Brief report Gentamicin-induced Bartter-like syndrome Daniel Landau 1 and Kanwal K. Kher 2 1 Department of Pediatrics, Soroka Medical Center and Faculty of Health Sciences Ben Gurion University in Negev, Beer Sheva, Israel 2 Department of Nephrology, Children's National Medical Center, George Washington University School of Medicine, Washington, DC 20010, USA Received December 10, 1996; received in revised form May 5, 1997; accepted May 14, 1997 Abstract. Gentamicin is well known to be associated with nephrotoxicity, including acute renal failure and renal tubular dysfunction. A Bartter-like syndrome has also been described as a toxic manifestation of gentamicin therapy in adults, but this nephrotoxic syndrome has not been well characterized in children. In this report we describe the clinical course of four patients with gentamicin-associated Bartter-like syndrome. These patients ranged in age from 4 months to 17 years; they all demonstrated evidence of renal tubulopathy, primarily affecting the distal nephron. Hypo- calcemia, hypomagnesemia, alkalosis, and hypokalemia were the main manifestations in these patients. After dis- continuation of gentamicin, recovery of the renal tubular functions and resolution of the electrolyte abnormalities were complete in all patients. Key words: Aminoglycosides ± Nephrotoxicity ± Bartter syndrome ± Bartter-like syndrome ± Tubular dysfunction ± Hypomagnesemia ± Tetany Introduction Bartter syndrome is a disorder that is characterized by hypokalemic metabolic alkalosis, hyper-reninemia, hyper- trophy of juxtaglomerular apparatus, and insensitivity to exogenous angiotensin II [1]. An inability to reabsorb chloride (Cl) in the thick ascending limb of the loop of Henle may be the primary underlying defect [2]. This has been supported by recent findings of mutations affecting the sodium (Na)/potassium (K)/Cl cotransporter in that nephron segment in patients with the antenatal variant of Bartter syndrome [3]. Mutations in other ion channel-en- coding genes have also been found in patients with Bartter syndrome and its variants [4±6]. Several clinical condi- tions, such as persistent or surreptitious vomiting and diuretic abuse, can also mimic the metabolic abnormalities seen in Bartter syndrome; these disorders are often referred to as pseudo-Bartter or Bartter-like syndromes [7, 8]. A Bartter-like syndrome has also been reported in association with aminoglycoside therapy. Most of such reported cases have been among adult patients [9±17]. To our knowledge, only two pediatric patients with Bartter-like syndrome due to gentamicin therapy have been described in the published literature [18, 19]. Our report describes the clinical course of four children who developed Bartter-like syndrome fol- lowing gentamicin therapy. Case reports Case 1 A 12-year-old, black female was hospitalized for perforated appendi- citis. Escherichia coli was cultured from the peritoneal fluid. She re- ceived intravenous antibiotic therapy consisting of gentamicin and metronidazole. The dose of gentamicin was 7.5 mg/kg per day, in three divided doses, and the cumulative dose amounted to 120 mg/kg, given over 23 days. Serum creatinine, blood urea nitrogen (BUN), electro- lytes, magnesium, and peak and trough gentamicin levels were normal during the 1st week of treatment. The patient continued to have an adequate urine output. She received intravenous hyperalimentation during her first 7 postoperative days and oral feeding thereafter. On postoperative day 24, the patient complained of dizziness, accompanied by numbness, tingling, and pain in her hands. Physical examination confirmed tetanic spasms in both hands. Although she did not manifest clinical signs of dehydration, orthostatic hypotension was documented. The laboratory evaluation (Table 1) documented normal BUN, serum creatinine, hypokalemia (K 2.2 mmol/l), hypochloremia (Cl 88 mmol/l), metabolic alkalosis [bicarbonate (HCO3) 38 mmol/l], and hypomagnesemia [magnesium (Mg) 0.33 mmol/l]. Urinary Cl excretion was elevated (Cl 166 mmol/l), ruling out the possibility of extrarenal electrolyte loss. Transtubular potassium gradient (TTKG), a measure of tubular potassium excretion 1 was elevated (14.9, age- appropriate normal mean = 6.0, range 4.1±10.5) [20]. Urinary Mg excretion was persistently elevated (Mg 30±37 mmol/l). Urinary drug screening for diuretics was negative. Fractional excretion of b2- microglobulin was normal (0.22%, normal 50.36%) [21]. Plasma Correspondence to: D. Landau, Department of Pediatrics, Soroka Medical Center, P.O. Box 151, Beer Sheva 84101, Israel Pediatr Nephrol (1997) 11: 737 ± 740 Ó IPNA 1997 1 TTKG = (urine potassium:plasma potassium)/(urine osmolality/ plasma osmolality