Vitamin D Deficiency Aggravates Chronic Kidney Disease Progression after Ischemic Acute Kidney Injury

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.

AKI Recovery Induced by Mesenchymal Stromal Cell-Derived Extracellular Vesicles Carrying MicroRNAs

“…GO enrichment analysis of these targets showed the over-representation of processes associated with the first stages of kidney damage and repair by stem cell administration, such as the cell adhesion molecules and MAPK signaling. 38 Interestingly, the Wnt signaling pathway, 39 ECM remodeling, 40 and the p53 pathway 41 were also present among the significant biologic processes identified (data not shown). These processes are usually associated with relevant stages in the transition from acute to chronic injury, such as vascular failure, interstitial fibrosis, and glomerulosclerosis development.…”

“…These processes are usually associated with relevant stages in the transition from acute to chronic injury, such as vascular failure, interstitial fibrosis, and glomerulosclerosis development. [38][39][40][41] By selecting in this set, only genes not reverted in EV-Dsh treatment with respect to AKI, 165 genes resulted as the possible miRNA targets. GO enrichment analysis of these genes showed that EV-Dshtreated mice overexpressed genes associated with processes related with the progression of kidney damage, such as the Wnt pathway, p53 signaling, ECM remodeling, and focal adhesion processes, like the untreated AKI.…”

1,25-(OH)2D3 and its analogue BXL-628 inhibit high glucose-induced activation of RhoA/ROCK pathway in HK-2 cells

“…Hyperglycemic conditions activate a number of important intracellular signaling pathways, including the TGF-β/SMAD, nuclear factor-κB and Rho/ROCK pathways (12,15,27,28), which serve crucial roles in the diabetic renal inflammation response, RAS activation, EMT and fibrosis (3,8,19,29). VitD and VDR have previously been demonstrated to have renal protective functions via their regulative role in pathways associated with the prevention of EMT and fibrosis (17,20,30,31). Peng et al (4) illustrated that high glucose was able to activate RhoA/Rho-kinase in MCs, leading to downstream activator protein-1 activation and fibronectin induction (4).…”

Use of Nonsteroidal Anti-Inflammatory Drugs and Risk of Chronic Kidney Disease in Subjects With Hypertension

“…Fifth, several studies have suggested that vitamin D deficiency or lack of calcium intake might be associated with CKD development and progression as well as cardiovascular events. [41][42][43][44] However, the information about vitamin supplements is not available in this study. Further investigation will be merited to evaluate the association between use of vitamin supplements and CKD development and progression (or with cardiovascular events).…”