Up Front MattersClaudins and the KidneyYu, Alan S.L. Author Information Division of Nephrology and Hypertension, and the Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas Correspondence: Dr. Alan S.L. Yu, Kidney Institute, University of Kansas Medical Center, 3901 Rainbow Boulevard, 6018 WHE, Kansas City, KS 66160-3018. Email: [email protected] Journal of the American Society of Nephrology 26(1):p 11-19, January 2015. | DOI: 10.1681/ASN.2014030284 Buy Metrics Abstract Claudins are tight-junction membrane proteins that function as both pores and barriers in the paracellular pathway in epithelial cells. In the kidney, claudins determine the permeability and selectivity of different nephron segments along the renal tubule. In the proximal tubule, claudins have a role in the bulk reabsorption of salt and water. In the thick ascending limb, claudins are important for the reabsorption of calcium and magnesium and are tightly regulated by the calcium-sensing receptor. In the distal nephron, claudins need to form cation barriers and chloride pores to facilitate electrogenic sodium reabsorption and potassium and acid secretion. Aldosterone and the with-no-lysine (WNK) proteins likely regulate claudins to fine-tune distal nephron salt transport. Genetic mutations in claudin-16 and -19 cause familial hypomagnesemic hypercalciuria with nephrocalcinosis, whereas polymorphisms in claudin-14 are associated with kidney stone risk. It is likely that additional roles for claudins in the pathogenesis of other types of kidney diseases have yet to be uncovered. Copyright © 2015 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.