Physiology and pathophysiology of renal aquaporins

Søren Nielsen, Tae Hwan Kwon, Birgitte Mønster Christensen, Dominique Promeneur, Jørgen Frøkiær, David Marples

Research output: Contribution to journalArticlepeer-review

261 Scopus citations


The discovery of aquaporin membrane water channels by Agre and coworkers answered a long-standing biophysical question of how water specifically crosses biologic membranes, and provided insight, at the molecular level, into the fundamental physiology of water balance and the pathophysiology of water balance disorders. Of nine aquaporin isoforms, at least six are known to be present in the kidney at distinct sites along the nephron and collecting duct. Aquaporin-1 (aqp1) is extremely abundant in the proximal tubule and descending thin limb, where it appears to provide the chief route for proximal nephron water reabsorption. Aqp2 is abundant in the collecting duct principal cells and is the chief target for vasopressin to regulate collecting duct water reabsorption. Acute regulation involves vasopressin- regulated trafficking of Aqp2 between an intracellular reservoir and the apical plasma membrane. In addition, Aqp2 is involved in chronic/adaptational regulation of body water balance achieved through regulation of Aqp2 expression. Importantly, multiple studies have now identified a critical role of Aqp2 in several inherited and acquired water balance disorders. This concerns inherited forms of nephrogenic diabetes insipidus and several, much more common acquired types of nephrogenic diabetes insipidus where Aqp2 expression and/or targeting are affected. Conversely, Aqp2 expression and targeting appear to be increased in some conditions with water retention such as pregnancy and congestive heart failure. Aqp3 and Aqp4 are basolateral water channels located in the kidney collecting duct, and Aqp6 and Aqp7 appear to be expressed at lower abundance at several sites including the proximal tubule. This review focuses mainly on the role of Aqp2 in water balance regulation and in the pathophysiology of water balance disorders.

Original languageEnglish
Pages (from-to)647-663
Number of pages17
JournalJournal of the American Society of Nephrology : JASN
Issue number3
StatePublished - Mar 1999


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