Study of vitamin D replacement in the evolution of ischemic acute kidney injury in vitamin D deficient rats

Abstract

Acute kidney injury (AKI) alters renal hemodynamics, leads to tubular injury, activates inflammation pathways, proliferation, and cell death. The initial damage caused in renal tissue after an ischemia/reperfusion (I/R) event suggests an important role in the pathogenesis of AKI course. Likewise, the establishment of the disease may lead to predisposition to chronic kidney disease (CKD). Vitamin D deficiency (dVD) is associated with tubulointerstitial damage and progression of I/R-AKI. On the other hand, vitamin D may be considered a protective factor. Thus, the purpose of this study is to verify the effect of vitamin D replacement in the evolution of ischemic acute kidney injury in vitamin D deficient rats. Wistar rats will be divided into three groups: I/R, will receive a standard diet for 120 days and I/R surgery will be performed on day 30; I/R dVD, will receive vitamin D free diet for 120 days and I/R surgery will be performed on day 30; and I/R RVD, will receive vitamin D free diet for the first 30 days and I/R surgery will be performed on day 30. In the last 90 days, vitamin D free diet will be replaced by the standard diet (vitamin D replacement). Functional parameters (renal function), biochemical (electrolytes, proteinuria, hormones), and hemodynamics (renal flow and blood pressure) will be evaluated. In addition, immunohistochemical (pathways of inflammation, phenotypic alteration and transporters) and histomorphometric (renal lesions and relative interstitial area) studies, protein analysis (transporters, vascular and growth factors, receptors) and evaluation of gene expression renin-angiotensin system, vitamin D receptor and Klotho) will be performed. (AU)