Cell and Transport PhysiologySecretory-Defect Distal Renal Tubular Acidosis Is Associated with Transporter Defect in H+-ATPase and Anion Exchanger-1Han, Jin Suk*; Kim, Gheun-Ho†; Kim, Jin‡; Jeon, Un Sil§; Joo, Kwon Wook¶; Na, Ki Young*; Ahn, Curie*; Kim, Suhnggwon*; Lee, Sang Eun∥; Lee, Jung Sang* Author Information *Department of Internal Medicine, Seoul National University, Clinical Research Institute of Seoul National University Hospital, Seoul, Korea; †Department of Internal Medicine, Hallym University Hangang Sacred Heart Hospital, Seoul, Korea; ‡Department of Anatomy, Catholic University, Seoul, Korea; §Department of Internal Medicine, Gyeong-sang National University, Chinju, Korea; ¶Department of Internal Medicine, Gachon Medical School, Incheon, Korea; ∥Department of Urology, Seoul National University, Seoul, Korea. Correspondence to: Dr. Jung Sang Lee, Department of Internal Medicine, Seoul National University, Research Institute of Seoul National University Hospital, 28, Yongun-dong, Chongno-gu, Seoul, 110-744, South Korea. Phone: +82-2-760-2265; Fax : +82-2-742-9031; E-mail : [email protected] Accepted February 02, 2002 Received January 17, 2002 Journal of the American Society of Nephrology 13(6):p 1425-1432, June 2002. | DOI: 10.1097/01.ASN.0000013882.73122.2B Buy Metrics Abstract ABSTRACT. Recent progress in molecular physiology has permitted us to understand pathophysiology of various channelopathies at a molecular level. The secretion of H+ from α-intercalated cells is mediated by apical plasma membrane H+-ATPase and basolateral plasma membrane anion exchanger-1 (AE1). Studies have demonstrated the lack of H+-ATPase immunostaining in the intercalated cells in a few patients with distal renal tubular acidosis (dRTA). Mutations in H+-ATPase and AE1 gene have recently been reported to cause dRTA. This study extends the investigation of the role of transporter defect in dRTA by using immunohistochemical methods. Eleven patients with hyperchloremic metabolic acidosis were diagnosed functionally to have secretory-defect dRTA: urine pH >5.5 during acidemia, normokalemia or hypokalemia, and urine-to-blood pCO2 <25 mmHg during bicarbonaturia. Renal biopsy tissue was obtained from each patient, and immunohistochemistry was carried out using antibodies to H+-ATPase and AE1. For comparison, renal tissues from the patients who had no evidences of distal acidification defect by functional studies were used: four with glomerulopathy or tubulointerstitial nephritis (disease controls) and three from nephrectomized kidneys for renal cell carcinoma (normal controls). The H+-ATPase immunoreactivity in α-intercalated cells was almost absent in all of the 11 patients with secretory-defect dRTA. In addition, 7 of 11 patients with secretory-defect dRTA were accompanied by negative AE1 immunoreactivity. In both disease controls and normal controls, the immunoreactivity of H+-ATPase and AE1 was strong in α-intercalated cells. In conclusion, significant defect in acid-base transporters is the major cause of secretory-defect dRTA. Copyright © 2002 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.