Beyond the transtubular potassium gradient: Alternative urinary markers for diagnosing hypoaldosteronism

The transtubular potassium gradient (TTKG) is a widely accepted tool for assessing mineralocorticoid activity in hyperkalemia. However, its clinical utility is often limited due to the unavailability of urine osmolality. Identifying alternative, more accessible urinary indices could improve diagnostic performance in suspected hypoaldosteronism.

We conducted a retrospective observational study including 106 hyperkalemic patients with hypoaldosteronism referred to Endocrinology Department. Through correlation analyses using Spearman's ρ and Pearson's r, we assessed the relationship between TTKG values and the urinary potassium-to-serum potassium ratio (UK⁺/SK⁺), the urinary potassium-to-creatinine ratio (UK⁺/creatinine), the fractional excretion of potassium (FEK), and the urinary sodium-to-potassium ratio (UNa⁺/UK).

Mean age, 74±12 years; mean TTKG, 3.8±1.2, and UK⁺/creatinine, 62±28mmol/g. Median UNa⁺/UK⁺, 2.78 [1.81-3.72]; UK⁺/SK⁺, 5.1 [4-6.8]; FEK, 12.9% [7-18.9]. TTKG showed a strong positive correlation with UK⁺/SK⁺ (ρ=0.706; p<0.001) and FEK (ρ=0.585; p<0.001), and a moderate correlation with UK⁺/creatinine (r=0.352; p=0.011). An inverse strong correlation was observed with UNa⁺/UK⁺ (ρ=-0.655; p<0.001).

UK⁺/SK, UK⁺/creatinine, FEK, and UNa⁺/UK⁺ seem to be practical alternatives for assessing renal potassium excretion in hyperkalemia associated with hypoaldosteronism. Further studies are warranted to validate these findings in larger and diverse cohorts.