title: Identification of the Causes for Chronic Hypokalemia: Importance of Urinary Sodium and Chloride Excretion.
abstract: Uncovering the correct diagnosis of chronic hypokalemia with potassium (K+) wasting from the kidneys or gut can be fraught with challenges. We identified clinical and laboratory parameters helpful for differentiating the causes of chronic hypokalemia.
  
  
  
  Normotensive patients referred to our tertiary academic medical center for the evaluation of chronic hypokalemia were prospectively enrolled over 5 years. Clinical features, laboratory examinations-including blood and spot urine electrolytes, acid-base status, biochemistries, and hormones-as well as genetic analysis, were determined.
  
  
  
  Ninety-nine patients with chronic normotensive hypokalemia (serum K+2.8 ± 0.4 mmol/L, duration 4.1 ± 0.9 years) were enrolled. Neuromuscular symptoms were the most common complaints. Although Gitelman syndrome (n = 33), Bartter syndrome (n = 10), and distal renal tubular acidosis (n = 12) were the predominant renal tubular disorders, 44 patients (44%) were diagnosed with anorexia/bulimia nervosa (n = 21), surreptitious use of laxatives (n = 11), or diuretics (n = 12). Patients with gastrointestinal causes and surreptitious diuretics use exhibited a female predominance, lower body mass index, and less K+supplementation. High urine K+excretion (transtubular potassium gradient >3, urine K+/Cr >2 mmol/mmol) was universally present in patients with renal tubular disorders, but also found in >50% patients with gastrointestinal causes. Of interest, while urine sodium (Na+) and chloride (Cl-) excretions were high and coupled (urine Na+/Cl-ratio ∼1) in renal tubular disorders and "on" diuretics use, skewed or uncoupled urine Na+and Cl-excretions were found in anorexia/bulimia nervosa and laxatives abuse (urine Na+/Cl-ratio: 5.0 ± 2.2, 0.4 ± 0.2, respectively) and low urine Na+and Cl-excretions with fixed Na+/Cl-ratios (0.9 ± 0.2) when "off" diuretics.
  
  
  
  Besides body mass index, sex, and blood acid-base status, integrated interpretation of the urine Na+:Cl-excretion and their ratio is important to make an accurate diagnosis and treatment plan for patients with chronic normotensive hypokalemia.
authors.affiliation: Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Department of Medicine, Armed Forces Taoyuan General Hospital, Taoyuan, Taiwan.
authors.forename: Kun-Lin
authors.initials: KL
authors.lastname: Wu
authors.affiliation: Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Chih-Jen
authors.initials: CJ
authors.lastname: Cheng
authors.affiliation: Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Chih-Chen
authors.initials: CC
authors.lastname: Sung
authors.affiliation: Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan; Division of Pediatric Nephrology, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Tseng
authors.affiliation: Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yu-Juei
authors.initials: YJ
authors.lastname: Hsu
authors.affiliation: Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Sung-Sen
authors.initials: SS
authors.lastname: Yang
authors.affiliation: Department of Medicine, Providence St. Vincent Medical Center, Portland, Ore.
authors.forename: Tom
authors.initials: T
authors.lastname: Chau
authors.affiliation: Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan. Electronic address: l521116@ndmctsgh.edu.tw.
authors.forename: Shih-Hua
authors.initials: SH
authors.lastname: Lin
mesh_terms: D000141:Acidosis, Renal Tubular / Q000150:complications / Q000175:diagnosis; D000328:Adult; D000856:Anorexia Nervosa / Q000150:complications / Q000175:diagnosis; D001477:Bartter Syndrome / Q000150:complications / Q000175:diagnosis; D015992:Body Mass Index; D002032:Bulimia / Q000150:complications / Q000175:diagnosis; D002712:Chlorides / Q000652:urine; D002908:Chronic Disease; D004232:Diuretics / Q000009:adverse effects; D005260:Female; D053579:Gitelman Syndrome / Q000150:complications / Q000175:diagnosis; D006801:Humans; D007008:Hypokalemia / Q000209:etiology* / Q000652:urine; D054368:Laxatives / Q000009:adverse effects; D008297:Male; D011446:Prospective Studies; D012737:Sex Factors; D012964:Sodium / Q000652:urine; D019966:Substance-Related Disorders / Q000150:complications / Q000175:diagnosis
chemical_list: D002712:Chlorides; D004232:Diuretics; D054368:Laxatives; D012964:Sodium
keywords: Anorexia; Bulimia; Diuretics; Electrolytes; Hypokalemia; Laxatives; Urine