Renoprotection by remote ischemic conditioning during elective coronary revascularization: A systematic review and meta-analysis of randomized controlled trials

BACKGROUND: Remote ischemic conditioning (RIC) has been recognized an emerging non-invasive approach for preventing acute kidney injury (AKI) in patients undergoing either elective coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI). On the other hand, accumulating evidence has indicated the involving role of pre-CABG contrast usage for coronary angiography in post-surgery AKI risk. Along with the shortening time delay of CABG after coronary angiography, and the prevalent hybrid coronary revascularization (HCR), the AKI prevention by RIC has faced challenges following coronary revascuralization. METHODS: Randomized controlled trials (RCTs) were searched from Pubmed, EMBase, and Cochrane library (until May 2016). The primary outcome was postoperative AKI. The second outcomes were included the requirement for renal replacement therapy (RRT), and in-hospital or 30-day mortality. RESULTS: Twenty eligible RCTs (CABG, 3357 patients; PCI, 1501 patients) were selected. RIC significantly halved the incidence of AKI following PCI when compared with controls [n=1501; odds ratio (OR)=0.51; 95% CI, 0.32 to 0.82; P=0.006; I(2)=29.6%]. However, RIC did not affect the incidence of AKI following CABG (n=1850; OR=0.94; 95% CI, 0.73 to 1.19; P=0.586; I(2)=12.4%). The requirement for RRT and in-hospital mortality was not affected by RIC in CABG (n=2049, OR=1.04, P=0.87; n=1920, OR=0.89, P=0.7; respectively). CONCLUSIONS: Our meta-analysis suggests that RIC for preventing AKI following CABG has faced with challenges in terms of AKI, the requirement for RRT, and mortality. However, RIC shows a renoprotective benefit for PCI. Hence, our findings may infer the preserved renal effects of RIC in CABG with preconditioning before the coronary angiography, or in HCR

EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI): Study protocol for a multicentre, observational trial

Introduction More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. Methods and analysis EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. Ethics and dissemination EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369

PSGL-1 engagement by E-selectin signals through Src kinase Fgr and ITAM adapters DAP12 and FcRγ to induce slow leukocyte rolling

E-selectin binding to P-selectin glycoprotein ligand-1 (PSGL-1) can activate the β2 integrin lymphocyte function-associated antigen-1 by signaling through spleen tyrosine kinase (Syk). This signaling is independent of Gαi-protein–coupled receptors, results in slow rolling, and promotes neutrophil recruitment to sites of inflammation. However, the signaling pathways linking E-selectin engagement of PSGL-1 to Syk activation are unknown. To test the role of Src family kinases and immunoreceptor tyrosine-based activating motif (ITAM)–containing adaptor proteins, we used different gene-deficient mice in flow chamber, intravital microscopy, and peritonitis studies. E-selectin–mediated phosphorylation of Syk and slow rolling was abolished in neutrophils from fgr−/− or hck−/− lyn−/− fgr−/− mice. Neutrophils from Tyrobp−/− Fcrg−/− mice lacking both DAP12 and FcRγ were incapable of sustaining slow neutrophil rolling on E-selectin and intercellular adhesion molecule-1 and were unable to phosphorylate Syk and p38 MAPK. This defect was confirmed in vivo by using mixed chimeric mice. Gαi-independent neutrophil recruitment into the inflamed peritoneal cavity was sharply suppressed in Tyrobp−/− Fcrg−/− mice. Our data demonstrate that an ITAM-dependent pathway involving the Src-family kinase Fgr and the ITAM-containing adaptor proteins DAP12 and FcRγ is involved in the initial signaling events downstream of PSGL-1 that are required to initiate neutrophil slow rolling

Early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury (The ELAIN-Trial): Study protocol for a randomized controlled trial

Background: Acute kidney injury remains a common complication in critically ill patients and despite multiple trials and observational studies, the optimal timing for initiation of renal replacement therapy is still unclear. The early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury (ELAIN) study is a randomized, single-center, prospective, two-arm, parallel group trial to reduce mortality in patients with severe acute kidney injury. We describe the study design and discuss aspects of the need for a trial in this patient cohort. Methods/design: Our plan is to randomize critically ill patients with acute kidney injury to 'early' or 'late' initiation of renal replacement therapy according to stage 2 and 3 of the KDIGO classification using a specific trial protocol. We plan to guide data collection and analysis using pre-existing definitions and testing. The primary endpoint is overall survival in a 90-day follow-up period. Secondary endpoints include 28-day, 60-day, 90-day and 1-year all-cause mortality, recovery of renal function, ICU and hospital length-of-stay. The primary analysis will be an intention-to-treat analysis; secondary analyses include treated analyses. We will also specify rules for handling data and determining outcome. Discussion: Several challenges for study design and execution can be seen in our trial, and it should generate results that will inform and influence the practice of renal replacement therapy in critically ill patients with acute kidney injury. Trial registration: German Clinical Trials Register: DRKS00004367 (www.germanctr.de); 28 May 2013

The effects of citrate dialysate in hemodialysis on polymorphonuclear elastase interaction with tissue factor and its inhibitor

Background: This study aimed to investigate whether hemodialysis (HD) affects tissue factor (TF), tissue factor pathway inhibitor (TFPI), and polymorphonuclear elastase (PMNE) in endstage renal disease (ESRD) patients when eliminating the effects of heparin. Also, to explore the interaction of TF, TFPI, and PMNE throughout a single HD session. Methods: We enrolled 57 ESRD patients who had undergone hemodialysis for >3 months as an experimental group. Plasma levels of TF, TFPI and PMNE were measured by ELISA in 24 ERSD patients on intermittent HD using low-molecular-weight heparin (LMWH) as anticoagulation (LMWH group) and 33 ESRD patients using citrate as anticoagulation (citrate group) at the start and at 1, 2 and 5 h of the HD session. Meanwhile,28 ESRD patients not on dialysis were enrolled as a control group and fasting venous blood samples were taken in the morning. Results: Compared with the control group, the plasma TFPI levels of the LMWH group and the citrate group were significantly higher (P=0.000, P=0.002, respectively) under baseline conditions as well as the plasma PMNE levels (P=0.001, P=0.02, respectively), whereas TF showed no difference (P=0.186). During HD with citrate, plasma TFPI decreased slightly (P=0.012) and PMNE increased significantly (P=0.008) at 1 h. The plasma TFPI levels of the citrate group correlate with PMNE at 2 and 5 h (P=0.001, P=0.008, respectively). Conclusions: ESRD patients on HD have significantly higher TFPI and PMNE levels compared to patients not on HD under baseline conditions, while TF levels were similar between the three groups. TFPI and PMNE are differently regulated, but the plasma levels correlated during HD in the citrate group. It might be possible that PMNE plays a role in anticoagulative activity through TFPI

Report of the first AKI Round Table meeting: an initiative of the ESICM AKI Section.

Critical Care Nephrology is an emerging sub-specialty of Critical Care. Despite increasing awareness about the serious impact of acute kidney injury (AKI) and renal replacement therapy (RRT), important knowledge gaps persist. This report represents a summary of a 1-day meeting of the AKI section of the European Society of Intensive Care Medicine (ESICM) identifying priorities for future AKI research. International Members of the AKI section of the ESICM were selected and allocated to one of three subgroups: "AKI diagnosis and evaluation", "Medical management of AKI" and "Renal Replacement Therapy for AKI." Using a modified Delphi methodology, each group identified knowledge gaps and developed potential proposals for future collaborative research. The following key research projects were developed: Systematic reviews: (a) epidemiology of AKI with stratification by patient cohorts and diagnostic criteria; (b) role of higher blood pressure targets in patients with hypertension admitted to the Intensive Care Unit, and (c) specific clearance characteristics of different modalities of continuous renal replacement therapy (CRRT). Observational studies: (a) epidemiology of critically ill patients according to AKI duration, and (b) current clinical practice of CRRT. Intervention studies:( a) Comparison of different blood pressure targets in critically ill patients with hypertension, and (b) comparison of clearance of solutes with various molecular weights between different CRRT modalities. Consensus was reached on a future research agenda for the AKI section of the ESICM