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

Jorge Gabriel Ruiz-Sánchez, Alfonso Luis Calle-Pascual, Miguel Ángel Rubio-Herrera, María Paz De Miguel Novoa, Emilia Gómez-Hoyos, Isabelle Runkle

Journal: Endocrinologia, diabetes y nutricion 2026;73(3):501686

PMID: 41802899

Abstract

BACKGROUND

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.

METHODS

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).

RESULTS

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).

CONCLUSIONS

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.

Copyright © 2025 SEEN and SED. Published by Elsevier España, S.L.U. All rights reserved.

Address: Servicio de Endocrinología y Nutrición, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD, UAM), Hospital Universitario Fundación Jiménez Díaz, 28040 Madrid, Spain. Electronic address: [email protected].; Facultad de Medicina, Universidad Complutense de Madrid, 28040 Madrid, Spain; Servicio de Endocrinología y Nutrición, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Hospital Clínico San Carlos, 28040 Madrid, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), 28029 Madrid, Spain.; Facultad de Medicina, Universidad Complutense de Madrid, 28040 Madrid, Spain; Servicio de Endocrinología y Nutrición, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Hospital Clínico San Carlos, 28040 Madrid, Spain.; Servicio de Endocrinología y Nutrición, Hospital Clínico Universitario de Valladolid, 47003 Valladolid, Spain.
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