Acute kidney injury (AKI) is a complex disorder for which currently there is no accepted definition. Having a uniform standard for diagnosing and classifying AKI would enhance our ability to manage these patients. Future clinical and translational research in AKI will require collaborative networks of investigators drawn from various disciplines, dissemination of information via multidisciplinary joint conferences and publications, and improved translation of knowledge from pre-clinical research. We describe an initiative to develop uniform standards for defining and classifying AKI and to establish a forum for multidisciplinary interaction to improve care for patients with or at risk for AKI. Members representing key societies in critical care and nephrology along with additional experts in adult and pediatric AKI participated in a two day conference in Amsterdam, The Netherlands, in September 2005 and were assigned to one of three workgroups. Each group's discussions formed the basis for draft recommendations that were later refined and improved during discussion with the larger group. Dissenting opinions were also noted. The final draft recommendations were circulated to all participants and subsequently agreed upon as the consensus recommendations for this report. Participating societies endorsed the recommendations and agreed to help disseminate the results. The term AKI is proposed to represent the entire spectrum of acute renal failure. Diagnostic criteria for AKI are proposed based on acute alterations in serum creatinine or urine output. A staging system for AKI which reflects quantitative changes in serum creatinine and urine output has been developed. We describe the formation of a multidisciplinary collaborative network focused on AKI. We have proposed uniform standards for diagnosing and classifying AKI which will need to be validated in future studies. The Acute Kidney Injury Network offers a mechanism for proceeding with efforts to improve patient outcomes.

Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury

Rigorous evidence identification is essential for systematic reviews and meta-analyses (evidence syntheses) because the sample selection of relevant studies determines a review's outcome, validity, and explanatory power. Yet, the search systems allowing access to this evidence provide varying levels of precision, recall, and reproducibility and also demand different levels of effort. To date, it remains unclear which search systems are most appropriate for evidence synthesis and why. Advice on which search engines and bibliographic databases to choose for systematic searches is limited and lacking systematic, empirical performance assessments. This study investigates and compares the systematic search qualities of 28 widely used academic search systems, including Google Scholar, PubMed, and Web of Science. A novel, query-based method tests how well users are able to interact and retrieve records with each system. The study is the first to show the extent to which search systems can effectively and efficiently perform (Boolean) searches with regards to precision, recall, and reproducibility. We found substantial differences in the performance of search systems, meaning that their usability in systematic searches varies. Indeed, only half of the search systems analyzed and only a few Open Access databases can be recommended for evidence syntheses without adding substantial caveats. Particularly, our findings demonstrate why Google Scholar is inappropriate as principal search system. We call for database owners to recognize the requirements of evidence synthesis and for academic journals to reassess quality requirements for systematic reviews. Our findings aim to support researchers in conducting better searches for better evidence synthesis.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jrsm.1378

Which Academic Search Systems are Suitable for Systematic Reviews or Meta‐Analyses? Evaluating Retrieval Qualities of Google Scholar, PubMed and 26 other Resources

Acute kidney injury (AKI) is the leading cause of nephrology consultation and is associated with high mortality rates. The primary causes of AKI include ischemia, hypoxia or nephrotoxicity. An underlying feature is a rapid decline in GFR usually associated with decreases in renal blood flow. Inflammation represents an important additional component of AKI leading to the extension phase of injury, which may be associated with insensitivity to vasodilator therapy. It is suggested that targeting the extension phase represents an area potential of treatment with the greatest possible impact. The underlying basis of renal injury appears to be impaired energetics of the highly metabolically active nephron segments (i.e., proximal tubules and thick ascending limb) in the renal outer medulla, which can trigger conversion from transient hypoxia to intrinsic renal failure. Injury to kidney cells can be lethal or sublethal. Sublethal injury represents an important component in AKI, as it may profoundly influence GFR and renal blood flow. The nature of the recovery response is mediated by the degree to which sublethal cells can restore normal function and promote regeneration. The successful recovery from AKI depends on the degree to which these repair processes ensue and these may be compromised in elderly or CKD patients. Recent data suggest that AKI represents a potential link to CKD in surviving patients. Finally, earlier diagnosis of AKI represents an important area in treating patients with AKI that has spawned increased awareness of the potential that biomarkers of AKI may play in the future.

/pdf/pathophysiology-of-acute-kidney-injury-57ami3f8ia.pdf

Pathophysiology of Acute Kidney Injury

Sepsis, severe sepsis, and septic shock represent increasingly severe systemic inflammatory responses to infection. Sepsis is common in the aging population, and it disproportionately affects patients with cancer and underlying immunosuppression. In its most severe form, sepsis causes multiple organ dysfunction that can produce a state of chronic critical illness characterized by severe immune dysfunction and catabolism. Much has been learnt about the pathogenesis of sepsis at the molecular, cell, and intact organ level. Despite uncertainties in hemodynamic management and several treatments that have failed in clinical trials, investigational therapies increasingly target sepsis induced organ and immune dysfunction. Outcomes in sepsis have greatly improved overall, probably because of an enhanced focus on early diagnosis and fluid resuscitation, the rapid delivery of effective antibiotics, and other improvements in supportive care for critically ill patients. These improvements include lung protective ventilation, more judicious use of blood products, and strategies to reduce nosocomial infections.

https://www.bmj.com/content/bmj/353/bmj.i1585.full.pdf

Sepsis: pathophysiology and clinical management

OBJECTIVES: To develop evidence-based recommendations for clinicians caring for children (including infants, school-aged children, and adolescents) with septic shock and other sepsis-associated organ dysfunction. DESIGN: A panel of 49 international experts, representing 12 international organizations, as well as three methodologists and three public members was convened. Panel members assembled at key international meetings (for those panel members attending the conference), and a stand-alone meeting was held for all panel members in November 2018. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. Teleconferences and electronic-based discussion among the chairs, co-chairs, methodologists, and group heads, as well as within subgroups, served as an integral part of the guideline development process. METHODS: The panel consisted of six subgroups: recognition and management of infection, hemodynamics and resuscitation, ventilation, endocrine and metabolic therapies, adjunctive therapies, and research priorities. We conducted a systematic review for each Population, Intervention, Control, and Outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak, or as a best practice statement. In addition, "in our practice" statements were included when evidence was inconclusive to issue a recommendation, but the panel felt that some guidance based on practice patterns may be appropriate. RESULTS: The panel provided 77 statements on the management and resuscitation of children with septic shock and other sepsis-associated organ dysfunction. Overall, six were strong recommendations, 52 were weak recommendations, and nine were best-practice statements. For 13 questions, no recommendations could be made; but, for 10 of these, "in our practice" statements were provided. In addition, 49 research priorities were identified. CONCLUSIONS: A large cohort of international experts was able to achieve consensus regarding many recommendations for the best care of children with sepsis, acknowledging that most aspects of care had relatively low quality of evidence resulting in the frequent issuance of weak recommendations. Despite this challenge, these recommendations regarding the management of children with septic shock and other sepsis-associated organ dysfunction provide a foundation for consistent care to improve outcomes and inform future research.

Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-Associated Organ Dysfunction in Children

Background
Severe sepsis and septic shock are leading causes of death in the intensive care unit (ICU), despite advances in the treatment of patients with severe sepsis and septic shock, including early recognition, appropriate treatment with antibiotics and support of organs that may have been affected by the illness. High-volume haemofiltration (HVHF) is a blood purification technique that may improve outcomes in severe sepsis or septic shock. The technique of HVHF has evolved from renal replacement therapies used in the ICU to treat critically ill patients with acute kidney injury (AKI). This review was first published in 2013 and was updated in 2016.

Objectives
To investigate whether HVHF improves outcomes in critically ill adults admitted to the intensive care unit with severe sepsis or septic shock. The primary outcome of this systematic review is patient mortality; secondary outcomes include duration of stay, severity of organ dysfunction and adverse events.

Search methods
For this updated version, we extended searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Latin American Caribbean Health Sciences Literature (LILACS), Web of Science and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) to 31 December 2015. The original search was performed in 2011. We also searched trials registers.

Selection criteria
We included randomized controlled trials (RCTs) and quasi-randomized trials comparing HVHF or high-volume haemodiafiltration versus standard or usual dialysis therapy, as well as RCTs and quasi-randomized trials comparing HVHF or high-volume haemodiafiltration versus no similar dialysis therapy. These studies involved adults treated in critical care units.

Data collection and analysis
Three review authors independently extracted data and assessed trial quality. We sought additional information from trialists as required.

Main results
We included four randomized trials involving 200 participants. Owing to small numbers of studies and participants, it was not possible to combine data for all outcomes. Two trials reported 28-day mortality, and one trial reported hospital mortality; in the third trial, the number of deaths stated did not match the quoted mortality rates. The pooled risk ratio (95% confidence interval) for 28-day mortality associated with HVHF was 0.89 (0.60 to 1.32, two trials, 146 participants, low-quality evidence). One study (137 participants, low-quality evidence) reported length of stay in the ICU. Two trials (170 participants, low-quality evidence) reported organ dysfunction, but we could not pool results owing to reporting differences. Three studies (189 participants, low-quality evidence) reported on haemodynamic changes, but we could not pool results owing to reporting differences. Investigators reported no adverse events. Overall, the included studies had low risk of bias.

Authors' conclusions
Investigators reported no adverse effects of HVHF (low-quality evidence). The results of this meta-analysis show that very few studies have been conducted to investigate the use of HVHF in critically ill patients with severe sepsis or septic shock (four studies, 201 participants, low-quality evidence). Researchers should consider additional randomized controlled trials that are large and multi-centred and have clinically relevant outcome measures. The cost-effectiveness of HVHF should also be studied. .

/pdf/high-volume-haemofiltration-for-sepsis-in-adults-1qmiufl4t8.pdf

High‐volume haemofiltration for sepsis in adults

Dialysis-dependent chronic kidney disease (CKD) is an expanding problem for healthcare systems worldwide. The prevalence of end-stage renal disease (ESRD) has increased by 20% since 2000 and stands at 1699 per million people in the USA. ESRD is associated with an increased risk of cardiovascular comorbidity, increased severity of cardiovascular disease, and an adjusted all-cause mortality rate that is 6.4-7.8-fold higher than the general population. These patients may present electively or emergently for surgery related to, or remote from, the CKD. In any perioperative setting, the patient with hemodialysis-dependent CKD represents a significant clinical challenge, and successful management of these patients requires effective cooperation and communication between nephrology, anesthesia, and surgical staff. The ESRD patient's nephrologist will have the best knowledge of their medical history, comorbidities, and future management goals and may have been the clinician who instigated the referral for the surgery, e.g., for parathyroidectomy, vascular access surgery, nephrectomy or renal transplantation. As such, they are in an ideal position to contribute to, or coordinate, early preoperative medical optimization of the patient and also to provide advice during postoperative recovery and rehabilitation. In this article, we provide an overview of some of the key aspects of managing these patients successfully during the perioperative period. We propose the integration of cardiopulmonary exercise testing and cardiovascular optimization into the care of these high-risk patients and provide an overview of the importance of maintaining microvascular perfusion and the role of viscosity in preserving the capillary perfusion network.

Perioperative management of the hemodialysis patient.

Background
Severe sepsis and septic shock are leading causes of death in the intensive care unit (ICU). This is despite advances in the management of patients with severe sepsis and septic shock including early recognition, source control, timely and appropriate administration of antimicrobial agents, and goal directed haemodynamic, ventilatory and metabolic therapies. High-volume haemofiltration (HVHF) is a blood purification technique which may improve outcomes in critically ill patients with severe sepsis or septic shock. The technique of HVHF has evolved from renal replacement therapies used to treat acute kidney injury (AKI) in critically ill patients in the ICU.

Objectives
This review assessed whether HVHF improves clinical outcome in adult critically ill patients with sepsis in an ICU setting.

Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2011, Issue 7); MEDLINE (1990 to August 2011), EMBASE (1990 to August 2011); LILACS (1982 to August 2011), Web of Science (1990 to August 2011), CINAHL (1982 to August 2011) and specific websites.

Selection criteria
We included randomized controlled trials (RCTs) and quasi-randomized trials comparing HVHF or high-volume haemodiafiltration to standard or usual dialysis therapy; and RCTs and quasi-randomized trials comparing HVHF or high-volume haemodiafiltration to no similar dialysis therapy. The studies involved adults in critical care units.

Data collection and analysis
Three review authors independently extracted data and assessed trial quality. We sought additional information as required from trialists.

Main results
We included three randomized trials involving 64 participants. Due to the small number of studies and participants, it was not possible to combine data or perform sub-group analyses. One trial reported ICU and 28-day mortality, one trial reported hospital mortality and in the third, the number of deaths stated did not match the quoted mortality rates. No trials reported length of stay in ICU or hospital and one reported organ dysfunction. No adverse events were reported. Overall, the included studies had a low risk of bias.

Authors' conclusions
There were no adverse effects of HVHF reported.There is insufficient evidence to recommend the use of HVHF in critically ill patients with severe sepsis and or septic shock except as interventions being investigated in the setting of a randomized clinical trial. These trials should be large, multi-centred and have clinically relevant outcome measures. Financial implications should also be assessed.

High-volume haemofiltration for sepsis.

High-volume haemofiltration for sepsis (Protocol)

Background Following concerns regarding the emergence of Clostridium difficile infection in 2010, we changed antibiotic prophylaxis in patients undergoing primary hip and knee arthroplasty from cefuroxime to flucloxacillin and single-dose (SD) gentamicin. A subsequent perceived increase in the incidence of post-operative acute kidney injury (AKI) led us to evaluate the AKI incidence between different prophylactic antibiotic regimes used at our centre. Methods We examined the incidence of AKI as defined by Kidney Disease: Improving Global Outcomes criteria in 1588 patients undergoing primary hip or knee arthroplasty from January 2010 to January 2015. Patients received the following prophylactic antibiotic regimes: 8 g flucloxacillin in four divided doses and SD gentamicin 1.5 mg/kg ideal body weight (IBW; maximum dose 120 mg; n = 400), 8 g flucloxacillin alone in four divided doses (n = 400), SD cefuroxime (n = 400), triple-dose (TD) cefuroxime (n = 188) and teicoplanin with SD gentamicin 1.5 mg/kg IBW (n = 200). Results The incidence of AKI was as follows: flucloxacillin and gentamicin (13%); flucloxacillin alone (8.5%); SD cefuroxime (2%); TD cefuroxime (0.5%); and teicoplanin and gentamicin (3%). Of the six patients who developed Stage 3 AKI, all were in the flucloxacillin and gentamicin group. The odds ratio for the development of AKI derived from a binary logistic regression model was highest in the flucloxacillin and gentamicin group [7.79 (95% confidence interval 3.54-17.14), P < 0.0001]. Conclusions Our findings suggest that the use of prophylactic high-dose flucloxacillin and gentamicin should be used with caution in patients undergoing primary hip or knee arthroplasty without a clear advantage in reducing surgical site infections given the association with increased rates of AKI.

Acute kidney injury following prophylactic flucloxacillin and gentamicin in primary hip and knee arthroplasty

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