Although no changes in renal function have been noticed, we observed an enlargement of the tubulointerstitial compartment associated with histological alterations. Further, we analyzed the expression of two fibrous ECM components and infiltrating ED1 cells. We observed increased renal expression of both ECM markers and ED1 positive cells in VDD, IRI and VDD+IRI groups. Moreover, Nutlin-3 vitamin D deficiency enhanced the respective expressions of fibronectin, type IV collagen and ED1 cells. Several studies have shown that the factors of initial injury to renal cell lead to: vascular damage, including platelet aggregation and cytokine release; activation of inflammatory responses with recruitment of neutrophils and monocytes, with subsequent pro-inflammatory cytokines releasing; and fibrotic process, including pro-fibrogenic cytokine releasing such as TGF-b and CTGF by macrophages and apoptotic parenchymal cells and activation of collagen-producing cells, among others. These factors of initial injury can be initiated by many insults to the kidney, including toxic, ischemic, endocrine, infectious and immunological diseases. In our case, we must consider two main conditions: endocrine and ischemia/reperfusion insult. As a matter of fact, our results showed morphological alterations associated with increased expression of fibrous ECM components and macrophages, including those observed in VDD group even without ischemic kidney injury. Regardless of the initial insult, CKD is characterized by stereotyped kidney injury responses seen pathologically as interstitial fibrosis, tubular atrophy, peritubular capillary rarefaction, inflammation and glomerulosclerosis. Moreover, pathologic deposition of fibrillar collagenous matrix, i.e., fibrosis, results when tissues are damaged and normal wound-healing response persist or become dysregulated, usually in response to sustained or repetitive injury. Therefore, our results allow us to infer that our VDD, IRI and VDD+IRI groups were under hemodynamic and hormonal conditions that contributed to the morphological changes found in the renal tissues. Attempting to establish a link between fibrosis formation and vitamin D deficiency, we evaluated the expressions of TGF-b and VDR in IRI and VDD+IRI groups, both with more prominent interstitial expansion. We observed that vitamin D deficiency caused a decrease in VDR expression and an increase in TGF-b expression in VDD+IRI group, which had the highest ratio of fibrosis. Thus, our data allowed us to infer that adequate levels of vitamin D could help to slow the renal fibrosis formation. In 2006 Tan 6et al, using the vitamin D analogue paricalcitol in a model of obstructive nephropathy, showed that paricalcitol treatment was able to suppress the expressions of TGF-b and its respective receptor. In addition, paricalcitol treatment restored the expression of VDR receptor, blocked the epithelial-mesenchymal transition, and inhibited cell apoptosis and proliferation.