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

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.