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.

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.

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.

Proximal tubular dysfunction associated with tenofovir and didanosine causing Fanconi syndrome and diabetes insipidus: a report of 3 cases.

We report 3 cases of patients with HIV/AIDS in whom Fanconi syndrome and nephrogenic diabetes insipidus developed secondary to use of an antiretroviral regimen containing tenofovir disoproxil fumarate and didanosine. These patients presented with a history of polydipsia, polyuria, weight loss, anorexia, and wasting. Interestingly, 1 patient was not taking protease inhibitors. This response is a well-documented yet uncommon complication of tenofovir use in the HIV population. We recommend continued monitoring for renal toxicity when using NRTI combination of tenofovir and didanosine.

Desmopressin (dDAVP) incident signals the need for enhanced monitoring protocols.

In this article, the authors highlight the circumstances surrounding the death of a young adult neurosurgical patient, recently reported to ISMP Canada. The incident signals the need for enhanced safeguards for patients receiving desmopressin (also known as dDAVP) and intravenous therapy. The authors present information from a recent ISMP Canada Safety Bulletin relevant to critical care, including an outline of potential contributing factors and suggested recommendations.

Lithium-induced nephrogenic diabetes insipidus after coronary artery bypass.

We present a case of nephrogenic diabetes insipidus that occurred after on-pump coronary artery bypass grafting in a patient taking long-term lithium carbonate. Lithium toxicity (2.79 mmol/L) was identified on postoperative day 9. Serum sodium peaked at 175 mmol/L on postoperative day 21. Serum osmolality peaked at 384 mOsm/kg H2O, with a urinary osmolality of 403 mOsm/kg H2O. The patient was ultimately managed with hemofiltration and high-dose 1-desamino-8-D-arginine-vasopressin. Recommendations are made based on our experience of this case. In patients on long-term lithium therapy, the potentially life-threatening complication of lithium-induced nephrogenic diabetes insipidus should be specifically anticipated and managed.

Severe hypernatraemia due to nephrogenic diabetes insipidus - a life-threatening side effect of chronic lithium therapy.

Renal toxicity of long-term lithium therapy is a common problem. Nephrogenic diabetes insipidus is the most frequently encountered complication, but often remains unrecognised because of the rather benign symptoms. We present a patient with long-term lithium therapy who developed life-threatening hypernatraemia due to insufficient oral fluid intake after elective spinal surgery. Careful daily substitution of up to 25 l of hypotonic fluids led to full recovery within 9 days. Nephrogenic diabetes insipidus should always be considered in lithium-treated patients undergoing elective surgery in order to avoid severe hypernatraemia.

Lithium treatment induces a marked proliferation of primarily principal cells in rat kidney inner medullary collecting duct.

Lithium (Li) treatment for 4 wk has previously been shown to increase the fraction of intercalated cells in parallel with a decrease in the fraction of principal cells in the kidney collecting duct (Christensen BM, Marples D, Kim YH, Wang W, Frøkiaer J, and Nielsen S. Am J Physiol Cell Physiol 286: C952-C964, 2004; Kim YH, Kwon TH, Christensen BM, Nielsen J, Wall SM, Madsen KM, Frøkiaer J, and Nielsen S. Am J Physiol Renal Physiol 285: F1244-F1257, 2003). To study how early this fractional change starts, the origin of the cells and the possible mechanism behind the changes, we did time course studies in rats subjected to different durations of Li treatment (i.e., for 4, 10, and 15 days). Increased urine output was already observed at day 4 of Li treatment with decreased AQP2 levels although not statistically significant. At days 10 and 15, both a significant polyuria and downregulation in AQP2 expression were observed. At day 10, the density of H+-ATPase-positive cells was increased in the IMCD of Li-treated rats and this was further pronounced at day 15. Some of the H+-ATPase-positive cells did not costain with Cl-/HCO3- exchanger AE1, indicating that they were not fully differentiated to type A IC. By double labeling for either H+-ATPase and proliferating-cell nuclear antigen (PCNA) or for AQP4 and PCNA, we found that proliferation mainly occurred in proximal IMCD cells at day 4 and it increased toward the middle part of the IMCD in response to prolonged Li treatment. Most cells expressing PCNA were stained with AQP4 but not with H+-ATPase. Triple-labeling for H+-ATPase, AQP4, and PCNA showed a subset of cells negative for all three proteins or only positive for PCNA. In contrast, a 4-wk recovery period after 4 wk of Li treatment reversed the enhanced proliferative rate to the control levels. In conclusion, the Li-induced increase in the density of intercalated cells is associated with a high proliferative rate of principal cells in the IM-1 and IM-2 rather than a selective proliferation of intercalated cells as expected. This is likely to contribute to the remodeling of the collecting duct after Li treatment.

[Lithium, a potentially dangerous drug]. / Lithium, een potentieel gevaarlijk geneesmiddel.

Two patients with a bipolar disorder, a woman aged 56 and a woman aged 68, who had used lithium for more than 30 years, were seen with side effects from this medication. Both patients were treated by their general practitioner and had not visited a psychiatrist for many years. The first patient had a chronic lithium intoxication with cerebellar signs and eventually coma, diabetes insipidus, hyperthyroidism, hyperparathyroidism and psoriasis. After 6 weeks of treatment in the intensive-care unit she made a good recovery. The second patient had several lithium side effects. She was diagnosed with diabetes insipidus, hyperparathyroidism due to a parathyroid adenoma, hypothyroidism and a sick-sinus syndrome. A pacemaker was implanted 4 years earlier. The adenoma was surgically removed. After other medication was tried, the patient was once again given lithium, on which she was able to function well. The first patient had lithium concentrations above the therapeutic value for several years and both patients experienced a delay before their signs and symptoms were attributed to lithium. Lithium treatment should be monitored by an experienced psychiatrist.

Hydrocortisone dose and postoperative diabetes insipidus in patients undergoing transsphenoidal pituitary surgery: a prospective randomized controlled study.

We report the results of a prospective randomized controlled trial, which looked at the incidence of postoperative diabetes insipidus (DI) following the use of three different hydrocortisone protocols, and the results of a study, on the incidence of DI and cortisol response in patients not given hydrocortisone. In study 1, 114 patients with pituitary macroadenoma were randomized into three groups: conventional dose (inj. hydrocortisone 100 mg IV 6-hourly for 3 days); intermediate dose (inj. hydrocortisone 100 mg IV 6-hourly on day 1, 100 mg IV 8-hourly on day 2, and 100 mg IV 12-hourly on day 3); low dose protocol (inj. hydrocortisone 25 mg IV 6-hourly on day 1, 25 mg IV 8-hourly on day 2 and 25 mg IV 12-hourly on day 3). Radical excision was achieved in 92 patients. The incidence of DI with the conventional dose was 52%, intermediate dose, 36% and low dose, 24% (p = 0.025). Study 2 included 16 consecutive patients with Hardy's grade A & B pituitary adenoma. These patients were randomized to receive (Group I) or not receive (Group II) hydrocortisone. Patients in Group II demonstrated normal cortisol response intraoperatively and no patient developed features of hypocortisolism; the incidence of DI in this group was 14%. The low dose hydrocortisone protocol reduced the incidence of DI by 46% when compared with the conventional dose hydrocortisone protocol. In patients with grade A and B tumour with normal preoperative cortisol levels, the use of perioperative hydrocortisone can be avoided.

Altered expression of renal AQPs and Na(+) transporters in rats with lithium-induced NDI.

Lithium (Li) treatment is often associated with nephrogenic diabetes insipidus (NDI). The changes in whole kidney expression of aquaporin-1 (AQP1), -2, and -3 as well as Na-K-ATPase, type 3 Na/H exchanger (NHE3), type 2 Na-Pi cotransporter (NaPi-2), type 1 bumetanide-sensitive Na-K-2Cl cotransporter (BSC-1), and thiazide-sensitive Na-Cl cotransporter (TSC) were examined in rats treated with Li orally for 4 wk: protocol 1, high doses of Li (high Na(+) intake), and protocol 2, low doses of Li (identical food and normal Na(+) intake in Li-treated and control rats). Both protocols resulted in severe polyuria. Semiquantitative immunoblotting revealed that whole kidney abundance of AQP2 was dramatically reduced to 6% (protocol 1) and 27% (protocol 2) of control levels. In contrast, the abundance of AQP1 was not decreased. Immunoelectron microscopy confirmed the dramatic downregulation of AQP2 and AQP3, whereas AQP4 labeling was not reduced. Li-treated rats had a marked increase in urinary Na(+) excretion in both protocols. However, the expression of several major Na(+) transporters in the proximal tubule, loop of Henle, and distal convoluted tubule was unchanged in protocol 2, whereas in protocol 1 significantly increased NHE3 and BSC-1 expression or reduced NaPi-2 expression was associated with chronic Li treatment. In conclusion, severe downregulation of AQP2 and AQP3 appears to be important for the development of Li-induced polyuria. In contrast, the increased or unchanged expression of NHE3, BSC-1, Na-K-ATPase, and TSC indicates that these Na(+) transporters do not participate in the development of Li-induced polyuria.

Acute myeloid leukaemia with trilineage myelodysplasia complicated by masked diabetes insipidus.

We describe a rare case of acute myeloid leukaemia with trilineage myelodysplasia complicated by central diabetes insipidus. In the present case, diabetes insipidus was masked by corticosteroid deficiency due to hypopituitarism and clinical symptoms presented after administering methylprednisolone. Although the remission of leukaemia was not achieved by chemotherapy, excessive urinary output was well-controlled by nasal administration of 1-desamino-8-D-arginine vasopressin (DDAVP) during the course.