Abstract P234: Pre- And Post-treatment Analysis Of Pendrin In The Urinary Exosome In Primary Aldosteronism

Abstract

Background and Aim: Pendrin is a Cl/HCO3 exchanger that is selectively present at the apical membrane in non-α intercalated cells of the renal tubules in the kidney. Besides its role in acid/base homeostasis, accumulating studies provided evidence that pendrin regulates extracellular fluid volume and electrolyte balance. Experimental studies using animal models also indicate that pendrin is upregulated in a high aldosterone state, along with the induction of NaCl cotransporter and epithelial Na channel. However, the regulation of pendrin in human is unclear. The present study was conducted to examine the levels of pendrin in subjects with primary aldosteronism. Methods: Sixteen patients who were diagnosed as primary aldosteronism at Teikyo University Hospital and Yokohama Rosai Hospital were enrolled in this study. We isolated exosomes from pre- and post-treatment urine samples by the ultracentrifugation method, and the levels of pendrin was evaluated by Western blotting. The loading amount was adjusted by creatinine concentration. Purification of exosomal fraction was confirmed by electron microscopy and also by the presence of alix, a marker of exosome. Results and Discussion: Among 16 patients, six received unilateral adrenalectomy and 10 received MR antagonist as the treatment. Mean aldosterone-to renin ratio was 1085. We excluded two subjects because alix was not detected in the pre-treatment samples, and the analysis was done in 14 subjects. In human urine, pendrin was detected at ~110kDa and ~220kDa, the latter likely representing a dimer. We found that pendrin abundance was significantly reduced by 49.8% (P<0.01) in post-treatment samples compared with pre-treatment samples. Therefore, pendrin is altered in primary aldosteronism, likely contributing to the pathophysiology of aldosterone excess in humans.