Background: Urinary concentration impairment is a major feature of cyclosporine nephrotoxicity. Methods: We explored two possible mechanisms that may underlie cyclosporine-induced polyuria; water, and/or osmotic diuresis. Cyclosporine was subcutaneously injected to normal salt-fed Sprague-Dawley rats at a daily dose of 25 mg/kg for 2 weeks (Experiment I) and 7.5 mg/kg for 6 weeks (Experiment II). Results: In Experiment I, cyclosporine treatment caused an increase in urine volume (2.7±0.5 vs. 10.3±1.13 mL/d/100 g BW, p<0.001) and a decrease in urine osmolality (2,831±554 vs. 1,379±478 mOsm/kg H2O, p<0.05). Aquaporin-2 (AQP2) protein ex-pression decreased in cyclosporine-treated rat kidneys (cortex, 78±8%, p<0.05;medulla, 80±1%, p<0.05). Experiment II also showed that urine volume was incre-ased by cyclosporine treatment (4.97±0.66 vs. 9.65±1.76 mL/d/100 g BW, p<0.05).Whereas urine osmolality was not affected, urinary excretion of osmoles was in-creased (7.5±0.4 vs. 14.9±1.4 mosmoles/d/100 g BW, p<0.005). Notably, urinary excretion of glucose increased in cyclosporine-treated rats (7±1 vs. 10,932±2,462mg/d/100 g BW, p<0.005) without a significant elevation in plasma glucose. In both Experiment I and II, GLUT2 protein expression in the renal cortex was decre-ased by cyclosporine treatment (Experiment I, 55±6%, p<0.005; Experiment II, 88±3%, p<0.05). Conclusion: Both water diuresis and osmotic diuresis are induced by cyclosporine nephrotoxicity. AQP2 and GLUT2 downregulation may underlie water and osmotic diuresis, respectively.

• Aquaporin-2
• Cyclosporine
• GLUT2
• Osmotic diuresis
• Water diuresis

Voriconazole is a triazole antifungal agent used to treat serious fungal infec- tions and undergoes hepatic metabolism by the cytochrome P450 system. Severe hyperkalemia was reported in a kidney transplant recipient when voriconazole and tacrolimus were coadministered. The azole antifungals may interfere with the biosynthesis of adrenal steroids and therefore can predispose patients to aldosterone deficiency. However, it is unclear whe- ther voriconazole by itself can induce hypoaldosteronism or hyperkalemia. Here, we report a case of voriconazole-induced hyperkalemia who had con- current medications to treat comorbidities. Voriconazole was orally admi- nistered for pulmonary aspergillosis, and three episodes of severe hyper- kalemia recurred and were improved by emergency treatment. At the first episode, renin-angiotensin-aldosterone system inhibitors were associated. We found that dronedarone might have increased the voriconazole level at the second episode. At this time, severe hypercalcemia was concurrent and improved by acute hemodialysis and eliminating dronedarone. Finally, severe hyperkalemia recurred without concurrent medications known to in- teract with voriconazole. We switched voriconazole into itraconazole, and his hyperkalemia was resolved. Drug level monitoring is necessary when vori- conazole is used. Genetic susceptibility such as CYP2C19 polymorphism may be investigated in patients with adverse reactions to voriconazole.

• Dronedarone
• Drug interactions
• Hypercalcemia
• Hyperkalemia
• Voriconazole

A 56-year old female patient who was undergoing follow-up for cervical cancer in our oncology center was presented to the emergency center with anxiety and excessive thirst. The initial serum sodium level of the patient exceeded 200 mEq/L, rising up to 238 mEq/L during hospitalization. The extremely severe hypernatremia was caused by patient’s wrong belief that bay salt would cure the cancer. The patient was treated with hypotonic solution and finally with appropriate hydra- tion, she was fully recovered without any neurological complications.

• Dehydration
• Hypernatremia
• Malignancy

Sjögren's syndrome (SS) is an autoimmune disease that presents with exo- crine gland dysfunction. Renal involvement is common in SS and often results in tubulointerstitial nephritis, renal tubular acidosis, and Fanconi’s syndrome. Electrolyte imbalances are commonly the first symptom of renal involvement of SS. The most common feature of dysnatremia in SS is hy- pernatremia with diabetes insipidus. However, cases of hyponatremia with syndrome of inappropriate antidiuretic hormone secretion (SIADH) are rarely reported in patients with SS. Herein, we report a case of recurrent severe SIADH in a patient with SS.

• Duloxetine hydrochloride
• Hyponatremia
• Inappropriate ADH syndrome
• Sjögren's syndrome