Publications by authors named "Marlies Ostermann"

176 Publications

Cardiac Surgery Associated AKI Prevention Strategies and Medical Treatment for CSA-AKI.

J Clin Med 2021 Nov 14;10(22). Epub 2021 Nov 14.

Department of Critical Care, King's College London, Guy's & St Thomas' NHS Foundation Trust, London SE1 7EH, UK.

Acute kidney injury (AKI) is common after cardiac surgery. To date, there are no specific pharmacological therapies. In this review, we summarise the existing evidence for prevention and management of cardiac surgery-associated AKI and outline areas for future research. Preoperatively, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers should be withheld and nephrotoxins should be avoided to reduce the risk. Intraoperative strategies include goal-directed therapy with individualised blood pressure management and administration of balanced fluids, the use of circuits with biocompatible coatings, application of minimally invasive extracorporeal circulation, and lung protective ventilation. Postoperative management should be in accordance with current KDIGO AKI recommendations.
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http://dx.doi.org/10.3390/jcm10225285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8618011PMC
November 2021

Extracorporeal Treatment for Gabapentin and Pregabalin Poisoning: Systematic Review and Recommendations From the EXTRIP Workgroup.

Am J Kidney Dis 2021 Nov 16. Epub 2021 Nov 16.

Research Center, CIUSSS du Nord-de-l'île-de-Montréal, Hôpital du Sacré-Coeur de Montréal, University of Montreal, Montreal, Quebec, Canada. Electronic address:

Toxicity from gabapentin and pregabalin overdose is commonly encountered. Treatment is supportive, and the use of extracorporeal treatments (ECTRs) is controversial. The EXTRIP workgroup conducted systematic reviews of the literature and summarized findings following published methods. Thirty-three articles (30 patient reports and 3 pharmacokinetic studies) met the inclusion criteria. High gabapentinoid extracorporeal clearance (>150mL/min) and short elimination half-life (<5 hours) were reported with hemodialysis. The workgroup assessed gabapentin and pregabalin as "dialyzable" for patients with decreased kidney function (quality of the evidence grade as A and B, respectively). Limited clinical data were available (24 patients with gabapentin toxicity and 7 with pregabalin toxicity received ECTR). Severe toxicity, mortality, and sequelae were rare in cases receiving ECTR and in historical controls receiving standard care alone. No clear clinical benefit from ECTR could be identified although major knowledge gaps were acknowledged, as well as costs and harms of ECTR. The EXTRIP workgroup suggests against performing ECTR in addition to standard care rather than standard care alone (weak recommendation, very low quality of evidence) for gabapentinoid poisoning in patients with normal kidney function. If decreased kidney function and coma requiring mechanical ventilation are present, the workgroup suggests performing ECTR in addition to standard care (weak recommendation, very low quality of evidence).
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http://dx.doi.org/10.1053/j.ajkd.2021.06.027DOI Listing
November 2021

Renal replacement therapy in extra-corporeal membrane oxygenation patients: A survey of practices and new insights for future studies.

Anaesth Crit Care Pain Med 2021 Oct 30;40(6):100971. Epub 2021 Oct 30.

Anaesthesiology and Critical Care Medicine, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France; Pathophysiology of Injury-Induced Immunosuppression (Pi3, EA 7426), Université Claude Bernard Lyon 1, Lyon, France.

Background: Patients under extra-corporeal membrane oxygenation (ECMO) are at high risk of developing acute kidney injury and renal replacement therapy (RRT) is frequently needed. The aim of this study was to explore RRT use in ECMO patients, as no recommendations exist in this setting.

Methods: An online questionnaire about RRT management in ECMO patients was sent to the members of the ARCOTHOVA (Anesthésie-Réanimation Coeur-Thorax-Vaisseaux) association and to the GFRUP (Groupe Francophone de Réanimation et Urgences Pédiatriques).

Results: Ninety intensivists from adult ICU and twenty from paediatric ICU responded to the questionnaire. RRT use was common as 67% respondents reported that more than 25% of their ECMO patients needed RRT. RRT indications were similar between centres, with persistent anuria (83%), metabolic acidosis (80%), fluid overload (78%) and hyperkalaemia (80%) being the more prevalent. Continuous renal replacement therapy was the preferred technique (97%). Continuous veno-venous haemofiltration was predominant (64%) over continuous veno-venous haemodiafiltration (21%). Unfractionated heparin was employed as first line choice anticoagulation in 61% and regional citrate anticoagulation in 16%. Integration of RRT device directly into the ECMO circuit was the preferred configuration (40%) while parallel systems with separate catheter were used in 30%. When the integrated approach was chosen, RRT device was most frequently connected with inlet and outlet lines after the ECMO pump (58%) and pressure alarms were encountered for 60% of participants.

Conclusions: Our results highlight the high variability of practice between centres. They suggest the need to compare the integrated and parallel configurations of combining RRT and ECMO.
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http://dx.doi.org/10.1016/j.accpm.2021.100971DOI Listing
October 2021

Acute kidney injury in patients treated with immune checkpoint inhibitors.

J Immunother Cancer 2021 10;9(10)

Division of Hematology-Oncology, VAGLAHS, Department of Medicine, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, California, USA.

Background: Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer.

Methods: We collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI.

Results: ICPi-AKI occurred at a median of 16 weeks (IQR 8-32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3-10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI.

Conclusions: Patients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery.
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http://dx.doi.org/10.1136/jitc-2021-003467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8496384PMC
October 2021

Discharge Documentation and Follow-Up of Critically Ill Patients With Acute Kidney Injury Treated With Kidney Replacement Therapy: A Retrospective Cohort Study.

Front Med (Lausanne) 2021 14;8:710228. Epub 2021 Sep 14.

Department of Critical Care, King's College London, Guy's and St Thomas' Hospital National Health Service Foundation Trust, London, United Kingdom.

Leading organisations recommend follow-up of acute kidney injury (AKI) survivors, as these patients are at risk of long-term complications and increased mortality. Information transfer between specialties and from tertiary to primary care is essential to ensure timely and appropriate follow-up. Our aim was to examine the association between completeness of discharge documentation and subsequent follow-up of AKI survivors who received kidney replacement therapy (KRT) in the Intensive Care Unit (ICU). We retrospectively analysed the data of 433 patients who had KRT for AKI during ICU admission in a tertiary care centre in the UK between June 2017 and May 2018 and identified patients who were discharged from hospital alive. Patients with pre-existing end-stage kidney disease and patients who were transferred from hospitals outside the catchment area were excluded. The primary objective was to assess the completeness of discharge documentation from critical care and hospital; secondary objectives were to determine cardiovascular medications reconciliation after AKI, and to investigate kidney care and outcomes at 1 year. The development of AKI and the need for KRT were mentioned in 85 and 82% of critical care discharge letters, respectively. Monitoring of kidney function post-discharge was recommended in 51.6% of critical care and 36.3% of hospital discharge summaries. Among 35 patients who were prescribed renin-angiotensin-aldosterone system inhibitors before hospitalisation, 15 (42.9%) were not re-started before discharge from hospital. At 3 months, creatinine and urine protein were measured in 88.2 and 11.8% of survivors, respectively. The prevalence of chronic kidney disease stage III or worse increased from 27.2% pre-hospitalisation to 54.9% at 1 year ( < 0.001). Our data demonstrate that discharge summaries of patients with AKI who received KRT lacked essential information. Furthermore, even in patients with appropriate documentation, renal follow-up was poor suggesting the need for more education and streamlined care pathways.
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http://dx.doi.org/10.3389/fmed.2021.710228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8476795PMC
September 2021

Definitions of acute renal dysfunction: an evolving clinical and biomarker paradigm.

Curr Opin Crit Care 2021 Dec;27(6):553-559

Department of Critical Care, King's College London, Guy's & St Thomas' NHS Foundation Trust, London, UK.

Purpose Of Review: The current definition and classification of acute kidney injury (AKI) has limitations and shortcomings, which impact clinical management. The aim of this review is to highlight recent advances in our understanding of the pathophysiology and epidemiology of AKI, which impacts management and offers opportunities.

Recent Findings: Kidney damage varies according to the type of primary insult, secondary effects and mitigating responses and leads to distinct molecular, cellular and functional changes. Different sub-types of AKI with varying clinical phenotypes, recovery patterns and responses to therapeutic interventions have been identified. New tools to identify and characterize these AKI sub-types are available with the potential opportunity for individualized timely aetiology-based management of AKI.

Summary: The identification of different sub-phenotypes of AKI based on genetic, molecular, cellular and functional pathophysiological changes following potential nephrotoxic exposures is possible with new technologies. This offers opportunities for personalized management of AKI and supports the call for a refinement of the existing AKI criteria.
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http://dx.doi.org/10.1097/MCC.0000000000000886DOI Listing
December 2021

Biomarker-Based Management of AKI: Fact or Fantasy?

Nephron 2021 Aug 26:1-7. Epub 2021 Aug 26.

Department of Critical Care, King's College London, Guy's & St Thomas' NHS Foundation Trust, London, United Kingdom.

New biomarkers for acute kidney injury (AKI) have improved our understanding of the etiology and pathogenesis of AKI. Depending on their origin, function, and kinetic profile, biomarkers have a role in screening, diagnosis, prognostication, and monitoring of AKI. This offers opportunities to improve the management of AKI, but concerns and limitations remain. In this review, we summarize the current role of new AKI biomarkers in the management of AKI and outline some of the ongoing limitations and challenges.
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http://dx.doi.org/10.1159/000518365DOI Listing
August 2021

Acute kidney injury in ECMO patients.

Crit Care 2021 08 31;25(1):313. Epub 2021 Aug 31.

Department of Critical Care, King's College London, Guy's and St Thomas' NHS Foundation Trust, London, UK.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2021. Other selected articles can be found online at  https://www.biomedcentral.com/collections/annualupdate2021 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from  https://link.springer.com/bookseries/8901 .
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http://dx.doi.org/10.1186/s13054-021-03676-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405346PMC
August 2021

Do ventilatory parameters influence outcome in patients with severe acute respiratory infection? Secondary analysis of an international, multicentre14-day inception cohort study.

J Crit Care 2021 12 27;66:78-85. Epub 2021 Aug 27.

Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada; Keenan Research Centre, Li KaShing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada.

Purpose: To investigate the possible association between ventilatory settings on the first day of invasive mechanical ventilation (IMV) and mortality in patients admitted to the intensive care unit (ICU) with severe acute respiratory infection (SARI).

Materials And Methods: In this pre-planned sub-study of a prospective, multicentre observational study, 441 patients with SARI who received controlled IMV during the ICU stay were included in the analysis.

Results: ICU and hospital mortality rates were 23.1 and 28.1%, respectively. In multivariable analysis, tidal volume and respiratory rate on the first day of IMV were not associated with an increased risk of death; however, higher driving pressure (DP: odds ratio (OR) 1.05; 95% confidence interval (CI): 1.01-1.1, p = 0.011), plateau pressure (Pplat) (OR 1.08; 95% CI: 1.04-1.13, p < 0.001) and positive end-expiratory pressure (PEEP) (OR 1.13; 95% CI: 1.03-1.24, p = 0.006) were independently associated with in-hospital mortality. In subgroup analysis, in hypoxemic patients and in patients with acute respiratory distress syndrome (ARDS), higher DP, Pplat, and PEEP were associated with increased risk of in-hospital death.

Conclusions: In patients with SARI receiving IMV, higher DP, Pplat and PEEP, and not tidal volume, were associated with a higher risk of in-hospital death, especially in those with hypoxemia or ARDS.
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http://dx.doi.org/10.1016/j.jcrc.2021.08.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394083PMC
December 2021

Acute kidney injury prevalence, progression and long-term outcomes in critically ill patients with COVID-19: a cohort study.

Ann Intensive Care 2021 Aug 6;11(1):123. Epub 2021 Aug 6.

Department of Critical Care, Guy's & St Thomas' Hospital NHS Foundation Hospital, 249 Westminster Bridge Road, London, SE1 7EH, UK.

Background: There are limited data on acute kidney injury (AKI) progression and long-term outcomes in critically ill patients with coronavirus disease-19 (COVID-19). We aimed to describe the prevalence and risk factors for development of AKI, its subsequent clinical course and AKI progression, as well as renal recovery or dialysis dependence and survival in this group of patients.

Methods: This was a retrospective observational study in an expanded tertiary care intensive care unit in London, United Kingdom. Critically ill patients admitted to ICU between 1st March 2020 and 31st July 2020 with confirmed SARS-COV2 infection were included. Analysis of baseline characteristics, organ support, COVID-19 associated therapies and their association with mortality and outcomes at 90 days was performed.

Results: Of 313 patients (70% male, mean age 54.5 ± 13.9 years), 240 (76.7%) developed AKI within 14 days after ICU admission: 63 (20.1%) stage 1, 41 (13.1%) stage 2, 136 (43.5%) stage 3. 113 (36.1%) patients presented with AKI on ICU admission. Progression to AKI stage 2/3 occurred in 36%. Risk factors for AKI progression were mechanical ventilation [HR (hazard ratio) 4.11; 95% confidence interval (CI) 1.61-10.49] and positive fluid balance [HR 1.21 (95% CI 1.11-1.31)], while steroid therapy was associated with a reduction in AKI progression (HR 0.73 [95% CI 0.55-0.97]). Kidney replacement therapy (KRT) was initiated in 31.9%. AKI patients had a higher 90-day mortality than non-AKI patients (34% vs. 14%; p < 0.001). Dialysis dependence was 5% at hospital discharge and 4% at 90 days. Renal recovery was identified in 81.6% of survivors at discharge and in 90.9% at 90 days. At 3 months, 16% of all AKI survivors had chronic kidney disease (CKD); among those without renal recovery, the CKD incidence was 44%.

Conclusions: During the first COVID-19 wave, AKI was highly prevalent among severely ill COVID-19 patients with a third progressing to severe AKI requiring KRT. The risk of developing CKD was high. This study identifies factors modifying AKI progression, including a potentially protective effect of steroid therapy. Recognition of risk factors and monitoring of renal function post-discharge might help guide future practice and follow-up management strategies. Trial registration NCT04445259.
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http://dx.doi.org/10.1186/s13613-021-00914-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343342PMC
August 2021

Acute kidney injury in the critically ill: an updated review on pathophysiology and management.

Intensive Care Med 2021 Aug 2;47(8):835-850. Epub 2021 Jul 2.

Clinical Department and Laboratory of Intensive Care Medicine, Division of Cellular and Molecular Medicine, KU Leuven University, Herestraat 49, B3000, Leuven, Belgium.

Acute kidney injury (AKI) is now recognized as a heterogeneous syndrome that not only affects acute morbidity and mortality, but also a patient's long-term prognosis. In this narrative review, an update on various aspects of AKI in critically ill patients will be provided. Focus will be on prediction and early detection of AKI (e.g., the role of biomarkers to identify high-risk patients and the use of machine learning to predict AKI), aspects of pathophysiology and progress in the recognition of different phenotypes of AKI, as well as an update on nephrotoxicity and organ cross-talk. In addition, prevention of AKI (focusing on fluid management, kidney perfusion pressure, and the choice of vasopressor) and supportive treatment of AKI is discussed. Finally, post-AKI risk of long-term sequelae including incident or progression of chronic kidney disease, cardiovascular events and mortality, will be addressed.
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http://dx.doi.org/10.1007/s00134-021-06454-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249842PMC
August 2021

Nutrients and micronutrients at risk during renal replacement therapy: a scoping review.

Curr Opin Crit Care 2021 08;27(4):367-377

Department of Anesthesiology and Surgery, Duke University School of Medicine, Durham, North Carolina, USA.

Purpose Of Review: Malnutrition is frequent in patients with acute kidney injury. Nutrient clearance during renal replacement therapy (RRT) potentially contributes to this complication. Although losses of amino acid, trace elements and vitamins have been described, there is no clear guidance regarding the role of micronutrient supplementation.

Recent Findings: A scoping review was conducted with the aim to review the existing literature on micronutrients status during RRT: 35 publications including data on effluent losses and blood concentrations were considered relevant and analysed. For completeness, we also included data on amino acids. Among trace elements, negative balances have been shown for copper and selenium: low blood levels seem to indicate potential deficiency. Smaller size water soluble vitamins were found in the effluent, but not larger size liposoluble vitamins. Low blood values were frequently reported for thiamine, folate and vitamin C, as well as for carnitine. All amino acids were detectable in effluent fluid. Duration of RRT was associated with decreasing blood values.

Summary: Losses of several micronutrients and amino acids associated with low blood levels represent a real risk of deficiency for vitamins B1 and C, copper and selenium: they should be monitored in prolonged RRT. Further Research is urgently required as the data are insufficient to generate strong conclusions and prescription recommendations for clinical practice.
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http://dx.doi.org/10.1097/MCC.0000000000000851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270509PMC
August 2021

Perioperative use of serum creatinine and postoperative acute kidney injury: a single-centre, observational retrospective study to explore physicians' perception and practice.

Perioper Med (Lond) 2021 May 25;10(1):13. Epub 2021 May 25.

Department of Health Sciences, Section of Anaesthesiology, Intensive Care and Pain Medicine, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy.

Background: Postoperative acute kidney injury (PO-AKI) is a leading cause of short- and long-term morbidity and mortality, as well as progression to chronic kidney disease (CKD). The aim of this study was to explore the physicians' attitude toward the use of perioperative serum creatinine (sCr) for the identification of patients at risk for PO-AKI and long-term CKD. We also evaluated the incidence and risk factors associated with PO-AKI and renal function deterioration in patients undergoing major surgery for malignant disease.

Methods: Adult oncological patients who underwent major abdominal surgery from November 2016 to February 2017 were considered for this single-centre, observational retrospective study. Routinely available sCr values were used to define AKI in the first three postoperative days. Long-term kidney dysfunction (LT-KDys) was defined as a reduction in the estimated glomerular filtration rate by more than 10 ml/min/m at 12 months postoperatively. A questionnaire was administered to 125 physicians caring for the enrolled patients to collect information on local attitudes regarding the use of sCr perioperatively and its relationship with PO-AKI.

Results: A total of 423 patients were observed. sCr was not available in 59 patients (13.9%); the remaining 364 (86.1%) had at least one sCr value measured to allow for detection of postoperative kidney impairment. Among these, PO-AKI was diagnosed in 8.2% of cases. Of the 334 patients who had a sCr result available at 12-month follow-up, 56 (16.8%) developed LT-KDys. Data on long-term kidney function were not available for 21% of patients. Interestingly, 33 of 423 patients (7.8%) did not have a sCr result available in the immediate postoperative period or long term. All the physicians who participated in the survey (83 out of 125) recognised that postoperative assessment of sCr is required after major oncological abdominal surgery, particularly in those patients at high risk for PO-AKI and LT-KDys.

Conclusion: PO-AKI after major surgery for malignant disease is common, but clinical practice of measuring sCr is variable. As a result, the exact incidence of PO-AKI and long-term renal prognosis are unclear, including in high-risk patients.

Trial Registration: ClinicalTrials.gov , NCT04341974 .
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http://dx.doi.org/10.1186/s13741-021-00184-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145835PMC
May 2021

Postoperative acute kidney injury in adult non-cardiac surgery: joint consensus report of the Acute Disease Quality Initiative and PeriOperative Quality Initiative.

Nat Rev Nephrol 2021 09 11;17(9):605-618. Epub 2021 May 11.

Center for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

Postoperative acute kidney injury (PO-AKI) is a common complication of major surgery that is strongly associated with short-term surgical complications and long-term adverse outcomes, including increased risk of chronic kidney disease, cardiovascular events and death. Risk factors for PO-AKI include older age and comorbid diseases such as chronic kidney disease and diabetes mellitus. PO-AKI is best defined as AKI occurring within 7 days of an operative intervention using the Kidney Disease Improving Global Outcomes (KDIGO) definition of AKI; however, additional prognostic information may be gained from detailed clinical assessment and other diagnostic investigations in the form of a focused kidney health assessment (KHA). Prevention of PO-AKI is largely based on identification of high baseline risk, monitoring and reduction of nephrotoxic insults, whereas treatment involves the application of a bundle of interventions to avoid secondary kidney injury and mitigate the severity of AKI. As PO-AKI is strongly associated with long-term adverse outcomes, some form of follow-up KHA is essential; however, the form and location of this will be dictated by the nature and severity of the AKI. In this Consensus Statement, we provide graded recommendations for AKI after non-cardiac surgery and highlight priorities for future research.
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http://dx.doi.org/10.1038/s41581-021-00418-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8367817PMC
September 2021

Long-term kidney function of patients discharged from hospital after an intensive care admission: observational cohort study.

Sci Rep 2021 05 11;11(1):9928. Epub 2021 May 11.

Department of Critical Care, King's College London, Guy's and St Thomas' NHS Foundation Trust, London, SE1 7EH, UK.

The long-term trajectory of kidney function recovery or decline for survivors of critical illness is incompletely understood. Characterising changes in kidney function after critical illness and associated episodes of acute kidney injury (AKI), could inform strategies to monitor and treat new or progressive chronic kidney disease. We assessed changes in estimated glomerular filtration rate (eGFR) and impact of AKI for 1301 critical care survivors with 5291 eGFR measurements (median 3 [IQR 2, 5] per patient) between hospital discharge (2004-2008) and end of 7 years of follow-up. Linear mixed effects models showed initial decline in eGFR over the first 6 months was greatest in patients without AKI (- 9.5%, 95% CI - 11.5% to - 7.4%) and with mild AKI (- 12.3%, CI - 15.1% to - 9.4%) and least in patients with moderate-severe AKI (- 4.3%, CI - 7.0% to - 1.4%). However, compared to patients without AKI, hospital discharge eGFR was lowest for the moderate-severe AKI group (median 61 [37, 96] vs 101 [78, 120] ml/min/1.73m) and two thirds (66.5%, CI 59.8-72.6% vs 9.2%, CI 6.8-12.4%) had an eGFR of < 60 ml/min/1.73m through to 7 years after discharge. Kidney function trajectory after critical care discharge follows a distinctive pattern of initial drop then sustained decline. Regardless of AKI severity, this evidence suggests follow-up should incorporate monitoring of eGFR in the early months after hospital discharge.
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http://dx.doi.org/10.1038/s41598-021-89454-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113423PMC
May 2021

Restrictive fluid management versus usual care in acute kidney injury (REVERSE-AKI): a pilot randomized controlled feasibility trial.

Intensive Care Med 2021 06 7;47(6):665-673. Epub 2021 May 7.

Department of Intensive Care, Austin Hospital, Melbourne, Australia.

Purpose: We compared a restrictive fluid management strategy to usual care among critically ill patients with acute kidney injury (AKI) who had received initial fluid resuscitation.

Methods: This multicenter feasibility trial randomized 100 AKI patients 1:1 in seven ICUs in Europe and Australia. Restrictive fluid management included targeting negative or neutral daily fluid balance by minimizing fluid input and/or enhancing urine output with diuretics administered at the discretion of the clinician. Fluid boluses were administered as clinically indicated. The primary endpoint was cumulative fluid balance 72 h from randomization.

Results: Mean (SD) cumulative fluid balance at 72 h from randomization was - 1080 mL (2003 mL) in the restrictive fluid management arm and 61 mL (3131 mL) in the usual care arm, mean difference (95% CI) - 1148 mL (- 2200 to - 96) mL, P = 0.033. Median [IQR] duration of AKI was 2 [1-3] and 3 [2-7] days, respectively (median difference - 1.0 [- 3.0 to 0.0], P = 0.071). Altogether, 6 out of 46 (13%) patients in the restrictive fluid management arm and 15 out of 50 (30%) in the usual care arm received renal replacement therapy (RR 0.42; 95% CI 0.16-0.91), P = 0.043. Cumulative fluid balance at 24 h and 7 days was lower in the restrictive fluid management arm. The dose of diuretics was not different between the groups. Adverse events occurred more frequently in the usual care arm.

Conclusions: In critically ill patients with AKI, a restrictive fluid management regimen resulted in lower cumulative fluid balance and less adverse events compared to usual care. Larger trials of this intervention are justified.
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http://dx.doi.org/10.1007/s00134-021-06401-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195764PMC
June 2021

Nutritional assessment and support during continuous renal replacement therapy.

Semin Dial 2021 Nov 28;34(6):449-456. Epub 2021 Apr 28.

Department of Medicine, UCSD Medical Center, University of California, San Diego, CA, USA.

Malnutrition is highly prevalent in patients with acute kidney injury, especially in those receiving renal replacement therapy (RRT). For the assessment of nutritional status, a combination of screening tools, anthropometry, and laboratory parameters is recommended rather than a single test. To avoid underfeeding and overfeeding during RRT, energy expenditure should be measured by indirect calorimetry or calculated using predictive equations. Nitrogen balance should be periodically measured to assess the degree of catabolism and to evaluate protein intake. However, there is limited data for nutritional targets specifically for patients on RRT, such as protein intake. The composition of commercial solutions for continuous renal replacement therapy (CRRT) varies. CRRT itself can be associated with both, nutrient losses into the effluent fluid and caloric gain from dextrose, lactate, and citrate. The role of micronutrient supplementation, and potential use of micronutrient enriched CRRT solutions in this setting is unknown, too. This review provides an overview of existing knowledge and uncertainties related to nutritional aspects in patients on CRRT and emphasizes the need for more research in this area.
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http://dx.doi.org/10.1111/sdi.12973DOI Listing
November 2021

FGF23 ameliorates ischemia-reperfusion induced acute kidney injury via modulation of endothelial progenitor cells: targeting SDF-1/CXCR4 signaling.

Cell Death Dis 2021 04 17;12(5):409. Epub 2021 Apr 17.

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.

The levels of fibroblast growth factor 23 (FGF23) rapidly increases after acute kidney injury (AKI). However, the role of FGF23 in AKI is still unclear. Here, we observe that pretreatment with FGF23 protein into ischemia-reperfusion induced AKI mice ameliorates kidney injury by promoting renal tubular regeneration, proliferation, vascular repair, and attenuating tubular damage. In vitro assays demonstrate that SDF-1 induces upregulation of its receptor CXCR4 in endothelial progenitor cells (EPCs) via a non-canonical NF-κB signaling pathway. FGF23 crosstalks with the SDF-1/CXCR4 signaling and abrogates SDF-1-induced EPC senescence and migration, but not angiogenesis, in a Klotho-independent manner. The downregulated pro-angiogenic IL-6, IL-8, and VEGF-A expressions after SDF-1 infusion are rescued after adding FGF23. Diminished therapeutic ability of SDF-1-treated EPCs is counteracted by FGF23 in a SCID mouse in vivo AKI model. Together, these data highlight a revolutionary and important role that FGF23 plays in the nephroprotection of IR-AKI.
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http://dx.doi.org/10.1038/s41419-021-03693-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053200PMC
April 2021

Wait and see for acute dialysis: but for how long?

Lancet 2021 Apr;397(10281):1241-1243

Department of Critical Care, King's College London, Guy's & St Thomas' NHS Foundation Trust, London SE1 7EH, UK; Division of Nephrology and Excellence Centre for Critical Care Nephrology, King Chulalongkorn Memorial Hospital, Bangkok, Thailand; Critical Care Nephrology Research Unit, Chulalongkorn University, Bangkok, Thailand.

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http://dx.doi.org/10.1016/S0140-6736(21)00466-9DOI Listing
April 2021

Predicting AKI: do we have the necessary tools?

Minerva Anestesiol 2021 04 10;87(4):397-399. Epub 2021 Mar 10.

Department of Critical Care, King's College London, Guy's and St. Thomas' NHS Foundation Trust, London, UK.

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http://dx.doi.org/10.23736/S0375-9393.21.15635-4DOI Listing
April 2021

Prevention of Cardiac Surgery-Associated Acute Kidney Injury by Implementing the KDIGO Guidelines in High-Risk Patients Identified by Biomarkers: The PrevAKI-Multicenter Randomized Controlled Trial.

Anesth Analg 2021 08;133(2):292-302

From the Department of Anesthesiology, Intensive Care Medicine and Pain Medicine, University Hospital Münster, Münster, Germany.

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.
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http://dx.doi.org/10.1213/ANE.0000000000005458DOI Listing
August 2021

Surviving Sepsis Campaign Guidelines on the Management of Adults With Coronavirus Disease 2019 (COVID-19) in the ICU: First Update.

Crit Care Med 2021 03;49(3):e219-e234

Warren Alpert School of Medicine at Brown University, Providence, RI.

Background: The coronavirus disease 2019 pandemic continues to affect millions worldwide. Given the rapidly growing evidence base, we implemented a living guideline model to provide guidance on the management of patients with severe or critical coronavirus disease 2019 in the ICU.

Methods: The Surviving Sepsis Campaign Coronavirus Disease 2019 panel has expanded to include 43 experts from 14 countries; all panel members completed an electronic conflict-of-interest disclosure form. In this update, the panel addressed nine questions relevant to managing severe or critical coronavirus disease 2019 in the ICU. We used the World Health Organization's definition of severe and critical coronavirus disease 2019. The systematic reviews team searched the literature for relevant evidence, aiming to identify systematic reviews and clinical trials. When appropriate, we performed a random-effects meta-analysis to summarize treatment effects. We assessed the quality of the evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach, then used the evidence-to-decision framework to generate recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility.

Results: The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued nine statements (three new and six updated) related to ICU patients with severe or critical coronavirus disease 2019. For severe or critical coronavirus disease 2019, the panel strongly recommends using systemic corticosteroids and venous thromboprophylaxis but strongly recommends against using hydroxychloroquine. In addition, the panel suggests using dexamethasone (compared with other corticosteroids) and suggests against using convalescent plasma and therapeutic anticoagulation outside clinical trials. The Surviving Sepsis Campaign Coronavirus Diease 2019 panel suggests using remdesivir in nonventilated patients with severe coronavirus disease 2019 and suggests against starting remdesivir in patients with critical coronavirus disease 2019 outside clinical trials. Because of insufficient evidence, the panel did not issue a recommendation on the use of awake prone positioning.

Conclusion: The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued several recommendations to guide healthcare professionals caring for adults with critical or severe coronavirus disease 2019 in the ICU. Based on a living guideline model the recommendations will be updated as new evidence becomes available.
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http://dx.doi.org/10.1097/CCM.0000000000004899DOI Listing
March 2021

Association of plasma and urine NGAL with acute kidney injury after elective colorectal surgery: A cohort study.

Ann Med Surg (Lond) 2021 Feb 22;62:315-322. Epub 2021 Jan 22.

Department of Colorectal Surgery, Guy's & St Thomas' Hospital, London, UK.

Background: Acute kidney injury (AKI) is common in surgical patients. We aimed to investigate the validity of plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) in the detection of AKI and prediction of outcomes in patients undergoing major colorectal surgery.

Materials And Methods: This was a pre-specified post-hoc analysis of a randomized controlled trial comparing oesophageal doppler and Lithium dilution cardiac output monitoring in high risk patients undergoing major colorectal surgery as part of an Enhanced Recovery After Surgery protocol in a tertiary care hospital. Plasma and urine samples for NGAL measurement were taken before surgery (T1), immediately after surgery (T2), and on postoperative day 1 (T3). AKI was defined according to the KDIGO criteria.

Results: A total of 89 patients were included of whom 12 (13.5%) developed AKI. Plasma NGAL significantly increased from T1 to T3 in both AKI (p < 0.001) and non-AKI (p = 0.048) patients, while urine NGAL did not change over time. There were no significant differences in plasma and urine NGAL in patients with and without AKI at all time points. Postoperative day 1 urine NGAL concentrations were significantly higher in non-survivors than survivors (41.2 versus 25 ng/mL, p = 0.026). One-year mortality was significantly higher in AKI patients with a raised urine NGAL compared to AKI patients without elevated urine NGAL levels.

Conclusions: Plasma and urine NGAL poorly predicted AKI post-colorectal surgery. Non-survivors had higher urine NGAL results. More research is required to explore the association between NGAL and long-term outcomes.
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http://dx.doi.org/10.1016/j.amsu.2021.01.060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847815PMC
February 2021

Clearance of inflammatory cytokines in patients with septic acute kidney injury during renal replacement therapy using the EMiC2 filter (Clic-AKI study).

Crit Care 2021 01 28;25(1):39. Epub 2021 Jan 28.

Department of Critical Care, Guy's and St Thomas' Hospital, King's College London, NHS Foundation Trust, 249 Westminster Bridge Road, London, SE1 7EH, UK.

Background: The EMiC2 membrane is a medium cut-off haemofilter (45 kiloDalton). Little is known regarding its efficacy in eliminating medium-sized cytokines in sepsis. This study aimed to explore the effects of continuous veno-venous haemodialysis (CVVHD) using the EMiC2 filter on cytokine clearance.

Methods: This was a prospective observational study conducted in critically ill patients with sepsis and acute kidney injury requiring kidney replacement therapy. We measured concentrations of 12 cytokines [Interleukin (IL) IL-1β, IL-1α, IL-2, IL-4, IL-6, IL-8, IL-10, interferon (IFN)-γ, tumour necrosis factor (TNF)-α, vascular endothelial growth factor, monocyte chemoattractant protein (MCP)-1, epidermal growth factor (EGF)] in plasma at baseline (T0) and pre- and post-dialyzer at 1, 6, 24, and 48 h after CVVHD initiation and in the effluent fluid at corresponding time points. Outcomes were the effluent and adsorptive clearance rates, mass balances, and changes in serial serum concentrations.

Results: Twelve patients were included in the final analysis. All cytokines except EGF concentrations declined over 48 h (p < 0.001). The effluent clearance rates were variable and ranged from negligible values for IL-2, IFN-γ, IL-1α, IL-1β, and EGF, to 19.0 ml/min for TNF-α. Negative or minimal adsorption was observed. The effluent and adsorptive clearance rates remained steady over time. The percentage of cytokine removal was low for most cytokines throughout the 48-h period.

Conclusion: EMiC2-CVVHD achieved modest removal of most cytokines and demonstrated small to no adsorptive capacity despite a decline in plasma cytokine concentrations. This suggests that changes in plasma cytokine concentrations may not be solely influenced by extracorporeal removal.

Trial Registration: NCT03231748, registered on 27th July 2017.
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http://dx.doi.org/10.1186/s13054-021-03476-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845048PMC
January 2021

Net ultrafiltration prescription survey in Europe.

BMC Nephrol 2020 12 1;21(1):522. Epub 2020 Dec 1.

Department of Critical Care, King's College London, Guy's & St Thomas' Hospital, NHS Foundation Trust, London, SE1 7EH, UK.

Background: Fluid overload is common in patients in the intensive care unit (ICU) and ultrafiltration (UF) is frequently required. There is lack of guidance on optimal UF practice. We aimed to explore patterns of UF practice, barriers to achieving UF targets, and concerns related to UF practice among practitioners working in Europe.

Methods: This was a sub-study of an international open survey with focus on adult intensivists and nephrologists, advanced practice providers, and ICU and dialysis nurses working in Europe.

Results: Four hundred eighty-five practitioners (75% intensivists) from 31 countries completed the survey. The most common criteria for UF initiation was persistent oliguria/anuria (45.6%), followed by pulmonary edema (16.7%). Continuous renal replacement therapy was the preferred initial modality (90.0%). The median initial and maximal rate of net ultrafiltration (UF) prescription in hemodynamically stable patients were 149 mL/hr. (IQR 100-200) and 300 mL/hr. (IQR 201-352), respectively, compared to a median UF rate of 98 mL/hr. (IQR 51-108) in hemodynamically unstable patients and varied significantly between countries. Two-thirds of nurses and 15.5% of physicians reported assessing fluid balance hourly. When hemodynamic instability occurred, 70.1% of practitioners reported decreasing the rate of fluid removal, followed by starting or increasing the dose of a vasopressor (51.3%). Most respondents (90.7%) believed in early fluid removal and expressed willingness to participate in a study comparing protocol-based fluid removal versus usual care.

Conclusions: There was a significant variation in UF practice and perception among practitioners in Europe. Future research should focus on identifying the best strategies of prescribing and managing ultrafiltration in critically ill patients.
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http://dx.doi.org/10.1186/s12882-020-02184-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706211PMC
December 2020
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