This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/nep.12929 This article is protected by copyright. All rights reserved. Amiloride modifies the progression of lithium-induced renal interstitial fibrosis. Running title: Amiloride and lithium-induced chronic interstitial fibrosis PRIYAKSHI KALITA-DE CROFT 1,2 , JENNIFER J BEDFORD 1 , JOHN P LEADER 1 , and ROBERT J WALKER 1 Departments of Medicine 1 and Physiology 2 , University of Otago, P.O. Box 913, Dunedin, New Zealand. Corresponding author: Professor Robert Walker, Department of Medicine, University of Otago, P.O. Box 913, Dunedin, New Zealand rob.walker@otago.ac.nz ABSTRACT: Aim: Long-term administration of lithium has been associated with the development of a chronic interstitial fibrosis in addition to nephrogenic diabetes insipidus (NDI). Earlier studies have demonstrated that amiloride, by blocking the epithelial sodium channel ENaC and thus preventing lithium uptake into the principal cells of the collecting ducts, can partially reverse lithium-induced NDI. However, there are no long-term studies examining whether or not amiloride also modifies the progressive chronic interstitial fibrosis and tubular atrophy often evident with long term lithium exposure.