Evaluation of the events involved in the renal changes associated with experimental models of ischemic acute kidney injury, 5/6 nephrectomy and nephrotoxicity by Amphotericin B: influence of vitamin D deficiency

Abstract

Ischemia/reperfusion (I/R) is the main cause of acute kidney injury (AKI). The pathophysiology of injury from I/R involves a complex exchange among renal hemodynamics, tubular injury and inflammation, as well as active process of proliferation and cell death. This complex interaction among vascular factors, tubular and inflammatory are usually followed by a repair process that can restore function and epithelial differentiation or result in chronic kidney disease (CKD) with gradual onset of fibrosis and subsequent progression to end-stage kidney disease. It has been demonstrated that the mortality of patients with CKD, besides being related to renal function, is also due to cardiovascular diseases and infections. Among the many kinds of infections, invasive fungal infections (IFI) are a major cause of morbidity and mortality in those immunocompromised or hospitalized patients with serious diseases. However, traditional hazards such as cardiovascular diseases and infections account for only half of the causes of mortality of patients with renal disease. Currently, several studies are being directed to non-traditional risk factors, such as vitamin D deficiency. The aim of this work is to evaluate the events involved in the renal changes associated with experimental models of ischemic AKI, 5/6 nephrectomy and nephrotoxicity by Amphotericin B in influence of vitamin D. Wistar rats will be subjected to surgical induction of I/R to obtain the AKI model (protocol 1), and to 5/6 nephrectomy model of CKD ( Protocol 2). The third protocol involves the use of nephrotoxicity model by amphotericin B. All animal protocols involve control and vitamin D deficient animals. We will evaluate kidney function, biochemical parameters (electrolytes, proteinuria, hormones), and hemodynamics (renal blood flow and blood pressure). Furthermore, experiments will be conducted to study the renal microvasculature, immunohistochemical studies (inflammation pathways phenotypic change, conveyors) and histomorphometry (renal injury, interstitial area and on glomerular area), protein analysis (carriers, and vascular factors growth, receivers) and evaluation of gene expression (analysis of the renin-angiotensin-system, vitamin D receptor and Klotho). (AU)