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

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.