQP2 and enhanced urinary sodium excretion along with the blockade of increased PGE2 output. Taken together, the current study demonstrates that mitochondrial abnormalities and metabolic reprogramming play a key role in lithium-induced NDI, as well as the dysregulated signaling pathways, thereby serving as a novel therapeutic target.

Iatrogenic endocrine complications of lithium therapy.

Lithium is a cation, similar to sodium and potassium, affecting ion transport. It is used in the medical field as a treatment of bipolar disorders. The main endocrine complications of lithium treatment affect thyroid and parathyroid glands, in association with renal complications. Thyroid adverse effects, which are more frequent in women, comprise hypothyroidism, goiter, or sometimes hyperthyroidism, through interference with the iodine symporter. The increase in thyroid volume is early. Prevalence of goiter is 4 times higher than in the general population and hypothyroidism (8-20%) more frequent in case of pre-existing thyroid autoimmunity. Hyperthyroidism likely to worsen mood is reported in 5% of cases but the causal link to lithium is unproven. An increase in serum calcium and PTH occurs in 30% of cases, as lithium stimulates parathyroid cell proliferation by activating the Wnt pathway. The risk of hyperparathyroidism, by adenoma and especially by hyperplasia, is 5 times higher than in the general population, with the particularity of frequent low urine calcium by action on the calcium-sensing receptor (CaSR). Renal complications include risk of acute or chronic renal failure and nephrogenic diabetes insipidus, which is a factor for hypernatremia and hypercalcemia through dehydration. Nephrogenic diabetes insipidus is not always reversible after lithium therapy discontinuation. Metabolically, weight gain can be observed, but rather less than with other psychotropic drugs, and lithium does not in itself induce diabetes. At pituitary level, corticotropic activation is frequent, but implicating the disease rather than lithium. Lithium treatment induces little or no hyperprolactinemia. Regular monitoring of serum calcium, the ionogram, creatinine and TSH is recommended in lithium treatment.

Central Diabetes Insipidus in the Background of Lithium Use: Consider Central Causes Despite Nephrogenic as the Most Common.

BACKGROUND Nephrogenic diabetes insipidus is a well-known adverse effect of lithium use. Albeit rare, there have also been documented cases of central diabetes insipidus (CDI) associated with lithium use. CASE REPORT A 31-year-old woman with a past medical history of bipolar disorder, managed with lithium 300 mg by mouth every day for 3 years, was assessed for a 1-year history of polyuria with accompanying polydipsia. During her initial hospital stay, her estimated urine output was more than 4 L per day. Initial labs showed elevated serum sodium (149 mmol/L; reference range 135-145), elevated serum osmolality (304 mOsm/kg; reference range 275-295), urine osmolality of 99 mOsm/kg (reference range 50-1200), and urine specific gravity (1.005; reference range 1.005-1.030). Lithium was at a subtherapeutic level of 0.05 mEq/L (reference range 0.6-1.2). Magnetic resonance imaging of the brain revealed no abnormalities of the pituitary gland. Two different occasions of desmopressin administration resulted in >50% increase in urine osmolality, confirming the diagnosis of CDI. Common causes of CDI, including trauma, tumors, and familial CDI, were ruled out and chronic lithium use was determined as the most probable cause for the patient's CDI. CONCLUSIONS CDI in the background of chronic lithium use is rarely reported. We present this case to consider CDI as a differential diagnosis when evaluating polyuria and hypernatremia in patients with long-term lithium use. These presentations warrant the consideration of both types of diabetes insipidus in the differential diagnoses.

Psychotropic Drugs and Adverse Kidney Effects: A Systematic Review of the Past Decade of Research.

BACKGROUND AND OBJECTIVE: Psychotropic drugs are a heterogenous group of treatments prescribed for many psychiatric disorders, often for long periods. Their effects on the kidney and its functioning are complex and a source of significant research and debate. This article aims to review recent evidence of the acute and chronic kidney adverse events of diverse psychotropes. METHODS: A systematic search of randomized controlled trials and large observational studies (n ≥ 100) reporting the effects of psychotropic drugs on the kidney was conducted. The MEDLINE, PsycInfo, and EMBASE databases from 2011 to 2021, inclusive, were broadly searched with few restrictions and no prespecified outcomes. Two or more independent reviewers assessed and summarized all eligible studies, including risks of bias and levels of evidence. RESULTS: In all, 1999 abstracts were screened for eligibility and 47 articles were included, which examined lithium (33), antiepileptics (10), antipsychotics (13), and antidepressants (9). No studies examining kidney adverse effects of other psychotropes, such as benzodiazepines, met inclusion criteria. Study populations were adult (8), geriatric (9), and mixed (30). Lithium was almost unanimously associated with (1) chronic kidney disease and (2) nephrogenic diabetes insipidus in methodologically diverse studies. The most supported risk factors for declining kidney functioning with lithium were advanced age, duration of lithium treatment, acute lithium toxicity, female sex, medications with known renal interactions, diabetes mellitus/hyperglycemia, and overall medical comorbidity. Supratherapeutic lithium concentrations are both the causes and consequences of acute kidney injury. Once significant chronic kidney disease has developed, four studies found that replacing lithium with other mood stabilizers does not slow progression, and the evolution to end-stage kidney disease is rare overall with modern practices. Compared to lithium, fewer studies examined antipsychotics and antiepileptics but found relatively less direct kidney harms. Antidepressants were not associated with acute or chronic kidney harms. CONCLUSIONS: Despite the heterogeneity of findings, owing to varying methodologies and research challenges, recent studies strongly suggest that lithium is associated with an increased risk of chronic kidney disease and nephrogenic diabetes insipidus, especially in older adults and long-term lithium users. Clinicians should balance the harms of lithium against its established benefits, and ensure adequate monitoring and management of comorbidities in all patients. Weaker evidence suggests that antiepileptics such as valproate and antipsychotics result in comparatively less harm to the kidney than lithium, but warrant monitoring because of multiple direct and indirect mechanisms for potential kidney adverse events. Antidepressants do not have clear kidney adverse effects and appear safe (though potentially less effective) in the setting of kidney disease. Other classes of psychotropic drugs have received little research interest. Further research is warranted, particularly into specific antiepileptics and antipsychotics, and careful attention should be paid to mitigating important sources of bias such as confounding by indication.

What an endocrinologist should know for patients receiving lithium therapy.

Lithium is an efficient treatment of bipolar disorder. Besides renal insufficiency, many endocrine side effects are described such as the occurrence of thyroid disorders, hypercalcaemia and nephrogenic diabetes insipidus. Lithium inhibits the secretion of thyroid hormones. The prevalence of goiter is 4 times more common in Lithium-treated patients compared as to the general population. Hypothyroidism (8-20%) is more frequent in women and in case of pre-existing thyroid autoimmunity. Grave's disease and other hyperthyroidisms are sometimes reported. Lithium stimulates the proliferation of parathyroid cells by activating the Wnt pathway. An increase in serum calcium and PTH is described in patients treated with Lithium with a 4 to 6-fold higher risk of primary hyperparathyroidism than in the general population. Nevertheless, 24-hour urine calcium is not often increased, and the phenotype can mimic a hypercalcemia-hypocalciuria syndrome that may regress with Lithium discontinuation. Surgery should be cautious since parathyroid hyperplasia is more common than parathyroid adenoma. Nephrogenic diabetes insipidus is frequently reported and may be debilitating, sometimes intricated with severe dehydration, hypernatremia, and acute renal insufficiency. Nephrogenic diabetes insipidus is not generally reversible after Lithium discontinuation, especially in patients who have chronic kidney disease due to interstitial tubule nephritis. In conclusion, clinical assessment (goiter, diuresis) and biological monitoring of serum calcium, sodium creatinine, TSH and lithium are recommended in patients receiving Lithium therapy. The risk of Lithium discontinuation in case of side effects should be weighed against the psychological risk, and must be discussed with the psychiatrist.

Lithium and endocrine dysfunction.

Lithium carbonate is a commonly prescribed drug for bipolar disorders. In addition to its action on the central nervous system, lithium has systemic effects on multiple organs such as kidney, heart, motor end plate, thyroid and parathyroid glands. It can cause hypothyroidism, hyperthyroidism, goiter and ophthalmopathy by different mechanisms. It increases intrathyroid iodine content or compete for iodine transport, resulting in low iodine uptake by the thyroid. It also inhibits the coupling of iodotyrosine residues to form iodothyronines and inhibits the release of T4 and T3. Lithium has direct actions on parathyroid glands by antagonizing the calcium sensing receptor, which may induce hypercalcemia or even hyperparathyroidism, requiring surgery in some cases. Furthermore, it inhibits the expression of aquaporins, mainly aquaporin 2, in the renal collecting tubule by unknown mechanisms leading to nephrogenic diabetes insipidus. This adverse effect is usually reversible after drug withdrawal. However, some patients may present irreversible kidney damage due to chronic interstitial nephropathy.

El carbonato de litio es un fármaco que se prescribe comúnmente para el tratamiento de trastornos bipolares. Además de su acción sobre el sistema nervioso central, el litio tiene repercusiones sistémicas, afectando a múltiples órganos como el riñón, el corazón, la placa motora terminal y glándulas tiroides y paratiroides. Puede causar hipotiroidismo, hipertiroidismo, bocio y oftalmopatía por diferentes mecanismos; también aumentar el contenido de yodo intratiroideo o competir por el transporte de yodo, lo que resulta en una baja captación tiroidea de yodo. Inhibe el acoplamiento de residuos de yodotirosina para formar yodotironinas e inhibe la liberación de T4 y T3. Tiene acciones directas sobre las glándulas paratiroides antagonizando el receptor sensor de calcio, lo que puede inducir hipercalcemia e incluso hiperparatiroidismo, y puede requerir cirugía en algunos casos. Inhibe la expresión de acuaporinas en el túbulo colector renal, principalmente acuaporina 2, por mecanismos que aún no se conocen, produciendo diabetes insípida nefrogénica; este efecto adverso suele ser reversible tras la suspensión del fármaco. Sin embargo, algunos pacientes pueden presentar daño renal irreversible por nefropatía intersticial crónica.

Venous thromboembolism and severe hypernatremia in a patient with lithium-induced nephrogenic diabetes insipidus and acute kidney injury: a case report.

We report a case of thromboembolism in a patient with hypernatremia resulting from lithium-induced nephrogenic diabetes insipidus (NDI). A 49-year-old female patient on chronic lithium therapy due to bipolar disorder was transferred to the emergency department with signs of dehydration, altered mental status, and increased oxygen demand. She was admitted to a local psychiatric clinic first because of an exacerbation of a manic episode. When she was transferred to our clinic, her blood pressure was 130/80 mmHg, she was tachycardic (110 beats/min), had tachypnea (24 breaths/min), normal body temperature (36.5 ℃), and an oxygen saturation of 94% via a face mask (10 L/min). Laboratory results showed hypertonic hypernatremia (osmolality, 363 mOsm/kg; sodium, 171 mEq/L), low urine osmolality (osmolality, 231 mOsm/kg), and normal urine sodium (Na, 63 mEq/L). Her serum lithium concentration was above the therapeutic range (1.52 mmol/L). An increase in cardiac markers and changes in electrocardiogram were detected; therefore, echocardiography was performed, which showed right ventricular dysfunction and small left ventricular chamber size. Computed tomography of the chest and lower extremities showed pulmonary thromboembolism (PTE) and deep venous thrombosis (DVT). She was treated with hypotonic fluid to correct hypernatremia and intravenous heparin for thromboembolism. The size of the thromboembolism decreased, and hypernatremia was corrected. She was discharged with a direct oral anticoagulant (DOAC). Here, we report a case of severe hypernatremia and venous thromboembolism in lithium-induced NDI.

The cascade to a serendipitous discovery of lithium-induced nephrogenic diabetes insipidus.

Lithium therapy is a common treatment for affective disorders and is widely regarded as a lifesaving drug. However, because its elimination is almost wholly unchanged via the kidneys, both acute and long-term adverse effects relating to toxicity may occur, including declining renal function and nephrogenic diabetes insipidus (DI). DI may be difficult to detect and is frequently preceded by dehydration and which, in our patient, was discovered by chance. We describe a case of an elderly woman on chronic lithium therapy for bipolar affective disorder who initially presented with dehydration from vomiting but possibly developed extra-pontine myelinolysis (EPM) after over-zealous correction of hyponatraemia. Steroids administered appeared to have prevented further progression but a persisting hyperosmolar state then alerted us to the presence of nephrogenic DI. Although both conditions were later successfully reversed with no obvious chronic sequelae, the recovery of the patient was protracted. Clinicians should be vigilant for complications of managing dehydration states in people prescribed with lithium.

Protective effect of metformin on lithium-induced nephrogenic diabetes insipidus: An experimental study in rats.

BACKGROUND: Lithium is widely used in the treatment of bipolar disorders and may lead to nephrogenic diabetes insipidus (NDI), following long-term treatment. Metformin is considered the preferred initial therapy for patients with type 2 diabetes mellitus (T2D). OBJECTIVES: To investigate the protective effect of metformin on the kidney damage caused by lithium administration. MATERIAL AND METHODS: Using an animal model of chronic lithium-induced NDI, rats were divided into 4 groups: sham, metformin, lithium, and lithium + metformin. The effects of these treatments were examined using serum electrolytes, blood and tissue total antioxidant status, total oxidant status, the oxidative stress index, urine and blood osmolality, and tissue aquaporin-2 (AQP2) levels. Additionally, histopathological changes, including congestion, hydropic swelling, tubular necrosis, tubular atrophy, and Bowman's capsule dilatation, were evaluated. The total histopathological score was obtained by summing the scores for each pathological finding. RESULTS: In the lithium group, biochemical variables indicating NDI, including sodium, chloride and blood osmolality, increased, and urine osmolality decreased, compared to the sham group. With metformin treatment, the blood osmolality decreased from 328.17 mOsm/kg to 306.33 mOsm/kg, and urine osmolality increased from 349.67 mOsm/kg to 754.50 mOsm/kg (p = 0.004 and p = 0.001, respectively). Tissue AQP2 levels decreased with lithium administration but stabilized with metformin treatment. Additionally, in comparison to the lithium group, the total histopathological score in the metformin group declined from 8.0 to 2.0 (p = 0.002). CONCLUSIONS: Metformin may help protect the kidneys from lithium-induced NDI through the AQP2 regulating effect and a reduction in oxidative stress.

Genetic background determines renal response to chronic lithium treatment in female mice.

Chronic lithium treatment for bipolar disease causes mainly side effects in the kidney. A subset of lithium users develops nephrogenic diabetes insipidus (NDI), a urinary concentrating disorder, and chronic kidney disease (CKD). Age, lithium dose, and duration of treatment are important risk factors, whereas genetic background might also play an important role. To investigate the role of genetics, female mice of 29 different inbred strains were treated for 1 year with control or lithium chow and urine, blood, and kidneys were analyzed. Chronic lithium treatment increased urine production and/or reduced urine osmolality in 21 strains. Renal histology showed that lithium increased interstitial fibrosis and/or tubular atrophy in eight strains, whereas in none of the strains glomerular injury was induced. Interestingly, lithium did not elevate urinary albumin-creatinine ratio (ACR) in any strain, whereas eight strains even demonstrated a lowered ACR. The protective effect on ACR coincided with a similar decrease in urinary IgG levels, a marker of glomerular function, whereas the adverse effect of lithium on interstitial fibrosis/tubular atrophy coincided with a severe increase in urinary ß2-microglobulin (ß2M) levels, an indicator of proximal tubule damage. Genetic background plays an important role in the development of lithium-induced NDI and chronic renal pathology in female mice. The strong correlation of renal pathology with urinary ß2M levels indicates that ß2M is a promising biomarker for chronic renal damage induced by lithium.

A double-blind, randomized, placebo-controlled pilot trial of atorvastatin for nephrogenic diabetes insipidus in lithium users.

OBJECTIVE: Lithium remains an important treatment for mood disorders but is associated with kidney disease. Nephrogenic diabetes insipidus (NDI) is associated with up to 3-fold risk of incident chronic kidney disease among lithium users. There are limited randomized controlled trials (RCT) for treatments of lithium-induced NDI, and existing therapies can be poorly tolerated. Therefore, novel treatments are needed for lithium-induced NDI. METHOD: We conducted a 12-week double-blind pilot RCT to assess the feasibility and efficacy of 20 mg/d atorvastatin vs placebo in the treatment of NDI in chronic lithium users. Patients, recruited between September 2017 and October 2018, were aged 18 to 85, currently on a stable dose of lithium, and determined to have NDI. RESULTS: Urinary osmolality (UOsm) at 12 weeks adjusted for baseline was not statistically different between groups (+39.6 mOsm/kg [95% CI, -35.3, 114.5] in atorvastatin compared to placebo groups). Secondary outcomes of fluid intake and aquaporin-2 excretions at 12 weeks adjusted for baseline were -0.13 L [95% CI, -0.54, 0.28] and 98.68 [95% CI, -190.34, 387.70], respectively. A moderate effect size was observed for improvements in baseline UOsm by ≥100 mOsm/kg at 12 weeks in patients who received atorvastatin compared to placebo (38.45% (10/26) vs 22.58% (7/31); Cohen's d = 0.66). CONCLUSION: Among lithium users with NDI, atorvastatin 20 mg/d did not significantly improve urinary osmolality compared to placebo over a 12-week period. Larger confirmatory trials with longer follow-up periods may help to further assess the effects of statins on NDI, especially within patients with more severe NDI.

Triamterene in lithium-induced nephrogenic diabetes insipidus: a case report.

Lithium-induced nephrogenic diabetes insipidus (NDI) is a rare and difficult-to-treat condition. We describe the case of an 81-year-old woman with bipolar treated with lithium and no previous history of diabetes insipidus. She was hospitalized due to disturbance of consciousness and was diagnosed with, hypercalcemia, hyperparathyroidism, and NDI. Parathyroidectomy was contraindicated and parathyroid hormone level was improved insufficiently after cinacalcet initiation, percutaneous ethanol injection therapy was performed for the enlarged parathyroid gland. After improvement in hypercalcemia and unsuccessful indapamide treatment, triamterene was administrated to control polyuria. Lithium is one of the indispensable maintenance treatment options for bipolar disorder, but it has the side effect of NDI. Lithium enters the collecting duct's principal cells mainly via the epithelial sodium channel (ENaC) located on their apical membranes, ENaC shows high selectivity for both sodium and lithium, is upregulated by aldosterone, and inhibited by triamterene. To our knowledge, this is the first publication on triamterene use in lithium-induced NDI patients.

Lithium, an old friend and a forgotten enemy.

INTRODUCTION: Nephrogenic diabetes insipidus (DI) is a polyuric and polydipsic syndrome and can have multiple causing factors. CASE DESCRIPTION: A 69-year-old woman with bipolar disorder medicated with lithium 400mg for 12 years on a daily basis. The patient was admitted, after psychiatric decompensation, with hypernatremia unresponsive to hypotonic iv fluids. The diagnosis of DI was made with high plasmatic osmolality measurement, low urine osmolality, and high levels of antidiuretic hormone. Full clinical recovery was possible with lithium suspension, hydration, and chlorthalidone. DISCUSSION: Although frequently used in the past, Lithium (Li) is nowadays rarely used in clinical practice for prolonged treatments because of its potentially devastating side effects. Clinicians must be aware of those side effects in order to prevent organ damage, mainly in patients with severe bipolar disease and precarious response to alternative treatments.

Lithium, an old friend and a forgotten enemy

SUMMARY INTRODUCTION: Nephrogenic diabetes insipidus (DI) is a polyuric and polydipsic syndrome and can have multiple causing factors. CASE DESCRIPTION: A 69-year-old woman with bipolar disorder medicated with lithium 400mg for 12 years on a daily basis. The patient was admitted, after psychiatric decompensation, with hypernatremia unresponsive to hypotonic iv fluids. The diagnosis of DI was made with high plasmatic osmolality measurement, low urine osmolality, and high levels of antidiuretic hormone. Full clinical recovery was possible with lithium suspension, hydration, and chlorthalidone. DISCUSSION: Although frequently used in the past, Lithium (Li) is nowadays rarely used in clinical practice for prolonged treatments because of its potentially devastating side effects. Clinicians must be aware of those side effects in order to prevent organ damage, mainly in patients with severe bipolar disease and precarious response to alternative treatments.

RESUMO INTRODUÇÃO: O diabetes insípido nefrogênico faz parte das síndromes poliúricas polidipsicas e pode ter múltiplos fatores causais. CASO CLÍNICO: Mulher de 69 anos, com doença bipolar medicada com lítio 400 mg por dia durante 12 anos. A doente foi internada, após descompensação da doença bipolar, por hipernatremia não responsiva a fluidoterapia hipotônica endovenosa. O diagnóstico de DI foi realizado com base na elevação da osmolaridade plasmática, baixa osmolaridade urinária e níveis elevados de hormona antidiurética. Verificou-se recuperação clínica completa com suspensão do lítio, hidratação e clorotalidona. DISCUSSÃO: Apesar do seu uso frequente no passado, o lítio (Li) é hoje em dia raramente utilizado na prática clínica por períodos prolongados pelos seus efeitos potencialmente devastadores. Os médicos devem ter em conta os potenciais efeitos secundários de forma a prevenir lesão de órgão em doentes com doença bipolar de difícil controle com outra terapêutica.

[Water, lithium and sodium: watch out for dangerous injuries]. / Histoire d'eau : le lithium et le sodium, les lésions dangereuses.

Nephrogenic diabetes insipidus due to the inability of the kidneys to concentrate urine is frequently observed during lithium therapy. Lithium concentrates into principal cells in collecting ducts in the kidney and downregulates aquaporin 2 expression, which reduces renal reabsorption of water. This disease is characterized by polyuria - polydipsia leading to intracellular dehydration and hypernatremia. Water deprivation test is performed to confirm insipidus diabetes. The desmopressin permits to distinguish nephrogenic from cranial insipidus diabetes. We report the case of a 64 years old women who presented with global dehydration and severe hypernatremia. Four years ago, she was hospitalized for nephrogenic diabetes insipidus related to a self-induced lithium intoxication. Persistent nephrogenic insipidus diabetes after cessation of lithium therapy are described in literature, and this hypothesis may be consistent with this case report.