Fanconi syndrome, diabetes insipidus, and acute kidney injury due to tenofovir disoproxil fumarate: A case report.

BACKGROUND: Tenofovir disoproxil fumarate is widely used in Botswana as part of the first-line antiretroviral regimen in the 'Treat All' strategy implemented in 2016 by the Ministry of Health. Its use has been associated with several uncommon adverse renal effects, though rarely all in conjunction or without the combined use of protease inhibitors. CASE PRESENTATION: A 49-year-old woman living with HIV whose viral load is suppressed on tenofovir disoproxil fumarate, lamivudine, and dolutegravir presented with 1 day of generalized weakness and myalgia causing an inability to ambulate. This was associated with nausea and vomiting and profound fatigue. She was found to have an acute kidney injury, non-anion-gap metabolic acidosis, hypernatremia, hypokalemia, and hypophosphatemia. Urinalysis revealed pyuria with white blood cell casts, glucosuria, and proteinuria. The diagnosis was made of tenofovir-induced nephrotoxicity. The tenofovir was discontinued, and the patient was initiated on intravenous fluids and electrolyte and bicarbonate supplementation with improvement in her symptoms and laboratory values. CONCLUSIONS: This report suggests the possibility of severe tenofovir-induced nephrotoxicity with combined acute kidney injury, Fanconi syndrome, and nephrogenic diabetes insipidus in the absence of other provoking factors such as use with protease inhibitors or advanced HIV disease, chronic kidney disease, and age. With its wide use in Botswana and other countries, health-care providers should have a high index of suspicion for tenofovir-induced nephrotoxicity for HIV patients on tenofovir with deranged renal function tests and electrolytes.

Diabetes insipidus related to sedation in the intensive care unit: A review of the literature.

PURPOSE: To identify cases of diabetes insipidus (DI) related to sedation in the ICU to determine which medications pose the greatest risk and understand patterns of presentation. MATERIALS AND METHODS: We searched PubMed, Embase, Scopus, Google Scholar, and Web of Science. Search terms included "polyuria," "diabetes insipidus," "hypnotics and sedatives," "sedation," as well as individual medications. Case reports or series involving DI or polyuria related to sedation in the ICU were identified. RESULTS: We identified 21 cases of diabetes insipidus or polyuria in the ICU attributed to a sedative. Dexmedetomidine was implicated in 42.9% of cases, followed by sevoflurane (33.3%) and ketamine (23.8%). Sevoflurane was implicated in all 7 cases in which it was used (100%; 95% CI 59.0%, 100.0%), dexmedetomidine in 9 of 11 cases (81.8%; 95% CI 48.2, 97.7), and ketamine in 5 of 9 cases (55.6%; 95% CI 21.2%, 86.3%). CONCLUSIONS: Awareness of the potential for sedatives to cause DI may lead to greater identification with swifter medication discontinuation and subsequent resolution of DI.

Probable Dexmedetomidine Induced Diabetes Insipidus: A Case Review.

What is known and objective: Despite increased use of dexmedetomidine as a light sedative in the ICU setting, diabetes insipidus (DI) secondary to a dexmedetomidine infusion has rarely been reported. Case summary: We present a 32-year-old male admitted to the surgical intensive care unit (ICU) with 50% total body surface area burn. A short time following initiation (0.2 mcg/kg/hr) and up-titration (0.8 mcg/kg/hr) of dexmedetomidine continuous infusion, the patient developed DI, eventually exceeding 3 L of urine within a 6-hour timeframe. Excessive polyuria also led to significant electrolyte shifts (serum sodium 156 mmol/L and serum potassium < 1.8 mmol/L), resulting in Torsade's de Pointes. What is new and conclusion: Our case discusses diabetes insipidus leading to severe electrolyte abnormalities secondary to dexmedetomidine.

Dexmedetomidine-associated diabetes insipidus during skull base surgery in a pediatric patient.

Diabetes insipidus is characterized by polyuria due to an inability to auto-regulate water balance resulting in dangerous metabolic derangements. Intraoperative anesthetics have been increasingly identified as a cause of diabetes insipidus in adult patients; however, it is rare in pediatrics. We present a case of a 16-year-old male undergoing resection of a recurrent left juvenile nasopharyngeal angiofibroma who experienced intraoperative polyuria concerning diabetes insipidus. Urine output drastically decreased following discontinuation of dexmedetomidine with complete resolution within 24 h. We conclude that this case of transient diabetes insipidus was associated with dexmedetomidine administration.

Concomitant neuroleptic malignant syndrome and diabetes insipidus.

ABSTRACT: Each year, nearly one-fifth of adults in the United States are prescribed at least one psychotropic medication. An increased trend in psychiatric polypharmacy has heightened awareness of drug-drug interactions and the tracking of adverse drug reactions. This article describes a patient who developed concomitant neuroleptic malignant syndrome (NMS) and nephrogenic diabetes insipidus during cross-titration of his antipsychotics while on lithium. The patient's mild form of NMS in turn caused hypovolemia and acute kidney injury. This case study highlights the dangers of polypharmacy and how it can obscure the presentation of even classic adverse reactions.

[Renal toxicity of lithium]. / Néphrotoxicité du lithium.

Besides its efficiency, lithium has a narrow therapeutic index and can result in considerable toxicity. Among the potential side effects, two types of renal toxicity are observed: a decreased renal concentrating ability and a chronic renal failure. Lithium-induced polyuria is frequent, estimated to affect up to 40% of patients, and develops usually early. It may be irreversible, especially if the treatment has been prescribed for more than 15 years. A chronic renal failure is observed in patients treated for more than 10 to 20 years. Its prevalence is estimated at 12% after 19 years of treatment. Some patients (0.5%) may reach end stage renal disease. The major risk factor is the duration of exposure to lithium. Discussion about stopping or not lithium in case of renal failure needs multidisciplinary expertise and depends on psychiatric status and renal function.

Ketamine-Induced Diabetes Insipidus.

The authors report a case of diabetes insipidus (DI) associated with a ketamine infusion. A 42-year-old Asian man underwent an exploratory laparotomy and splenectomy who was admitted to the surgical intensive care unit (ICU) for postoperative management. Pain control was attempted with escalating dose of opioids but was inadequate, prompting the addition of a ketamine infusion. Shortly after initiation, a massive rise in urine output ensued in addition to a change in his urine electrolyte studies, leading to the diagnosis of drug-induced diabetes insipidus. Ketamine was discontinued, and treatment with subcutaneous desmopressin was initiated. Treatment was continued for a total of 5 days, which resulted in a resolution of his DI. This report suggests that the patient likely experienced a medication-induced DI, which was successfully resolved through proper identification of the causative agent, removal, and subsequent treatment with desmopressin. Causality assessment between ketamine and DI was determined using the Naranjo Adverse Drug Reaction Probability Scale-a total score of 7 was achieved and thus identified the adverse drug reaction as probable. Clinicians should be aware of the possibility that ketamine may be contributory in a patient with unexplained DI.

Transient Diabetes Insipidus After Discontinuation of Vasopressin in Neurological Intensive Care Unit Patients: Case Series and Literature Review.

BACKGROUND: Arginine vasopressin (AVP) is a common second-line or third-line vasopressor used in critically ill neurosurgical patients. Neurosurgical indications include hyperdynamic therapy for vasospasm, maintenance of cerebral perfusion pressure in patients with intracranial hypertension, and prevention of hypotension in patients with sepsis. CASE DESCRIPTION: A series of 6 neurosurgical patients receiving AVP infusions developed severe but transient diabetes insipidus (tDI) after cessation of AVP. To our knowledge, no previous reports of this phenomenon in neurosurgical patients have been published. We reviewed the clinical histories, intensive care unit treatment, medication administration records, and laboratory values of these patients, and we found recurrent elevated serum sodium and urine output and decreased urine specific gravity after discontinuation of AVP. Resolution of tDI occurred upon resumption of AVP or administration of desmopressin. Elevated serum sodium levels were often severe, resulting in worsened clinical outcomes. When AVP was resumed, tDI typically recurred if AVP was again tapered and discontinued. Routine administration of desmopressin was useful in controlling sodium levels until the tDI resolved. CONCLUSIONS: Recognition of this phenomenon has caused us to change our clinical management of neurosurgical patients receiving AVP. We hypothesize that tDI is caused by downregulation of the V2 receptor mass in the renal distal convoluted tubule and collecting duct cells. When AVP is discontinued, patients develop nephrogenic tDI secondary to decreased V2 receptor binding, which explains why desmopressin is effective in correcting tDI. Future research includes a large prospective study to determine risk factors for tDI, its incidence, and its pathophysiology.

Intractable Polyuria Mimicking Diabetes Insipidus-Source Traced to Vecuronium Infusion.

Continuous infusion of vecuronium is a commonly used technique for patients requiring prolonged neuromuscular blockade for mechanical ventilation. As compared with older neuromuscular blocking agents, it confers the advantages of rapid excretion and intermediate duration of action. Prolongation of neuromuscular blockade and muscle weakness are the known complications of continuous vecuronium infusion. This report attempts to describe polyuria, as a hitherto unknown complication of vecuronium infusion, which can occur due to the mannitol present in commercially available preparation of vecuronium bromide.

Propofol and diabetes insipidus.

A case in which the intraoperative administration of propofol was strongly associated with an acute episode of diabetes insipidus is presented.

Transient central diabetes insipidus induced by ketamine infusion.

OBJECTIVE: Report a case of central diabetes insipidus (DI) associated with ketamine infusion. CASE SUMMARY: A 2-year-old girl with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency and stable hypertrophic cardiomyopathy was admitted to the pediatric intensive care with pneumonia. She subsequently developed respiratory failure and required intubation. Continuous ketamine infusion was used for the sedation and facilitation of mechanical ventilation. Shortly after infusion of ketamine, the patient developed DI and responded appropriately to vasopressin. DISCUSSION: The Naranjo adverse drug reaction probability scale indicated a probable relationship between the development of central DI and ketamine. The most likely mechanism involves ketamine's antagonist action on N-methyl-d-aspartate receptors, resulting in inhibition of glutamate-stimulated arginine vasopressin release from the neurohypophysis. CONCLUSION: This is the second case report of ketamine-induced central DI and the only report in children. Clinicians who sedate children with continuous ketamine infusions should monitor patients for developing signs and symptoms of DI by measuring serum sodium and urine output prior to, during, and after ketamine infusion in order to make a timely diagnosis of this potentially serious complication.

Is environmental temperature related to renal symptoms, serum lithium levels, and other laboratory test results in current lithium users?

OBJECTIVE: Lithium continues to be an important mood disorder treatment. Although patients exposed to higher environmental temperatures may have serum lithium level elevations due to dehydration, there is conflicting data in the literature. In addition, no study has assessed the association between temperature and other renal laboratory tests and symptoms in lithium users. METHODS: This is a cross-sectional analysis of 63 current lithium users who participated in the McGill Geriatric Lithium-induced Diabetes Insipidus Clinical Study. The relationship between mean daily temperature with diabetes insipidus symptoms, glomerular filtration rate, urine osmolality, serum sodium, lithium level, and lithium dose-level ratio was assessed. RESULTS: Although a higher temperature on the day of laboratory testing trended toward being independently associated with a lower lithium dose-level ratio (Beta = -0.17, p = 0.08), this was not found when using a dichotomous measure of temperature (T > 20°C). No association was observed between temperature and other renal parameters. CONCLUSIONS: The association of temperature with lithium levels, renal symptoms, and laboratory tests appears to be of relatively little clinical importance in lithium users in temperate climates. However, future research should re-examine patients living in climates with extreme temperatures (e.g., >40°C), who may theoretically be at higher risk.

Ifosfamide-induced Fanconi syndrome with diabetes insipidus.

Ifosfamide-induced Fanconi syndrome is a rare complication that typically occurs in young patients due to a cumulative dose of ifosfamide > 40-60 g/m(2), a reduction in kidney mass, or concurrent cisplatin treatment. It is usually characterized by severe and fatal progression accompanied by type II proximal renal tubular dysfunction, as evidenced by glycosuria, proteinuria, electrolyte loss, and metabolic acidosis. Diabetes insipidus is also a rare complication of ifosfamide-induced renal disease. We herein describe a case involving a 61-year-old man who developed ifosfamide-induced Fanconi syndrome accompanied by diabetes insipidus only a few days after the first round of chemotherapy. He had no known risk factors. In addition, we briefly review the mechanisms and possible therapeutic options for this condition based on other cases in the literature. Patients who receive ifosfamide must be closely monitored for renal impairment to avoid this rare but fatal complication.

[The effect of long-term lithium treatment on kidney function]. / Wplyw dlugotrwalego podawania litu na czynnosc nerek.

In 1963 it was first demonstrated that long-term lithium administration exerts a "mood-stabilising" effect, preventing recurrences of mania and depression in bipolar affective disorder. Despite the introduction of many other drugs having mood-stabilising effect, lithium still remains the first choice drug for the prophylaxis of affective episodes in mood disorder. Lithium is eliminated nearly exclusively by the kidneys: lithium clearance is proportional to creatinine clearance and is influenced by natriuretic and antinatriuretic factors. Nowadays, nearly 40-year experience with long-term lithium treatment point to a possibility of nephrotoxic effects of this ion. Impaired urinary concentrating ability, which, in a few patients can reach an intensity of diabetes insipidus, can occur after several weeks of lithium administration. Favourable results in the treatment of diabetes insipidus have been obtained with amiloride, the drug which block epithelial sodium channel. However, after 10-20 years of treatment, lithium-induced interstitial nephropathy may be demonstrated in some patients, which, in small proportion of the latter may lead to end-stage renal disease. Lithium-induced hipercalcemia and nephrotic syndrome are rare complications of lithium therapy. In patients on long-term lithium therapy periodic monitoring of kidney function by measuring serum creatinine concentration and glomerular filtration rate is necessary. In case of detecting nephropathy, a discontinuation of lithium sho uld be considered. The patient in whom lithium was discontinued due to nephropathy should remain in nephrological treatment.