Identification of the Causes for Chronic Hypokalemia: Importance of Urinary Sodium and Chloride Excretion

Am J Med. 2017 Jul;130(7):846-855. doi: 10.1016/j.amjmed.2017.01.023. Epub 2017 Feb 14.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Anorexia; Bulimia; Diuretics; Electrolytes; Hypokalemia; Laxatives; Urine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acidosis, Renal Tubular / complications
  • Acidosis, Renal Tubular / diagnosis
  • Adult
  • Anorexia Nervosa / complications
  • Anorexia Nervosa / diagnosis
  • Bartter Syndrome / complications
  • Bartter Syndrome / diagnosis
  • Body Mass Index
  • Bulimia / complications
  • Bulimia / diagnosis
  • Chlorides / urine
  • Chronic Disease
  • Diuretics / adverse effects
  • Female
  • Gitelman Syndrome / complications
  • Gitelman Syndrome / diagnosis
  • Humans
  • Hypokalemia / etiology*
  • Hypokalemia / urine
  • Laxatives / adverse effects
  • Male
  • Prospective Studies
  • Sex Factors
  • Sodium / urine
  • Substance-Related Disorders / complications
  • Substance-Related Disorders / diagnosis

Substances

  • Chlorides
  • Diuretics
  • Laxatives
  • Sodium