Abstract
BackgroundDespite a significant improvement in the management of chronic kidney disease (CKD), its incidence and prevalence has been increasing over the years. Progressive renal fibrosis is present in CKD and involves the participation of several cytokines, including Transforming growth factor-β1 (TGF-β1). Besides cardiovascular diseases and infections, several studies show that Vitamin D status has been considered as a non-traditional risk factor for the progression of CKD. Given the importance of vitamin D in the maintenance of essential physiological functions, we studied the events involved in the chronic kidney disease progression in rats submitted to ischemia/reperfusion injury under vitamin D deficiency (VDD).MethodsRats were randomized into four groups: Control; VDD; ischemia/reperfusion injury (IRI); and VDD+IRI. At the 62 day after sham or IRI surgery, we measured inulin clearance, biochemical variables and hemodynamic parameters. In kidney tissue, we performed immunoblotting to quantify expression of Klotho, TGF-β, and vitamin D receptor (VDR); gene expression to evaluate renin, angiotensinogen, and angiotensin-converting enzyme; and immunohistochemical staining for ED1 (macrophages), type IV collagen, fibronectin, vimentin, and α-smooth mucle actin. Histomorphometric studies were performed to evaluate fractional interstitial area.ResultsIRI animals presented renal hypertrophy, increased levels of mean blood pressure and plasma PTH. Furthermore, expansion of the interstitial area, increased infiltration of ED1 cells, increased expression of collagen IV, fibronectin, vimentin and α-actin, and reduced expression of Klotho protein were observed. VDD deficiency contributed to increased levels of plasma PTH as well as for important chronic tubulointerstitial changes (fibrosis, inflammatory infiltration, tubular dilation and atrophy), increased expression of TGF-β1 and decreased expression of VDR and Klotho protein observed in VDD+IRI animals.ConclusionThrough inflammatory pathways and involvement of TGF-β1 growth factor, VDD could be considered as an aggravating factor for tubulointerstitial damage and fibrosis progression following acute kidney injury induced by ischemia/reperfusion.
Highlights
In most countries, the incidence and prevalence of chronic kidney disease (CKD) have been increasing over the years mainly due to the aging population and the presence of diabetic nephropathy [1,2]
Concerning PTH data, we found significant higher levels of the respective hormone in Vitamin D Deficiency (VDD) (1,2506155) and VDD+Ischemia-Reperfusion Injury (IRI) (2,1876336), showing the negative feedback caused by vitamin D deficiency in these groups
Figure 3. [I] Expression of ED1 positive cells in the renal cortex of a control rat (A), a vitamin D deficient rat (B), in a rat submitted to ischemia/reperfusion injury (C), and in a vitamin D deficient rat submitted to ischemia/reperfusion injury (D). [II] Number of ED1 positive cells per field (0.087 mm2) evaluated 90 days after in Control (C), Vitamin D Deficiency (VDD), Ischemia-Reperfusion Injury (IRI), and Vitamin D Deficiency and Ischemia/Reperfusion Injury (VDD+IRI) groups
Summary
The incidence and prevalence of chronic kidney disease (CKD) have been increasing over the years mainly due to the aging population and the presence of diabetic nephropathy [1,2]. It has been shown that the mortality of patients with CKD is directly related to renal function associated with cardiovascular diseases and infections [6]. Such traditional risks explain only about half of mortality and various studies are being directed to non-traditional risk factors, such as vitamin D [6]. Besides cardiovascular diseases and infections, several studies show that Vitamin D status has been considered as a non-traditional risk factor for the progression of CKD. Given the importance of vitamin D in the maintenance of essential physiological functions, we studied the events involved in the chronic kidney disease progression in rats submitted to ischemia/reperfusion injury under vitamin D deficiency (VDD)
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