Cicletanine-induced hyponatremia and hypokalemia in kidney transplant patients

BACKGROUND Cicletanine is an antihypertensive agent with vasorelaxant and diuretic properties. It has been widely used in European countries; however, cicletanine-associated electrolyte disturbances have yet to be defined. We investigated cicletanine-induced hyponatremia and hypokalemia in kidney transplant patients. METHODS Data from a total of 68 kidney transplant recipients who were treated for hypertension with cicletanine were retrospectively analyzed. Cicletanine-induced hyponatremia and hypokalemia were defined as serum sodium < 135 mmol/L and potassium < 3.5 mmol/L, respectively, after the use of cicletanine. RESULTS The average patient age was 50 (±11) years, and 44 (65%) were male. The daily dose of cicletanine was 171 ± 46 mg, and the duration of drug use was 215 ± 514 days. Hyponatremia occurred in 11 patients (16.2%), and hypokalemia occurred in 8 patients (11.8%). Three patients (4.4%) had hyponatremia and hypokalemia simultaneously. The duration of cicletanine administration was significantly longer in patients with hyponatremia than in those without hyponatremia (943 ± 958 vs. 74 ± 166 days, P < 0.05). The occurrence of hypokalemia was not affected by either daily dose or duration of drug use. Among 11 patients with hyponatremia, 10 were corrected within 2 weeks after withdrawal of the drug and 1 was spontaneously corrected. Among 8 cases of hypokalemia, 7 were corrected after withdrawal of the drug and 1 was spontaneously corrected. CONCLUSION We demonstrate that cicletanine may induce hyponatremia or hypokalemia in kidney transplant patients. Hyponatremia is more frequently associated with cicletanine than hypokalemia, and extended use of cicletanine may increase the risk of hyponatremia.