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BACKGROUND: Prospective, single-center trials have shown that the implementation of the Kidney Disease: Improving Global Outcomes (KDIGO) recommendations in high-risk patients significantly reduced the development of acute kidney injury (AKI) after surgery. We sought to evaluate the feasibility of implementing a bundle of supportive measures based on the KDIGO guideline in high-risk patients undergoing cardiac surgery in a multicenter setting in preparation for a large definitive trial. METHODS: In this multicenter, multinational, randomized controlled trial, we examined the adherence to the KDIGO bundle consisting of optimization of volume status and hemodynamics, functional hemodynamic monitoring, avoidance of nephrotoxic drugs, and prevention of hyperglycemia in high-risk patients identified by the urinary biomarkers tissue inhibitor of metalloproteinases-2 [TIMP-2] and insulin growth factor-binding protein 7 [IGFBP7] after cardiac surgery. The primary end point was the adherence to the bundle protocol and was evaluated by the percentage of compliant patients with a 95% confidence interval (CI) according to Clopper-Pearson. Secondary end points included the development and severity of AKI. RESULTS: In total, 278 patients were included in the final analysis. In the intervention group, 65.4% of patients received the complete bundle as compared to 4.2% in the control group (absolute risk reduction [ARR] 61.2 [95% CI, 52.6-69.9]; P < .001). AKI rates were statistically not different in both groups (46.3% intervention versus 41.5% control group; ARR -4.8% [95% CI, -16.4 to 6.9]; P = .423). However, the occurrence of moderate and severe AKI was significantly lower in the intervention group as compared to the control group (14.0% vs 23.9%; ARR 10.0% [95% CI, 0.9-19.1]; P = .034). There were no significant effects on other specified secondary outcomes. CONCLUSIONS: Implementation of a KDIGO-derived treatment bundle is feasible in a multinational setting. Furthermore, moderate to severe AKI was significantly reduced in the intervention group.

Rationale: The renin–angiotensin–aldosterone system is a major pathway in regulating blood pressure, glomerular filtration, and fluid homeostasis. During inflammatory diseases, generation of angiot...

We have previously shown that remote ischemic preconditioning reduces acute kidney injury (acute kidney injury) in high-risk patients undergoing cardiopulmonary bypass and that the protective effect is confined to patients who exhibit an increased urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 in response to remote ischemic preconditioning. The purpose of this study was to determine the optimal intensity of remote ischemic preconditioning to induce required [tissue inhibitor of metalloproteinases-2]*[insulin-like growth factor-binding protein 7] changes and further explore mechanisms of remote ischemic preconditioning.Observational and randomized controlled, double-blind clinical trial.University Hospital of Muenster, Germany.High-risk patients undergoing cardiac surgery as defined by the Cleveland Clinic Foundation Score.In the interventional part, patients were randomized to receive either one of four different remote ischemic preconditioning doses (3 × 5 min, 3 × 7 min, 3 × 10 min remote ischemic preconditioning, or 3 × 5 min remote ischemic preconditioning + 2 × 10 min remote ischemic preconditioning in nonresponders) or sham-remote ischemic preconditioning (control).The primary endpoint of the interventional part was change in urinary [tissue inhibitor of metalloproteinases-2]*[insulin-like growth factor-binding protein 7] between pre- and postintervention. To examine secondary objectives including acute kidney injury incidence, we included an observational cohort. A total of 180 patients were included in the trial (n = 80 observational and n = 100 randomized controlled part [20 patients/group]). The mean age was 69.3 years (10.5 yr), 119 were men (66.1%). Absolute changes in [tissue inhibitor of metalloproteinases-2]*[insulin-like growth factor-binding protein 7] were significantly higher in all remote ischemic preconditioning groups when compared with controls (p0.01). Although we did not observe a dose-response relationship on absolute changes in [tissue inhibitor of metalloproteinases-2]*[insulin-like growth factor-binding protein 7] across the four different remote ischemic preconditioning groups, in the 15 patients failing to respond to the lowest dose, nine (60%) responded to a subsequent treatment at a higher intensity. Compared with controls, fewer patients receiving remote ischemic preconditioning developed acute kidney injury within 72 hours after surgery as defined by both Kidney Disease: Improving Global Outcomes criteria (30/80 [37.5%] vs 61/100 [61.0%]; p = 0.003).All doses of remote ischemic preconditioning significantly increased [tissue inhibitor of metalloproteinases-2]*[insulin-like growth factor-binding protein 7] and significantly decreased acute kidney injury compared with controls. High-dose remote ischemic preconditioning could stimulate [tissue inhibitor of metalloproteinases-2]*[insulin-like growth factor-binding protein 7] increases in patients refractory to low-dose remote ischemic preconditioning.

BACKGROUND: The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend a bundle of different measures for patients at increased risk of acute kidney injury (AKI). Prospective, single-center, randomized controlled trials (RCTs) have shown that management in accordance with the KDIGO recommendations was associated with a significant reduction in the incidence of postoperative AKI in high-risk patients. However, compliance with the KDIGO bundle in routine clinical practice is unknown. METHODS: This observational prevalence study was performed in conjunction with a prospective RCT investigating the role of the KDIGO bundle in high-risk patients undergoing cardiac surgery. A 2-day observational prevalence study was performed in all participating centers before the RCT to explore routine clinical practice. The participating hospitals provided the following data: demographics and surgical characteristics, AKI rates, and compliance rates with the individual components of the bundle. RESULTS: Ninety-five patients were enrolled in 12 participating hospitals. The incidence of AKI within 72 hours after cardiac surgery was 24.2%. In 5.3% of all patients, clinical management was fully compliant with all 6 components of the bundle. Nephrotoxic drugs were discontinued in 52.6% of patients, volume optimization was performed in 70.5%, 52.6% of the patients underwent functional hemodynamic monitoring, close monitoring of serum creatinine and urine output was undertaken in 24.2% of patients, hyperglycemia was avoided in 41.1% of patients, and no patient received radiocontrast agents. The patients received on average 3.4 (standard deviation [SD] +/- 1.1) of 6 supportive measures as recommended by the KDIGO guidelines. There was no significant difference in the number of applied measures between AKI and non-AKI patients (3.2 [SD +/- 1.1] vs 3.5 [SD +/- 1.1]; P = .347). CONCLUSIONS: In patients after cardiac surgery, compliance with the KDIGO recommendations was low in routine clinical practice.

Background: Hyperreninemia after cardiac surgery is associated with cardiovascular instability. Angiotensin II (AT-II) could potentially attenuate hyperreninemia while maintaining target blood pressure. This study assesses the association between AT-II usage and renin levels in cardiac surgery patients with postoperative hyperreninemia and vasoplegia. Methods: Between September 2020 and March 2021, we retrospectively identified 40 cardiac surgery patients with high Δ-renin levels (4 hours after cardiopulmonary bypass [CPB] minus preoperative levels) (defined as higher than 3.7 µU/mL) and vasopressor use who received a vasopressor therapy with either AT-II or continued norepinephrine alone. The primary outcome was the renin plasma level at 12 hours after surgery, adjusted by the renin plasma level at 4 hours after surgery. Results: Overall, the median renin plasma concentration increased from a baseline with median of 44.3 µU/mL (Q1-Q3, 14.6-155.5) to 188.6 µU/mL (Q1-Q3, 29.8-379.0) 4 hours after CPB. High Δ-renin (difference between postoperation and preoperation) patients (higher than 3.7 µU/mL) were then treated with norepinephrine alone (median dose of 3.25 mg [Q1-Q3, 1.00-4.75]) or with additional AT-II (norepinephrine dose: 1.33 mg [Q1-Q3, 0.78-2.04]; AT-II dose: 0.34 mg [Q1-Q3, 0.29-0.78]). At 12 hours after surgery, AT-II patients had lower renin levels than standard of care patients (71.7 µU/mL [Q1-Q3, 21.9-211.4] vs 130.6 µU/mL [Q1-Q3, 62.9-317.0]; P = .034 adjusting for the renin plasma level at 4 hours after surgery). Conclusions: In cardiac surgery patients with hypotonia and postoperative high Δ-renin levels, AT-II was associated with reduced renin plasma levels for at 12 hours and significantly decreased norepinephrine use, while norepinephrine alone was associated with increased renin levels. Further studies of AT-II in cardiac surgery appear justified.

Objective Outcomes after acute kidney injury are affected by both the severity and the duration of the insult. Patients with persistent acute kidney injury have higher major adverse kidney events, including 90-day mortality, renal replacement therapy, and persistent kidney dysfunction. Methods to identify these patients are urgently needed to improve outcomes. The purpose of this study was to evaluate whether biomarkers, including C-C motif chemokine ligand 14, were able to predict persistent acute kidney injury and major adverse kidney events after cardiac surgery. Methods This study was a single-center, prospective, observational study. Patients who developed moderate or severe acute kidney injury (Kidney Disease Improving Global Outcomes 2 or 3) within 72 hours after cardiac surgery were enrolled with a primary end point of persistent severe acute kidney injury (Kidney Disease Improving Global Outcomes 3) lasting 72 hours or more. Results A total of 100 patients were available for the primary analysis, and 37 met the primary end point. C-C motif chemokine ligand 14 was the most predictive biomarker for the primary end point with an area under the curve of 0.930 (95% confidence interval, 0.881-0.979). The area under the curve of C-C motif chemokine ligand 14 was significantly higher than the area under the curve for the other biomarkers analyzed. C-C motif chemokine ligand 14 was significantly higher in end point positive patients at enrollment (4.47 ng/mL [2.35-11.5] vs 0.67 ng/mL [0.38-1.07]; P = .001). Sensitivity and specificity were 78% and 95% at a cutoff value of 2.21 ng/mL, respectively. C-C motif chemokine ligand 14 was also highly accurate for predicting renal replacement therapy within 7 days (area under the curve, 0.915; 95% confidence interval, 0.858-0.972; P Conclusions Elevated C-C motif chemokine ligand 14 levels predict persistent acute kidney injury in cardiac surgery patients with moderate or severe acute kidney injury. This new biomarker may help stratify patients destined to receive renal replacement therapy and identify patients who may benefit from novel therapeutic approaches to acute kidney injury.

Acute kidney injury is a common complication after cardiac surgery, with a high impact on morbidity and mortality. Vascular adhesion protein-1 is involved in inflammation, which, in turn, is part of the development of acute kidney injury after cardiac surgery.In this ancillary study to the RENal effects of Remote Ischemic Preconditioning in cardiac surgery trial, we investigated whether vascular adhesion protein-1 might be associated with the development of acute kidney injury in high-risk patients after cardiac surgery. In total, 114 patients were included in this data set. Acute kidney injury was defined by the Kidney Disease: Improving Global Outcomes criteria serum creatinine and/or urine output. Vascular adhesion protein-1 concentrations were measured at baseline (before surgery), 4 hours, and 12 hours after cardiopulmonary bypass.Vascular adhesion protein-1 levels at 12 hours were significantly higher in patients with acute kidney injury (no acute kidney injury, 271 ng/mL [Q1, Q3, 179, 364 ng/mL] versus acute kidney injury, 384 ng/mL [Q1, Q3, 311, 478 ng/mL]; P.001). Moreover, patients developing acute kidney injury had higher differences in vascular adhesion protein-1 levels between 12 hours and baseline (P.001) and between 12 and 4 hours (P.001) after cardiopulmonary bypass. At a cut point difference value of 99 ng/mL (95% CI, 63-133) between 12 hours and baseline, patients with differences99 ng/mL showed a higher occurrence rate of acute kidney injury (acute kidney injury, 78.6% versus no acute kidney injury, 31.5%; P.001). Receiver-operating characteristic curve analyses demonstrated best performance for vascular adhesion protein-1 levels at 12 hours for acute kidney injury within 72 hours after surgery, especially in the subgroup of patients with chronic kidney disease (area under the receiver-operating characteristic curve, 0.78; P.001).Vascular adhesion protein-1 is elevated in patients developing acute kidney injury assuming that vascular adhesion protein-1 plays a crucial role in the development of acute kidney injury in high-risk patients after cardiac surgery.

Opioid-free anaesthesia may enhance postoperative recovery by reducing opioid-related side effects such as nausea, hyperalgesia or tolerance. The objective was to investigate the impact of multimodal opioid-free general anaesthesia on postoperative nausea, vomiting, pain and morphine consumption compared to the traditional opioid-based approach.This study was conducted as a prospective parallel-group randomised controlled trial.Perioperative Care.152 adult women undergoing elective inpatient gynaecological laparoscopy.Patients were randomly assigned for opioid-free anaesthesia (Group OF) with dexmedetomidine, esketamine and sevoflurane or to have opioid-based anaesthesia (Group C) with sufentanil and sevoflurane.Primary outcome was the occurrence of nausea within 24 h after surgery. Patients were assessed for the incidence and severity of PONV, postoperative pain and morphine consumption and recovery characteristics.Patients in both groups had comparable clinical and surgical data. 69.7% of patients in the control group and 68.4% of patients in the opioid-free group met the primary endpoint (OR 1.06, 95% Confidence Interval (CI) (0.53; 2.12) p = 0.86). The incidence of clinically important PONV defined by the PONV impact scale was 8.1% (Group C) vs 10.5% (OF); p = 0.57). Antiemetic requirements, pain scores and morphine consumption were equivalent in both groups. Postoperative sedation was significantly increased in group OF (p 0.001), and the median length of stay at the post-anaesthesia care unit was 69.0 min (46.5-113.0) vs 50.0 (35.3-77.0) minutes in the control group (p 0.001).Opioid-free multimodal general anaesthesia is feasible but did not decrease the incidence of PONV, or reduce pain scores and morphine consumption compared to an opioid-containing anaesthetic regimen.

Sağır, Özlem (Balikesir Author), 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. ©

Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common complication after cardiac surgery and associated with a worse outcome. The pathogenesis of CSA-AKI is complex and multifactorial. Therapeutic options for severe CSA-AKI are limited to renal replacement therapy constituting a supportive measure. Therefore, risk identification, prevention, and early diagnosis are of utmost importance to improve patient outcomes. This review aims to provide an overview of the diagnosis, pathophysiologic mechanisms, and risk factors of CSA-AKI and delineates the strategies for AKI prevention available to improve patient outcomes after cardiac surgery.

IMPORTANCE: Although current guidelines suggest the use of regional citrate anticoagulation (which involves the addition of a citrate solution to the blood before the filter of the extracorporeal dialysis circuit) as first-line treatment for continuous kidney replacement therapy in critically ill patients, the evidence for this recommendation is based on few clinical trials and meta-analyses. OBJECTIVE: To determine the effect of regional citrate anticoagulation, compared with systemic heparin anticoagulation, on filter life span and mortality. DESIGN, SETTING, AND PARTICIPANTS: A parallel-group, randomized multicenter clinical trial in 26 centers across Germany was conducted between March 2016 and December 2018 (final date of follow-up, January 21, 2020). The trial was terminated early after 596 critically ill patients with severe acute kidney injury or clinical indications for initiation of kidney replacement therapy had been enrolled. INTERVENTIONS: Patients were randomized to receive either regional citrate anticoagulation (n = 300), which consisted of a target ionized calcium level of 1.0 to 1.40 mg/dL, or systemic heparin anticoagulation (n = 296), which consisted of a target activated partial thromboplastin time of 45 to 60 seconds, for continuous kidney replacement therapy. MAIN OUTCOMES AND MEASURES: Coprimary outcomes were filter life span and 90-day mortality. Secondary end points included bleeding complications and new infections. RESULTS: Among 638 patients randomized, 596 (93.4%) (mean age, 67.5 years; 183 [30.7%] women) completed the trial. In the regional citrate group vs systemic heparin group, median filter life span was 47 hours (interquartile range [IQR], 19-70 hours) vs 26 hours (IQR, 12-51 hours) (difference, 15 hours [95% CI, 11 to 20 hours]; P

IntroductionAcute kidney injury (AKI) is a frequent complication after cardiac surgery with adverse short-term and long-term outcomes. Although prevention of AKI (PrevAKI) is strongly recommended, the optimal strategy is uncertain. The Kidney Disease: Improving Global Outcomes (KDIGO) guideline recommended a bundle of supportive measures in high-risk patients. In a single-centre trial, we recently demonstrated that the strict implementation of the KDIGO bundle significantly reduced the occurrence of AKI after cardiac surgery. In this feasibility study, we aim to evaluate whether the study protocol can be implemented in a multicentre setting in preparation for a large multicentre trial.Methods and analysisWe plan to conduct a prospective, observational survey followed by a randomised controlled, multicentre, multinational clinical trial including 280 patients undergoing cardiac surgery with cardiopulmonary bypass. The purpose of the observational survey is to explore the adherence to the KDIGO recommendations in routine clinical practice. The second phase is a randomised controlled trial. The objective is to investigate whether the trial protocol is implementable in a large multicentre, multinational setting. The primary endpoint of the interventional part is the compliance rate with the protocol. Secondary endpoints include the occurrence of any AKI and moderate/severe AKI as defined by the KDIGO criteria within 72 hours after surgery, renal recovery at day 90, use of renal replacement therapy (RRT) and mortality at days 30, 60 and 90, the combined endpoint major adverse kidney events consisting of persistent renal dysfunction, RRT and mortality at day 90 and safety outcomes.Ethics and disseminationThe PrevAKI multicentre study has been approved by the leading Research Ethics Committee of the University of Münster and the respective Research Ethics Committee at each participating site. The results will be used to design a large, definitive trial.Trial registration numberNCT03244514.

Acute kidney injury (AKI) is a common complication in critically ill patients (1) affecting approximately 57.3% of all patients in the intensive care unit (ICU) and is associated with a high morbidity and mortality (2).

ZusammenfassungDie akute Nierenschädigung ist eine häufige Komplikation kritisch kranker Patienten auf Intensivstationen, die mit einer hohen Morbidität und Letalität einhergeht [1]. Sie ist ein unabhängiger Risikofaktor für ein verschlechtertes Outcome kritisch kranker Patienten [2]. Diese Übersichtsarbeit fasst die verfügbare Evidenz für die Indikation und den Einsatz von Nierenersatzverfahren bei akuter Nierenschädigung anhand aktueller Literatur zusammen.

Whether earlier initiation of RRT in critically ill patients with AKI can improve outcomes remains debated. We examined follow-up data from a large clinical trial to prospectively investigate the long-term outcomes associated with the timing of RRT initiation in such patients. We extended the follow-up of patients in the Early Versus Delayed Initiation of RRT in Critically Ill Patients with AKI (ELAIN) Trial from 90 days to 1 year after randomization for 230 (99.6%) patients. The primary outcome was a composite of major adverse kidney events (persistent renal dysfunction, dialysis dependence, and mortality) at 1 year. Secondary outcomes included inflammatory markers. Overall, 72 of 111 (64.9%) and 106 of 119 (89.1%) patients met the primary outcome in the early (stage 2 AKI) and delayed (stage 3 AKI) initiation groups, respectively (odds ratio [OR] with early initiation, 0.23; 95% confidence interval [95% CI], 0.11 to 0.45; P

Background In a multicenter, randomized trial, the authors enrolled patients at high-risk for acute kidney injury as identified by a Cleveland Clinic Foundation score of 6 or more. The authors enrolled 240 patients at four hospitals and randomized them to remote ischemic preconditioning or control. The authors found that remote ischemic preconditioning reduced acute kidney injury in high-risk patients undergoing cardiac surgery. The authors now report on the effects of remote ischemic preconditioning on 90-day outcomes. Methods In this follow-up study of the RenalRIP trial, the authors examined the effect of remote ischemic preconditioning on the composite endpoint major adverse kidney events consisting of mortality, need for renal replacement therapy, and persistent renal dysfunction at 90 days. Secondary outcomes were persistent renal dysfunction and dialysis dependence in patients with acute kidney injury. Results Remote ischemic preconditioning significantly reduced the occurrence of major adverse kidney events at 90 days (17 of 120 [14.2%]) versus control (30 of 120 [25.0%]; absolute risk reduction, 10.8%; 95% CI, 0.9 to 20.8%; P = 0.034). In those patients who developed acute kidney injury after cardiac surgery, 2 of 38 subjects in the remote ischemic preconditioning group (5.3%) and 13 of 56 subjects in the control group (23.2%) failed to recover renal function at 90 days (absolute risk reduction, 17.9%; 95% CI, 4.8 to 31.1%; P = 0.020). Acute kidney injury biomarkers were also increased in patients reaching the major adverse kidney event endpoint compared to patients who did not. Conclusions Remote ischemic preconditioning significantly reduced the 3-month incidence of a composite endpoint major adverse kidney events consisting of mortality, need for renal replacement therapy, and persistent renal dysfunction in high-risk patients undergoing cardiac surgery. Furthermore, remote ischemic preconditioning enhanced renal recovery in patients with acute kidney injury.

Cardiac surgery is associated with a high risk of postoperative acute kidney injury (AKI) and subsequent loss of kidney function. We explored the clinical utility of urinary dickkopf-3 (DKK3), a renal tubular stress marker, for preoperative identification of patients at risk for AKI and subsequent kidney function loss.This observational cohort study included patients who had cardiac surgery in a derivation cohort and those who had cardiac surgery in a validation cohort (RenalRIP trial). The study comprised consecutive patients who had elective cardiac surgery at the Saarland University Medical Centre (Homburg, Germany; derivation cohort) and those undergoing elective cardiac surgery (selected on the basis of a Cleveland Clinical Foundation score of 6 or higher) who were enrolled in the prospective RenalRIP multicentre trial (validation cohort) and who were randomly assigned to remote ischaemic preconditioning or a sham procedure. The association between the ratio of preoperative urinary concentrations of DKK3 to creatinine (DKK3:creatinine) and postoperative AKI, defined according to the Kidney Disease Improving Global Outcomes criteria, and subsequent kidney function loss, as determined by estimated glomerular filtration rate, was assessed.In the 733 patient in the derivation cohort, urinary concentrations of DKK3 to creatinine that were higher than 471 pg/mg were associated with significantly increased risk for AKI (odds ratio [OR] 1·65, 95% CI 1·10-2·47, p=0·015), independent of baseline kidney function. Compared with clinical and other laboratory measurements, urinary concentrations of DKK3:creatinine significantly improved AKI prediction (net reclassification improvement 0·32, 95% CI 0·23-0·42, p0·0001). High urinary DKK3:creatinine concentrations were independently associated with significantly lower kidney function at hospital discharge and after a median follow-up of 820 days (IQR 733-910). In the RenalRIP trial, preoperative urinary DKK3:creatinine concentrations higher than 471 pg/mg were associated with a significantly higher risk for AKI (OR 1·94, 95% CI 1·08-3·47, p=0·026), persistent renal dysfunction (OR 6·67, 1·67-26·61, p=0·0072), and dialysis dependency (OR 13·57, 1·50-122·77, p=0·020) after 90 days compared with DKK3:creatinine concentrations of 471 pg/mg or less. Urinary DKK3:creatinine concentrations higher than 471 pg/mg were associated with significantly higher risk for AKI (OR 2·79, 95% CI 1·45-5·37) and persistent renal dysfunction (OR 3·82, 1·32-11·05) only in patients having a sham procedure, but not remote ischaemic preconditioning (AKI OR 1·35, 0·76-2·39 and persistent renal dysfunction OR 1·05, 0·12-9·45).Preoperative urinary DKK3 is an independent predictor for postoperative AKI and for subsequent loss of kidney function. Urinary DKK3 might aid in the identification of patients in whom preventive treatment strategies are effective.No study funding.

While interleukin-1β (IL-1β) is a potent pro-inflammatory cytokine essential for host defense, high systemic levels cause life-threatening inflammatory syndromes. ATP, a stimulus of IL-1β maturation, is released from damaged cells along with β-nicotinamide adenine dinucleotide (β-NAD). Here, we tested the hypothesis that β-NAD controls ATP-signaling and, hence, IL-1β release. Lipopolysaccharide-primed monocytic U937 cells and primary human mononuclear leukocytes were stimulated with 2′(3′)-O-(4-benzoyl-benzoyl)ATP trieethylammonium salt (BzATP), a P2X7 receptor agonist, in the presence or absence of β-NAD. IL-1β was measured in cell culture supernatants. The roles of P2Y receptors, nicotinic acetylcholine receptors (nAChRs), and Ca2+-independent phospholipase A2 (iPLA2β, PLA2G6) were investigated using specific inhibitors and gene-silencing. Exogenous β-NAD signaled via P2Y receptors and dose-dependently (IC50 = 15 µM) suppressed the BzATP-induced IL-1β release. Signaling involved iPLA2β, release of a soluble mediator, and nAChR subunit α9. Patch-clamp experiments revealed that β-NAD inhibited BzATP-induced ion currents. In conclusion, we describe a novel triple membrane-passing signaling cascade triggered by extracellular β-NAD that suppresses ATP-induced release of IL-1β by monocytic cells. This cascade links activation of P2Y receptors to non-canonical metabotropic functions of nAChRs that inhibit P2X7 receptor function. The biomedical relevance of this mechanism might be the control of trauma-associated systemic inflammation.

Acute kidney injury (AKI) is a common complication in critically ill patients and is associated with a worse short- and long-term outcome. The KDIGO (Kidney Disease: Improving Global Outcomes) guidelines suggest to implement preventive strategies in high-risk patients. Definition and classification of acute kidney injury according to the KDIGO criteria are based on an increase in serum creatinine and/or a decrease in urinary output. Renal replacement therapy (RRT) is the only supportive measure in patients with severe AKI. The KDIGO guidelines recommend to initiate RRT immediately if an absolute indication exists. However, in the absence of absolute indication, there are no recommendations when to start RRT in AKI patients with a progressive decline of renal function. Continuous or intermittent techniques of renal replacement therapy may be used equally for treatment of acute kidney injury. In hemodynamically instable patients and patients with increased intracranial pressures continuous renal replacement therapy is recommended. Although weak evidence exists, regional citrate anticoagulation is suggested for patients receiving continuous renal replacement therapy and systemic heparin anticoagulation is suggested for patients receiving intermittent renal replacement therapy. The KDIGO guidelines recommend to deliver an effluent volume of 20 - 25 ml/kg/h for CRRT in AKI.Die akute Nierenschädigung ist eine häufige Komplikation kritisch kranker Patienten auf Intensivstationen, die mit einer hohen Morbidität und Letalität einhergeht [1]. Sie ist ein unabhängiger Risikofaktor für ein verschlechtertes Outcome kritisch kranker Patienten [2]. Diese Übersichtsarbeit fasst die verfügbare Evidenz für die Indikation und den Einsatz von Nierenersatzverfahren bei akuter Nierenschädigung anhand aktueller Literatur zusammen.

Acute kidney injury (AKI) is a common complication that occurs in critically ill patients and it is associated with a worse outcome. Since therapy options are limited, prevention and early detection are the essential cornerstones to improve patient outcomes. Therefore, using health information technology (HIT) to detect AKI early might be useful for clinicians. Patient data can be extracted real-time from electronic health records. Programmed electronic alert systems (e-alerts) can increase clinicians' awareness for AKI. Integrated into clinical decision support systems, implementation of HIT might improve clinical processes and patient outcomes. Several studies show the application of e-alerts in AKI detection and the implementation in processes of care. Monitoring nephrotoxic medication is one successful approach of implementing e-alerts in prevention of AKI. Information technology in AKI is in an early phase of development and further multicenter prospective studies are required to draw optimally on the maximum potential of this concept.

Acute kidney injury (AKI) is a common complication that occurs in critically ill patients and it is associated with a worse outcome. Since therapy options are limited, prevention and early detection are the essential cornerstones to improve patient outcomes. Therefore, using health information technology (HIT) to detect AKI early might be useful for clinicians. Patient data can be extracted real-time from electronic health records. Programmed electronic alert systems (e-alerts) can increase clinicians' awareness for AKI. Integrated into clinical decision support systems, implementation of HIT might improve clinical processes and patient outcomes. Several studies show the application of e-alerts in AKI detection and the implementation in processes of care. Monitoring nephrotoxic medication is one successful approach of implementing e-alerts in prevention of AKI. Information technology in AKI is in an early phase of development and further multicenter prospective studies are required to draw optimally on the maximum potential of this concept.

While interleukin-1β (IL-1β) is a potent pro-inflammatory cytokine essential for host defense, high systemic levels cause life-threatening inflammatory syndromes. ATP, a stimulus of IL-1β maturation, is released from damaged cells along with β-nicotinamide adenine dinucleotide (β-NAD). Here, we tested the hypothesis that β-NAD controls ATP-signaling and, hence, IL-1β release. Lipopolysaccharide-primed monocytic U937 cells and primary human mononuclear leukocytes were stimulated with 2′(3′)-O-(4-benzoyl-benzoyl)ATP trieethylammonium salt (BzATP), a P2X7 receptor agonist, in the presence or absence of β-NAD. IL-1β was measured in cell culture supernatants. The roles of P2Y receptors, nicotinic acetylcholine receptors (nAChRs), and Ca2+-independent phospholipase A2 (iPLA2β, PLA2G6) were investigated using specific inhibitors and gene-silencing. Exogenous β-NAD signaled via P2Y receptors and dose-dependently (IC50 = 15 µM) suppressed the BzATP-induced IL-1β release. Signaling involved iPLA2β, release of a soluble mediator, and nAChR subunit α9. Patch-clamp experiments revealed that β-NAD inhibited BzATP-induced ion currents. In conclusion, we describe a novel triple membrane-passing signaling cascade triggered by extracellular β-NAD that suppresses ATP-induced release of IL-1β by monocytic cells. This cascade links activation of P2Y receptors to non-canonical metabotropic functions of nAChRs that inhibit P2X7 receptor function. The biomedical relevance of this mechanism might be the control of trauma-associated systemic inflammation.

IL-1β is a potent proinflammatory cytokine of the innate immune system that is involved in host defense against infection. However, increased production of IL-1β plays a pathogenic role in various inflammatory diseases, such as rheumatoid arthritis, gout, sepsis, stroke, and transplant rejection. To prevent detrimental collateral damage, IL-1β release is tightly controlled and typically requires two consecutive danger signals. LPS from Gram-negative bacteria is a prototypical first signal inducing pro–IL-1β synthesis, whereas extracellular ATP is a typical second signal sensed by the ATP receptor P2X7 that triggers activation of the NLRP3-containing inflammasome, proteolytic cleavage of pro–IL-1β by caspase-1, and release of mature IL-1β. Mechanisms controlling IL-1β release, even in the presence of both danger signals, are needed to protect from collateral damage and are of therapeutic interest. In this article, we show that acetylcholine, choline, phosphocholine, phosphocholine-modified LPS from Haemophilus influenzae, and phosphocholine-modified protein efficiently inhibit ATP-mediated IL-1β release in human and rat monocytes via nicotinic acetylcholine receptors containing subunits α7, α9, and/or α10. Of note, we identify receptors for phosphocholine-modified macromolecules that are synthesized by microbes and eukaryotic parasites and are well-known modulators of the immune system. Our data suggest that an endogenous anti-inflammatory cholinergic control mechanism effectively controls ATP-mediated release of IL-1β and that the same mechanism is used by symbionts and misused by parasites to evade innate immune responses of the host.

Interleukin (IL)-1β is a potent pro-inflammatory cytokine of innate immunity involved in host defense. High systemic IL-1β levels, however, cause life-threatening inflammatory diseases, including systemic inflammatory response syndrome. In response to various danger signals, the pro-form of IL-1β is synthesized and stays in the cytoplasm unless a second signal, such as extracellular ATP, activates the inflammasome, which enables processing and release of mature IL-1β. As pulmonary surfactant is known for its anti-inflammatory properties, we hypothesize that surfactant inhibits ATP-induced release of IL-1β. Lipopolysaccharide-primed monocytic U937 cells were stimulated with an ATP analog in the presence of natural or synthetic surfactant composed of recombinant surfactant protein (rSP)-C, palmitoylphosphatidylglycerol, and dipalmitoylphosphatidylcholine (DPPC). Both surfactant preparations dose-dependently inhibited IL-1β release from U937 cells. DPPC was the active constituent of surfactant, whereas rSP-C and palmitoylphosphatidylglycerol were inactive. DPPC was also effective in primary mononuclear leukocytes isolated from human blood. Experiments with nicotinic antagonists, siRNA technology, and patch-clamp experiments suggested that stimulation of nicotinic acetylcholine receptors (nAChRs) containing subunit α9 results in a complete inhibition of the ion channel function of ATP receptor, P2X7. In conclusion, the surfactant constituent, DPPC, efficiently inhibits ATP-induced inflammasome activation and maturation of IL-1β in human monocytes by a mechanism involving nAChRs.