Investigating the role of urinary electrolyte parameters in the differential diagnosis of hypokalemia

Hypokalemia is a common clinical electrolyte disorder. In normotensive patients with renal potassium (K⁺) wasting, distinguishing vomiting-related upper gastrointestinal (UGI) disorders from renal tubular diseases (RTDs), including Gitelman syndrome (GS) and distal renal tubular acidosis (dRTA), is challenging due to overlapping manifestations. Assessment based on isolated urinary potassium excretion has limited diagnostic value.

We retrospectively analyzed 86 normotensive hypokalemic patients with inappropriate renal K⁺ loss admitted to our department (2016 - 2025), divided into the UGI group (n = 25, vomiting-related) and RTD group (n = 61: 34GS, 27dRTA). Clinical characteristics and blood/urine biochemical parameters were systematically collected. The spot urine K⁺/creatinine (Cr) ratio, fractional excretion of electrolytes (FEK, FENa, FECl), and blood/urine Na⁺/Cl^- ratios were calculated. Between-group comparisons and ROC curve analysis were performed.

Compared with the RTD group, the UGI group had a significantly higher female proportion, lower BMI, shorter duration of hypokalemia-related symptoms, marked hypochloremia, hyponatremia, severe metabolic alkalosis, and elevated serum Cr and uric acid (UA) (all p < 0.05). Spot urine analysis showed higher Na⁺, lower Cl^-, and elevated Na⁺/Cl^- and FENa/FECl ratios, whereas spot urine K⁺/Cr ratio and FEK did not differ significantly between groups. ROC analysis demonstrated that spot urine Cl^- had the highest diagnostic accuracy for vomiting-induced hypokalemia (AUC 0.978; cutoff < 33.3 mmol/L, sensitivity 92%, specificity 95.1%). Urine Na⁺/Cl^- and FENa/FECl ratios also achieved excellent performance (both AUC 0.965). Notably, serum Cl^- also showed favorable diagnostic performance (AUC 0.939) with a cutoff of < 94.9 mmol/L.

Vomiting-related UGI disorders and RTDs both cause normotensive hypokalemia with renal K⁺ wasting. Notably, vomiting-related UGI disorders predominantly affect females with lower BMI and may be complicated by prerenal acute kidney injury (AKI). Serum Cl^- measurement serves as a valuable initial screening tool for suspected UGI disorders. Urinary K⁺ excretion markers have limited diagnostic value, and comprehensive urinary electrolyte analysis is required. Among all evaluated parameters, spot urine Cl^- concentration demonstrates the highest diagnostic performance.