Aquaporin-2 in the early stages of the adenine-induced chronic kidney disease model

Abstract

Chronic kidney disease (CKD) is one of the leading health problems in the world. It is silentin the early stages and gradually progresses, inducing renal physiological and structuralalterations. Moreover, CKD is associated with impaired life quality, increased risk for cardiovascular diseases, and reduced life expectancy. Different CKD animal models differ inunderlying etiology, time of onset, and associated diseases. The 0.25% adenine dietinduces progressive kidney damage, constituting an adequate model mimicking humanCKD. Vasopressin (VP) was postulated as a mediator of CKD, mainly acting through its V2receptors. However, the molecular mechanisms involved in the pathogenesis of this condition and its progression still are not entirely understood. This study aimed to evaluate ifAQP2 expression is altered in an adenine-induced model of CKD in rats at early stages ofdevelopment (two weeks) and to assess a potential beneficial effect of Tolvaptan (a V2receptor antagonist) treatment. We showed an increased renal medullary AQP2 expressionat two weeks of adenine administration. This increase was mainly cytoplasmic, explainingthe increased urinary volume of CKD rats and suggesting a possible non-canonical role forAQP2. In addition, Tolvaptan effectively inhibited the V2 receptor in both control and CKDrats, decreasing AQP2 expression and increasing diuresis. Moreover, Tolvaptan slightlyreduced BUN and plasma creatinine. On the other hand, the renal alterations induced byadenine in CKD rats were not prevented by Tolvaptan.