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Purpose: During critical illness interpretation of serum creatinine is affected by non-steady state conditions, reduced creatinine generation, and altered distribution. We evaluated healthcare professionals' ability to adjudicate underlying kidney function, based on simulated creatinine values., Methods: We developed an online survey, incorporating 12 scenarios with simulated trajectories of creatinine based on profiles of muscle mass, GFR and fluid balance using bespoke kinetic modelling. Participants predicted true underlying GFR (<5, 5-14, 15-29, 30-44, 45-59, 60-90, >90 ml.min -1 .1.73 m -2 ) and AKI stage (stages 1-3, defined as 33 %, 50 %, 66 % decrease in GFR from baseline) during the first 7-days and at ICU discharge., Results: 100 of 103 respondents from 16 countries, 94 completed 1 or more scenarios. 43(43 %) were senior physicians, 74(74 %) critical care and 31(31 %) nephrology physicians. Over the first 7-days, true GFR was correctly estimated 43 % of the time and underlying AKI stage in 57 % of patient days. At ICU discharge GFR was predicted 35 % of the time. At all timepoints, over and under-estimation of GFR was observed., Conclusion: Participants displayed marked variation in estimation of kidney function, suggesting difficulty in accounting for multiple confounders. There is need for alternative, unbiased measures of kidney function in critical illness to avoid misclassifying kidney disease., Competing Interests: Declaration of competing interest Dr. Prowle has recent consultancy agreements with Jaffron Biomedical Co Ltd., Paion Ltd., Nephrolyx GmbH, Mission Therapeutics, Vantive Inc. and Nikkiso Europe GmbH. Dr. Prowle has received speaker's fees and hospitality from Vantive Inc., BBraun and Nikkiso Europe. Dr. Prowle has received research support from Astute Medical a Biomerieux company and Jaffron Biomedical Co Ltd. Dr. Prowle serves on a DMSB for Novartis., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Continuous renal replacement therapy (CRRT) dose is usually fixed and primarily weight-based. Whilst this is safe, theoretically, underdosing or overdosing may occur in those requiring acute versus maintenance CRRT respectively. We have developed a dynamic dosing protocol for CRRT which individualises and updates dosing according to biochemistry. Here we describe the protocol and compare it to a fixed dose protocol to evaluate its safety and effectiveness., Methods: We conducted a service evaluation of this novel protocol using data from consecutive non-COVID-19 admissions receiving CRRT within Barts Health NHS trust, United Kingdom (UK). Fifty admissions using the dynamic protocol were compared to historically collected data from 108 admissions who used the fixed protocol. Acute and maintenance CRRT subgroups were analysed., Results: For the dynamic protocol 49 patients were treated with 135 CRRT circuits. One patient had two admissions. Protocol compliance (compared in one ICU) was 76% (dynamic) vs 61% (fixed) ( p  < 0.05). For the dynamic versus fixed protocol, median CRRT lifespan censored for reasons other than clotting was: 56 h vs 58 h RCA (ns), 27 h versus 20 h heparin (ns) and 79 h versus 22 h no anticoagulation ( p  < 0.05). The dynamic vs fixed protocol average CRRT dose was: 30 ml/kg/h (14-57) vs 26 ml/kg/h (20-62) ( p  < 0.05). The dynamic protocol generated a similar rate of increase of bicarbonate in an acute phase (RCA: 0.2 mmol/l/h vs 0.21 mmol/l/h, ns) and maintained a more stable level in a maintenance phase (RCA: -0.01 mmol/l/h vs 0.07 mmol/l/h, p  < 0.05)., Discussion: Dynamic dosing for CRRT in this institution was safe and may lead to more tailored maintenance of biochemical homoeostasis., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Jack Eldridge, Aroon Bhardwaj Shah, Yize Wan and Susana Lucena-Amaro have no conflicts of interest to declare. Christopher Kirwan has received speaker fees from Baxter Inc, B. Braun Medical Ltd, Fresenius Medical Care and Nikkiso. He has received an unrestricted educational grant from Nikkiso and consultancy fees from Nikkiso and B. Braun Medical Ltd. John Prowle has received hospitality from B. Braun Medical Ltd. and speakers fees from Fresenius Medical Care, Nikkiso Europe GmbH and Baxter Inc. He has performed paid consultancy for Nikkiso Europe GmbH, Baxter Inc and Jafron Biomedical Co Ltd and has received an unrestricted research grant from Jafron Biomedical Co Ltd., (© The Intensive Care Society 2023.)

Background: Post-operative acute kidney injury (PO-AKI) is a common surgical complication consistently associated with subsequent morbidity and mortality. Prior kidney dysfunction is a major risk factor for PO-AKI, however it is unclear whether serum creatinine, the conventional kidney function marker, is optimal in this population. Serum cystatin C is a kidney function marker less affected by body composition and might provide better prognostic information in surgical patients., Methods: This was a pre-defined, secondary analysis of a multi-centre prospective cohort study of pre-operative functional capacity. Participants were aged ≥40 years, undergoing non-cardiac surgery. We assessed the association of pre-operative estimated glomerular filtration rate (eGFR) calculated using both serum creatinine and serum cystatin C with PO-AKI within 3 days after surgery, defined by KDIGO creatinine changes. The adjusted analysis accounted for established AKI risk factors., Results: A total of 1347 participants were included (median age 65 years, interquartile range 56-71), of whom 775 (58%) were male. A total of 82/1347 (6%) patients developed PO-AKI. These patients were older, had higher prevalence of cardiovascular disease and related medication, were more likely to have intra-abdominal procedures, had more intraoperative transfusion, and were more likely to be dead at 1 year after surgery 6/82 (7.3%) vs 33/1265 (2.7%) ( P  = .038). Pre-operative eGFR was lower in AKI than non-AKI patients using both creatinine and cystatin C. When both measurements were considered in a single age- and sex-adjusted model, eGFR-Cysc was strongly associated with PO-AKI, with increasing risk of AKI as eGFR-Cysc decreased below 90, while eGFR-Cr was no longer significantly associated., Conclusions: Data from over 1000 prospectively recruited surgical patients confirms pre-operative kidney function as major risk factor for PO-AKI. Of the kidney function markers available, compared with creatinine, cystatin C had greater strength of association with PO-AKI and merits further assessment in pre-operative assessment of surgical risk., Competing Interests: J.R.P. has received honoraria from Paion Ltd, Baxter Inc., Biomerieux SA and Nikkiso Europe GmbH; he is a scientific advisor for Mission Therapeutics Ltd, Jafron Biomedical Co. Ltd and Nephrolyx GmbH, and serves on a Data Monitoring and Safety Board for Novartis Inc.; he is a specialty editor for the Clinical Kidney Journal and Blood Purification. B.H.C. and D.N.W. are supported in part by Merit Awards from the Department of Anesthesiology and Pain Medicine at the University of Toronto. D.N.W. is supported in part by the Endowed Chair in Translational Anesthesiology Research at St Michael's Hospital and the University of Toronto. D.N.W. has received honoraria from Edwards Lifesciences within the last 5 years and is a member of the Scientific Advisory Board for Surgical Safety Technologies Inc. T.E.F.A. is an NIHR Clinical Lecturer, an editor of the British Journal of Anaesthesia, has received research funding from the Medical Research Council, the National Institute of Academic Anaesthesia and Barts Charity, and has received consultancy fees from MSD and Edwards Life Sciences unrelated to this work. All other authors report no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years, and no other relationships or activities that could appear to have influenced the submitted work., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Delivering higher doses of protein to mechanically ventilated critically ill patients did not improve patient outcomes and may have caused harm. Longitudinal urea measurements could provide additional information about the treatment effect of higher protein doses. We hypothesised that higher urea values over time could explain the potential harmful treatment effects of higher doses of protein., Methods: We conducted a reanalysis of a randomised controlled trial of higher protein doses in critical illness (EFFORT Protein). We applied Bayesian joint models to estimate the strength of association of urea with 30-day survival and understand the treatment effect of higher protein doses., Results: Of the 1301 patients included in EFFORT Protein, 1277 were included in this analysis. There were 344 deaths at 30 days post-randomisation. By day 6, median urea was 2.1 mmol/L higher in the high protein group (95% CI 1.1-3.2), increasing to 3.0 mmol/L (95% CI 1.3-4.7) by day 12. A twofold rise in urea was associated with an increased risk of death at 30 days (hazard ratio 1.34, 95% credible interval 1.21-1.48), following adjustment of baseline characteristics including age, illness severity, renal replacement therapy, and presence of AKI. This association persisted over the duration of 30-day follow-up and in models adjusting for evolution of organ failure over time., Conclusions: The increased risk of death in patients randomised to a higher protein dose in the EFFORT Protein trial was estimated to be mediated by increased urea cycle activity, of which serum urea is a biological signature. Serum urea should be taken into consideration when initiating and continuing protein delivery in critically ill patients., Clinicaltrials: gov Identifier: NCT03160547 (2017-05-17)., (© 2024. The Author(s).)