Elevated direct bilirubin: Possible predictors for pseudoaldosteronism: Case–control study

Abstract

ABSTRACTAimPseudoaldosteronism is a known side‐effect of licorice, and Japanese traditional Kampo medicine is one of the major areas of use of licorice in Japan. Multidrug resistance protein 2 (Mrp2) dysfunction is important for pseudoaldosteronism. Congenital deficiency of Mrp2 causes constitutional jaundice with elevated direct bilirubin. Hence, elevated direct bilirubin can be a biomarker of Mrp2 dysfunction. The relationship between pseudoaldosteronism and elevated direct bilirubin, however, has not been studied as yet. The aim of the present study was therefore to evaluate the relationship between elevated direct bilirubin and hypokalemia, an important characteristic of pseudoaldosteronism.MethodsThis retrospective observational study included patients who first visited the Kampo Clinic at Keio University Hospital between May 2008 and March 2015. Inclusion criteria were Kampo formulas including licorice prescribed for >2 weeks, and availability of laboratory data on direct bilirubin and change in serum potassium.ResultsData from 243 patients (57 men, 186 women) were used in the analysis. Mean age was 52.0 ± 16.2 years. Hypokalemia was noted in three patients (1.3%), among whom elevated direct bilirubin was noted in two (0.9%). The remaining patient with hypokalemia was diagnosed with pseudo‐Bartter's syndrome because of loop diuretic use. The remaining 240 patients had neither hypokalemia nor elevated direct bilirubin ( P = 0.0001, Fisher's exact test).ConclusionElevated direct bilirubin is an important predictor of pseudoaldosteronism.