Background.This study investigated whether quercetin could alleviate vascular calcification in experimental chronic renal failure rats induced by adenine.Methods.32 adult male Wistar rats were randomly divided into 4 groups fed normal diet, normal diet with quercetin supplementation (25 mg/kg·BW/d), 0.75% adenine diet, or adenine diet with quercetin supplementation. All rats were sacrificed after 6 weeks of intervention. Serum renal functions biomarkers and oxidative stress biomarkers were measured and status of vascular calcification in aorta was assessed. Furthermore, the induced nitric oxide synthase (iNOS)/p38 mitogen activated protein kinase (p38MAPK) pathway was determined to explore the potential mechanism.Results.Adenine successfully induced renal failure and vascular calcification in rat model. Quercetin supplementation reversed unfavorable changes of phosphorous, uric acid (UA) and creatinine levels, malonaldehyde (MDA) content, and superoxide dismutase (SOD) activity in serum and the increases of calcium and alkaline phosphatase (ALP) activity in the aorta (P<0.05) and attenuated calcification and calcium accumulation in the medial layer of vasculature in histopathology. Western blot analysis showed that iNOS/p38MAPK pathway was normalized by the quercetin supplementation.Conclusions.Quercetin exerted a protective effect on vascular calcification in adenine-induced chronic renal failure rats, possibly through the modulation of oxidative stress and iNOs/p38MAPK pathway.

Background and Aim: The study aimed to prospectively evaluate the effects of lowering the dialysate calcium concentration (DCa) to 1.25 mmol/l on Chinese patients undergoing maintenance hemodialysis (MHD), which are largely unknown to date. Methods: A singer-center, prospective, randomized trial was conducted for 2 years. The DCa in one group was decreased from 1.5 to 1.25 mmol/l but there was no change in the other group. The clinical outcomes, biochemical parameters, medicine treatments and markers of vascular change were compared among the 2 groups at different time intervals. Results: At baseline, the groups were similar with respect to serum levels of calcium, phosphorus, intact parathyroid hormone and fibroblast growth factor-23 as well as carotid intima-media thickness (cIMT) and carotid-femoral pulse wave velocity (cf-PWV). It was found that the serum phosphorus concentration in the lower DCa group had decreased markedly at 2-year follow-up (0-month: 7.13 ± 1.56 mg/dl; 24-month: 5.92 ± 1.73 mg/dl; p = 0.005). Serum calcium (p = 0.018), cIMT (p = 0.029) and cf-PWV (p = 0.024) in DCa 1.25 group were significantly lower than those in 1.5 group at the 24-month visit. Kaplan-Meier curve revealed that patients in DCa 1.25 group had a better rate of survival. In the multivariate Cox regression analysis, cIMT (HR 1.010; 95% CI 1.002-1.217; p = 0.015) and cf-PWV (HR 1.265; 95% CI 1.022-1.567; p = 0.031) were potential risk factors for mortality in those patients. Importantly, we showed that the average change in these 2 risk variables were both associated with the average change in levels of serum calcium and phosphorus. Conclusion: Our results indicate that lowering DCa to 1.25 mmol/l may be suitable for the MHD patients in our unit.

The present study aimed to identify the characteristics and cross‑talk between transforming growth factor β1 (TGF‑β1) and calcium ions in nephrolithiasis patients with idiopathic hypercalciuria (IH) in order to elucidate the potential mechanisms underlying changes in cell phenotype induced by bone‑associated factors and their influence on renal nephrolithiasis formation. Blood samples from a total of 29 nephrolithiasis patients with IH, 29 renal stone patients without IH and 29 healthy age‑matched normal controls were subjected to quantification of peripheral serum TGF‑β1, osteopontin (OPN) and bone morphogenetic protein 2 (BMP2) using ELISA. This was followed by detection of BMP2, OPN and 1,25‑dihydroxyvitamin D3 receptor (VDR) mRNA and protein levels in primary renal epithelial cells (PRECs) of IH and HK‑2 human proximal tubular cell lines (control) using reverse transcription quantitative polymerase chain reaction (RT‑qPCR) and western blot analyses. The mRNA expression levels of BMP2, OPN and VDR in PRECs and HK‑2 were evaluated following stimulation with various concentrations of TGF‑β1 (0.5, 2.0 and 5.0 ng/ml), Ca2+ (0.5, 1.5 and 2.5 mM) or TGF‑β1 and Ca2+ combined using RT‑qPCR, respectively. TGF‑β1, BMP2 and OPN expression levels in patients with IH were all significantly higher than those in the control group. The mRNA and protein expression levels of BMP2 and VDR were significantly higher in PRECs than those in HK‑2 cells. Following incubation with TGF‑β1 and/or Ca2+, the mRNA expression levels of BMP2, OPN and VDR in PRECs increased in a dose‑dependent manner; however, no significant differences were observed in HK‑2 cells with increasing TGF‑β1 dosage. Co‑incubation with TGF‑β1 and Ca2+ in PRECs and HK‑2 cell lines resulted in similar effects and the expression of BMP2, OPN and VDR mRNA increased in a time‑dependent manner. In conclusion, the results of the present study demonstrated that TGF‑β1 regulated the expression of BMP2, OPN and VDR in PRECs, but not in HK‑2 cells. Co‑incubation with TGF‑β1 and Ca2+ significantly increased the expression levels of bone‑associated factors in PRECs and HK‑2 cells, which suggested that this process may be partially responsible for the pathogenesis of calcium stone development, and also associated with bone formation and the TGF‑β1‑induced epithelial to mesenchymal transition.