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Xu X.,Sun Yat Sen University | Kriegel A.J.,Medical College of Wisconsin | Jiao X.,Sun Yat Sen University | Liu H.,Sun Yat Sen University | And 7 more authors.
Physiological Genomics

MicroRNAs (miRNAs or miRs) are endogenous, small RNA molecules that suppress expression of targeted mRNA. miR-21 in ischemia/reperfusion injury: a double-edged sword?. Physiol Genomics 46: 789-797, 2014. First published August 26, 2014; doi:10.1152/physiolgenomics.00020.2014.— MicroRNAs (miRNAs or miRs) are endogenous, small RNA molecules that suppress expression of targeted mRNA. miR-21, one of the most extensively studied miRNAs, is importantly involved in divergent pathophysiological processes relating to ischemia/reperfusion (I/R) injury, such as inflammation and angiogenesis. The role of miR-21 in renal I/R is complex, with both protective and pathological pathways being regulated by miR-21. Preconditioning-induced upregulation of miR-21 contributes to the protection against subsequent renal I/R injury through the targeting of genes such as the proapoptotic gene programmed cell death 4 and interactions between miR-21 and hypoxia-inducible factor. Conversely, long-term elevation of miR-21 may be detrimental to the organ by promoting the development of renal interstitial fibrosis following I/R injury. miR-21 is importantly involved in several pathophysiological processes related to I/R injury including inflammation and angiogenesis as well as the biology of stem cells that could be used to treat I/R injury; however, the effect of miR-21 on these processes in renal I/R injury remains to be studied. © 2014 the American Physiological Society. Source

Jia P.,Fudan University | Jia P.,Kidney and Dialysis Institute of Shanghai | Jia P.,Kidney and Blood Purification Laboratory of Shanghai | Jin W.,Fudan University | And 9 more authors.
Medicine (United States)

Endothelial dysfunction and chronic inflammatory process are prevalent in patients with end-stage renal disease (ESRD) on maintenance hemodialysis (HD). The aim of this study was to evaluate the acute and short-term effects of online hemodiafiltration (OL-HDF) versus conventional HD on endothelial function and inflammation. A prospective, randomized, crossover trial. Twenty stable ESRD patients undergoing chronic HD treatments were randomly assigned with a 1:1 ratio to conventional HD and to OLHDF both for 2 weeks (either HD followed by OL-HDF or OL-HDF followed by HD). Markers of endothelial dysfunction such as flowmediated dilatation (FMD) of the brachial artery, soluble endothelial protein C receptor (sEPCR), and soluble thrombomodulin (sTM) were measured at baseline, after the first dialysis session and after 2 weeks. Meanwhile, serum interleukin 6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP) levels were measured as well. Both a single OL-HDF session and 2-week OL-HDF significantly improved brachial FMD% (18.76.9% at baseline; 21.5±5.4% after the first dialysis; 21.5±5.7% after 2 weeks; P<0.05 vs baseline), decreased the levels of sEPCR (from 394.4 [297.9-457.0] ng/ml at baseline to 234.7 [174.1-345.5] ng/ml after the first dialysis, and to 191.5 [138.2-255.0] ng/ml after 2 weeks; P<0.01 vs baseline) and sTM. In contrast, HD did not change FMD%, even increased the levels of sEPCR and sTM. A reduction in IL-6 level was observed in OL-HDF patients after 2-week dialysis, while IL-6 did not change in HD patients. There was no significant difference in change of hs-CRP level between the OL-HDF and HD treatments. OL-HDF has both acute and short-term beneficial effects on endothelial dysfunction compared to conventional HD. © 2016 Wolters Kluwer Health, Inc. All rights reserved. Source

Jia P.,Fudan University | Jia P.,Kidney and Dialysis Institute of Shanghai | Jia P.,Kidney and Blood Purification Laboratory of Shanghai | Teng J.,Fudan University | And 8 more authors.
Critical Care Medicine

Objectives: Septic acute kidney injury is one of the most common and life-threatening complications in critically ill patients, and there is no approved effective treatment. We have shown xenon provides renoprotection against ischemia-reperfusion injury and nephrotoxicity in rodents via inhibiting apoptosis. Here, we studied the effects of xenon preconditioning on septic acute kidney injury and its mechanism. Design: Experimental animal investigation. Setting: University research laboratory. Subjects: Experiments were performed with male C57BL/6 mice, 10 weeks of age, weighing 20-25 g. Interventions: We induced septic acute kidney injury by a single intraperitoneal injection of Escherichia coli lipopolysaccharide at a dose of 20 mg/kg. Mice were exposed for 2 hours to either 70% xenon or 70% nitrogen, 24 hours before the onset of septic acute kidney injury. In vivo knockdown of miR-21 was performed using locked nucleic acid-modified anti-miR, the role of miR-21 in renal protection conferred by the xenon preconditioning was examined, and miR-21 signaling pathways were analyzed. Measurements and Main Results: Xenon preconditioning provided morphologic and functional renoprotection, characterized by attenuation of renal tubular damage, apoptosis, and a reduction in inflammation. Furthermore, xenon treatment significantly upregulated the expression of miR-21 in kidney, suppressed proinflammatory factor programmed cell death protein 4 expression and nuclear factor-κB activity, and increased interleukin-10 production. Meanwhile, xenon preconditioning also suppressed the expression of proapoptotic protein phosphatase and tensin homolog deleted on chromosome 10, activating protein kinase B signaling pathway, subsequently increasing the expression of antiapoptotic B-cell lymphoma-2, and inhibiting caspase-3 activity. Knockdown of miR-21 upregulated its target effectors programmed cell death protein 4 and phosphatase and tensin homolog deleted on chromosome 10 expression, resulted in an increase in apoptosis, and exacerbated lipopolysaccharide-induced acute kidney injury. Conclusion: Our findings demonstrated that xenon preconditioning protected against lipopolysaccharide-induced acute kidney injury via activation of miR-21 target signaling pathways. © 2015 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. Source

Xu J.-R.,Fudan University | Xu J.-R.,Kidney and Dialysis Institute of Shanghai | Zhu J.-M.,Fudan University | Zhu J.-M.,Kidney and Dialysis Institute of Shanghai | And 13 more authors.
Medicine (United States)

The aim of the study was to evaluate risk factors for long-term mortality and progressive chronic kidney disease (CKD) after cardiac surgery in patients with normal preoperative renal function and postoperative acute kidney injury (AKI). From April 2009 to December 2012, we prospectively enrolled 3245 cardiac surgery patients of our hospital. The primary endpoints included survival rates and the secondary endpoint was the incidence of progressive chronic kidney disease (CKD) in a follow-up period of 2 years. Acute kidney injury was staged by KDIGO classification. Progressive CKD was defined as GFR ≤ 30mL/min/1.73m 2 or end-stage renal disease (ESRD) (starting renal replacement therapy or renal transplantation). The AKI incidence was 39.9% (n=1295). The 1 and 2 year overall survival (OS) rates of AKI patients were significantly lower than that for non-AKI patients (85.9% and 82.3% vs 98.1% and 93.7%, P<0.001), even after complete recovery of renal function during 2 years after intervention (P<0.001). The 2-year overall survival (OS) rates of patients with AKI stage 1, 2, and 3 were 89.9%, 78.6%, and 61.4% (P<0.001), respectively. Multivariate Cox regression analysis of factors for 2-year survival rates revealed that besides age (P<0.001), chronic cardiac failure (P<0.001), diabetes (P<0.001), cardiopulmonary bypass time (P<0.01), and length of intensive care unit (ICU) stay (P=0.004), AKI was a significant risk factor for reducing 2-year survival rates even after complete recovery of renal function (P<0.001). The accumulated progressive CKD prevalence was significantly higher in AKI than in non-AKI patients (6.8% vs 0.2%, P<0.001) in the 2 years after surgery. Even with complete recovery of renal function at discharge, AKI was still a risk factor for accumulated progressive CKD (RR 1.92, 95% CI 1.37-2.69). The 2-year mortality and progressive CKD incidence even after complete recovery of renal function were significantly increased in cardiac surgery patients with postoperative AKI. © 2015 Wolters Kluwer Health, Inc. Source

Teng J.,Fudan University | Teng J.,Kidney and Dialysis Institute of Shanghai | Teng J.,Kidney and Blood Purification Laboratory of Shanghai | Tian J.,Fudan University | And 18 more authors.
Hemodialysis International

The aim of this study is to investigate the effects of endogenous vasoactive substances on the occurrence of intradialytic hypertension (IDH) in patients during maintenance hemodialysis. Thirty-four maintenance hemodialysis patients were enrolled in this trial, and 17 of them were diagnosed with IDH (defined as an increase in blood pressure of at least 10mmHg during or immediately after a hemodialysis session), while 17 age-matched and sex-matched controls without IDH were selected for a retrospective comparison. We collected patients' blood samples before and after a dialysis session and measured the plasma levels of N-terminal fragment brain natriuretic peptide, renin, angiotensin-II, aldosterone (ALD), angiotensin-converting enzyme (ACE), endothelin-1 (ET-1), nitric oxide (NO), norepinephrine (NOR), and adrenomedullin. The post-dialysis serum ET-1 concentrations were significantly higher (4.09±2.06 vs. 2.75±1.34pg/mL, P<0.05), while the post-dialysis ratio of NO to ET-1 was lower (17.79±5.65 vs. 24.78±12.04, P<0.05) in IDH patients compared with the control group. Post-dialysis ALD and NOR values were significantly lower (P<0.01) and ACE levels were significantly higher (P<0.01) than the pre-dialysis concentrations only in the control and not in the IDH group. All other measured factors did not differ significantly between the groups and between pre-dialysis and post-dialysis determinations. Compared with blood angiotensin-II, ALD, ACE, NOR, adrenomedullin, N-terminal fragment brain natriuretic peptide, and NO status, inappropriately elevated ET-1 plasma concentrations may play a predominant role in the pathogenesis of IDH. © 2014 International Society for Hemodialysis. Source

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