International Scholarly Research Network ISRN Oncology Volume 2012, Article ID 798239, 10 pages doi:10.5402/2012/798239 Clinical Study Assessment of Ondansetron-Associated Hypokalemia in Pediatric Oncology Patients Elsa Fiedrich, Vikram Sabhaney, Justin Lui, and Maury Pinsk Division of Pediatric Nephrology, University of Alberta, 11405-87 Avenue, Edmonton, AB, Canada T6G 1C9 Correspondence should be addressed to Maury Pinsk, mpinsk@ualberta.ca Received 4 July 2012; Accepted 14 August 2012 Academic Editors: Z. Estrov and L. Mutti Copyright © 2012 Elsa Fiedrich et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objectives. Ondansetron is a 5-hydroxytryptamine (5-HT 3 , serotonin) receptor antagonist used as antiemetic prophylaxis preceding chemotherapy administration. Hypokalemia is a rare complication of ondansetron, which may be underreported due to confounding emesis and chemotherapy-induced tubulopathy. We performed a prospective cohort study to determine if ondansetron caused significant hypokalemia independently as a result of renal potassium wasting. Methods. Twelve patients were recruited, with ten completing the study. Blood and urine samples were collected before and after ondansetron administration in patients admitted for intravenous (IV) hydration and chemotherapy. Dietary histories and IV records were analyzed to calculate sodium and potassium balances. Results. We observed an expected drop in urine osmolality, an increase in urine sodium, but no statistically significant change in sodium or potassium balance before and after ondansetron. Conclusion. Ondansetron does not cause significant potassium wasting in appropriately hydrated and nutritionally replete patients. Careful monitoring of serum potassium is recommended in patients with chronic nutritional or volume status deficiencies receiving this medication. 1. Introduction Ondansetron is an antiemetic used as an adjunctive to chemotherapy in pediatric oncology patients. It is a selec- tive 5-HT 3 receptor antagonist which has an excellent safety profile and is efficacious [1, 2]. A side effect infre- quently reported is the development of hypokalemia [3]. Hypokalemia may be a result of ondansetron itself [3–5], an effect of chemotherapy on renal tubular function [6], a result of emesis-induced alkalosis [7], or a combination of factors. Based on in vitro data, ondansetron has the capacity to cause hypokalemia by affecting renal tubular physiology [4]. Ondansetron acts at two levels in the nephron. First, at the level of the Loop of Henle, ondansetron downregulates the Na + -K + -2Cl-(NKCC2) cotransporter, which results in increased sodium delivery to the distal nephron. This in turn necessitates K + excretion, via the ROMK potassium channel to facilitate the electroneutral reabsorption of sodium via the epithelial sodium channel (ENaC) from the distal nephron, leading to K + wasting. Second, throughout the nephron, and in particular the distal tubule, ondansetron upregulates the Na + -K + ATPase. This exacerbates the renal K wasting by lowering intracellular sodium levels in distal tubular cells expressing ENaC thereby further increasing tubular sodium entry at this segment. This ultimately requires increased K secretion into the urine via ROMK to maintain electroneutrality. Based on in vitro data, this effect on the renal tubules appears specific to ondansetron and is not a characteristic of other selective 5-HT 3 antagonists [8]. We previously described an association between ondansetron use and the reproducible development of hypokalemia in a pediatric oncology patient [5]. On review, ondansetron was recognized as a potential causative agent. Within 24 hours of discontinuation of ondansetron, the patient’s potassium level and transtubular potassium gradient (TTKG) returned to acceptable levels. The patient was readmitted one month later for IV cyclophosphamide therapy, and a single dose of ondansetron was administered as standard anti-emetic prophylaxis. The TTKG rose to an inappropriately high level has given the patient’s volume status, with a concurrent drop in the patient’s plasma potassium level.