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| CONSENSUS |
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| Year : 2019 | Volume
: 1
| Issue : 2 | Page : 48-51 |
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Pragmatic Studies for Acute Kidney Injury in China: Renal Replacement Therapy for Acute Kidney Injury and Sepsis Consensus Report of Acute Disease Quality Initiative XIX
John R Prowle1, Bin Du2, Changsong Wang3, Martin Gallagher4
1 William Harvey Research Institute, Adult Critical Care Unit, Royal London Hospital, QueenMary University of London, London, UK
2 Department of MICU, Beijing Union Hospital, Beijing, China
3 Department of Critical Care Medicine, Harbin Medical University the Third Affiliated Hospital, Harbin, China
4 The George Institute for Global Health, Concord Clinical School, Sydney Medical School, NSW, Australia
| Date of Submission | 22-Aug-2018 |
| Date of Acceptance | 15-Mar-2019 |
| Date of Web Publication | 27-Sep-2019 |
Correspondence Address:
Dr. John R Prowle
William Harvey Research Institute, Queen Mary University of London, Adult Critical Care Unit, Royal London Hospital, Whitechapel Road, London E1 1BB
UK
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/jtccm.jtccm_12_18
In this article, we report consensus of 19th Acute Disease Quality Initiative (ADQI) conference and pragmatic trial proposals on renal replacement therapy (RRT) for acute kidney injury (AKI)and sepsis. The committee develop a list of key questions for the pragmatic trials. Then a systematic literature search was performed using PubMed and Embase. Finally the group summarized the proposed trials using PICO(Patient, Intervention, Comparator, Outcome). The groups recommended the first step would be a prospective observational study to document the current clinical practice of RRT in ICUs. Then the second stage would be to develop a quality improvement (QI) tools to improve and standardize the RRT practice in ICUs. The committee also proposed the primary outcome and secondary outcomes of the trial. Consensus had been reached for the pragmatic trial of RRT for AKI and sepsis in Chinese ICUs.
Keywords: Acute kidney injury, prospective observational study, renal replacement therapy, sepsis
How to cite this article:
Prowle JR, Du B, Wang C, Gallagher M. Pragmatic Studies for Acute Kidney Injury in China: Renal Replacement Therapy for Acute Kidney Injury and Sepsis Consensus Report of Acute Disease Quality Initiative XIX. J Transl Crit Care Med 2019;1:48-51 |
How to cite this URL:
Prowle JR, Du B, Wang C, Gallagher M. Pragmatic Studies for Acute Kidney Injury in China: Renal Replacement Therapy for Acute Kidney Injury and Sepsis Consensus Report of Acute Disease Quality Initiative XIX. J Transl Crit Care Med [serial online] 2019 [cited 2023 Mar 31];1:48-51. Available from: http://www.tccmjournal.com/text.asp?2019/1/2/48/268084 |
| Introduction | |  |
Little information is available about the disease burden of acute kidney injury (AKI) in Mainland China; however, it is undoubtedly sizable. A prospective, multicenter, cross-sectional survey of hospitalized adult patients has reported the prevalence of AKI at 1%–2%, corresponding to 1.4–2.9 million cases in 2013.[1] In the Intensive Care Unit (ICU), the prevalence of AKI has been reported to range from 32% to 51%, with hospital mortality of up to 46%.[2],[3],[4],[5] Available evidence suggested that 20% to 25% of patients with AKI in Chinese ICUs are treated with renal replacement therapy (RRT)[2],[3],[4],[5] almost exclusively with continuous modalities. Overall reported prevalence of AKI and associated risk of death and rates of RRT use are broadly comparable to those reported in North America and Europe. However, within China, there is a perception of lack of standardization of acute RRT provision with significant practice variation.
We considered potential for Chinese researchers to address research questions around the use of acute RRT in the ICU. There are numerous unanswered questions about the use of RRT during critical illness that is relevant both within China and internationally. Despite extensive research and numerous adequately powered randomized controlled trials (RCTs) in thousands of patients, optimal modality, timing, and dose of RRT remain controversial. The ongoing uncertainty with regard to the optimal modality relates to concerns such as the subsequent risk of chronic kidney disease,[6] along with identification of specific subgroups (e.g., patients with fluid overload) in which a specific modality may be favored.[7] In addition, the heterogeneity of patients, organizational and practical issues, along with the impact of variable prescription and execution [8] may have acted as unadjusted confounders and blurred evidence and conclusions. We considered the potential to address some of these questions in large China-based studies examining such major questions as RRT indications and timing. However, the design of complex studies examining specific aspects RRT implementation requires detailed knowledge about existing practice and current outcomes to establish feasibility, equipoise, cost, and sample size. At present, this detailed picture does not exist in China. However, short of an interventional study, a detailed description of the sheer large of RRT treatments provided in Chinese ICUs could provide very valuable information in its own right while also being an essential prerequisite for the appropriate design of future prospective studies. Furthermore, it was felt likely that information collection on RRT delivery across the nation would be likely to reveal significant practice variation in indications, prescription, and delivery of RRT making the design of an interventional study very difficult in the absence of a well-established current standard of care for comparison. Thus, the consensus of this group was that the current primary research opportunity in China is to the first document the quality of RRT delivery in Chinese ICUs and then investigate interventions to standardize and improve RRT delivery [Figure 1]. | Figure 1: Algorithmic intervention domain map. Reproduced with permission of the acute dialysis quality initiative
Click here to view |
| Methods | | |
Develop a list of key questions for pragmatic trials
The overall aim is to provide relevant and feasible studies for AKI in China and create robust evidence for critical care nephrology. Recommendations include what questions to be addressed using pragmatic trials and how these trials should be conducted. Pragmatic trials inform a clinical or policy decision by providing evidence for adoption of the intervention into real-world clinical practice.
It seems this group focused on the provision of RRT, and two contexts were mentioned (1) AKI and (2) sepsis either as a subset of AKI (septic AKI [S-AKI]) or possible the use of RRT as a sepsis treatment in the absence or other need for RRT.
Background information required
What was the epidemiology of AKI (and S-AKI) in the ICU in China and how and why was RRT currently employed. These would establish feasibility and equipoise for RCTs in China.
How to optimize using renal replacement therapy to improve outcomes in acute kidney injury?
Key areas for studies?
- RCT comparing early versus late RRT initiation with inclusion guided by biomarker (s) of nonrecovery
- RCT assessing the impact on renal outcome and health economics of using specific indicators for RRT discontinuation versus usual care
- RCT assessing the impact of a fluid removal strategy versus usual care on the development of AKI in patients with fluid overload
- Procedural aspects of RRT for AKI: catheter site, anticoagulation, drug dosing
- Do we want to tackle “conventional” questions of modality, dose, timing?
Any specific roles for – or differences in the use of – renal replacement therapy in the management of sepsis and septic acute kidney injury?
Key areas for studies?
- RRT in sepsis in the absence of conventional criteria for RRT
- The timing of RRT in S-AKI – earlier? later?
- Dose of RRT in S-AKI
- Modality of RRT in S-AKI
- Anticoagulation in S-AKI
- Antibiotic dosing in S-AKI.
Very important question – what endpoints?
Many options:
- Mortality
- Sequential Organ Failure Assessment score
- ICU/hospital length of stay
- Renal recovery (how defined, dialysis AKI criteria?)
- “MAKE” 30, 60, 90, 365, etc
- Renal function (with death or end-stage renal disease assigned glomerular filtration rate 0)
- Duration of RRT
- Quality of life
- Surrogates/biomarkers.
Perform a systematic literature search
Participants were required to perform their own literature search to find any additional articles. Search strategy and terms were specified, and participants were prepared to defend any exclusion criteria. In general, the trend was to be as broad and inclusive as possible.
Compile a bibliography
References (and accompanying pdf) were organized centrally such that redundancy was minimized. A “dropbox” folder was established to facilitating sharing of documents between group members.
Summarize proposed trials using “PICO”
Important but feasible questions were identified to be answers using pragmatic trials. Considered the research already conducted, its strengths and weaknesses, the problems that have not been addressed (but that should be), the realities of which studies would get done and which ones would not, and tried to develop a prioritized agenda of research topics and studies that would move your work group's area forward if they were funded and conducted.
| Results and Discussions | | |
Research Opportunity: document and improve the quality of continuous RRT (CRRT) delivery.
The faculty thus recommended that a prospective observational study to describe the current practice and practice variation in delivery of acute RRT in Chinese ICUs is an essential first step to any research efforts in this field. The faculty believes that data from such a study would serve as a benchmark for future studies of ICU-based RRT in Mainland China and would provide essential statistics for the design of interventional studies including expected outcome and correlations in outcomes within and between ICUs, sample size calculation. In addition to documenting local practice quality improvement (QI) tools could be designed to meet locally relevant needs. Design of a prospective observational study could be template on studies examining the epidemiology of AKI in the ICU and the use of RRT in its treatment that have been undertaken elsewhere in the world.[9] This would allow swift adoption of a relevant data collection protocol and would provide a ready international comparator for Chinese AKI epidemiology and clinical practice. It is essential that any study is comprehensive while avoiding overly onerous data collection. Potential primary data points of interest for such a study are outlined in [Table 1]. | Table 1: Prospective observational study of renal replacement therapy - practice data collection
Click here to view |
The second stage of this project would then be to prospectively evaluate a QI intervention to improve and standardize practice delivery of RRT across a group of Chinese ICUs. This intervention would take the form of a QI checklist covering the prescription and delivery of CRRT [Table 2]. It was agreed that intervention would not be prescriptive in suggesting specific targets (beyond referring to existing international guidelines) but would merely mandate that explicit choices were made by treating clinicians for important treatment-related variables including dose, fluid balance target, blood flow rate, modality, vascular access site, anticoagulation, monitoring, and might suggest an evaluation pathway to be used in response to premature filter loss. It was felt that a strategy of phased implementation of this intervention as a QI process would be acceptable to clinicians and patients allowing for a stepped-wedge cluster randomized trial design,[10] with the stepwise adoption of the policy intervention in random sequence across ICUs throughout the time course of the study. Such a design would avoid the requirement for patient-level consent as the study would constitute implementation clinically justifiable QI program, with collection of high-quality data to confirm the expected clinical effect. ICU level randomization was also regarded as essential to minimize cross-contamination of practice between study arms. The primary outcome of the proposed study would be to reveal an effect of the intervention on median filter lifespan during the first 72 h of treatment. While some participants questioned the relevance of this metric as a patient-centered clinical outcome, the overall consensus of the group was that filter lifespan represents a meaningful measure of well-delivered CRRT that would correlate with improved time on therapy, delivered dose as well as having important impact on cost of therapy, which might be particularly important in the Chinese environment, where patients and their families are often required to contribute a proportion of the direct costs of care. Based on this primary outcome, it is anticipated that randomization of 10–15 ICUs would enable a clinically meaningful benefit to be detected – with a formal power calculation dependent on baseline data on intra- and inter-cluster variation gathered in the prior observational study. Given the technical but pragmatic nature of the primary outcome, it was felt import to recommend a secondary assessment a more patient-centered clinical outcome acute kidney disease status at hospital discharge (a composite of patient survival and renal recovery). Finally, analysis of other secondary outcomes would be important as a process evaluation to better understand the effect mechanistic of the intervention on the study outcomes whether positive or negative. Design of a study would require careful evaluation of the current practice development and refining of the checklist intervention a process informed by prior observational data and involving a wide range of stakeholders in CRRT provision. | Table 2: Prospective assessment of a quality improvement intervention for prescription and delivery of continuous renal replacement therapy
Click here to view |
Overall, the group felt that a prospective observational study was an early achievable objective that would provide a wealth of data to understand and improve practice. The proposed intervention represents a form of research that has the potential to both improve practice and answer important questions regarding what constitutes quality RRT provision without the financial, ethical, and logistic burdens of a patient-level RCT examining a novel intervention. Importantly, this project would provide detailed baseline information, confidence in the conduct of collaborative clinical research, and a establish more level clinical playing field all of which being essential steps before more ambitious randomized studies examining specific aspects of RRT use could be successfully implemented.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Yang L, Xing G, Wang L, Wu Y, Li S, Xu G, et al. Acute kidney injury in China: A cross-sectional survey. Lancet 2015;386:1465-71.  |
| 2. | Wen Y, Jiang L, Xu Y, Qian CY, Li SS, Qin TH, et al. Prevalence, risk factors, clinical course, and outcome of acute kidney injury in Chinese Intensive Care Units: A prospective cohort study. Chin Med J (Engl) 2013;126:4409-16. |
| 3. | Zhou J, Yang L, Zhang K, Liu Y, Fu P. Risk factors for the prognosis of acute kidney injury under the acute kidney injury network definition: A retrospective, multicenter study in critically ill patients. Nephrology (Carlton) 2012;17:330-7. |
| 4. | Luo X, Jiang L, Du B, Wen Y, Wang M, Xi X, et al. A comparison of different diagnostic criteria of acute kidney injury in critically ill patients. Crit Care 2014;18:R144. |
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| 6. | Schneider AG, Bellomo R, Bagshaw SM, Glassford NJ, Lo S, Jun M, et al. Choice of renal replacement therapy modality and dialysis dependence after acute kidney injury: A systematic review and meta-analysis. Intensive Care Med 2013;39:987-97. |
| 7. | Truche AS, Darmon M, Bailly S, Clec'h C, Dupuis C, Misset B, et al. Continuous renal replacement therapy versus intermittent hemodialysis in intensive care patients: Impact on mortality and renal recovery. Intensive Care Med 2016;42:1408-17. |
| 8. | Schortgen F, Soubrier N, Delclaux C, Thuong M, Girou E, Brun-Buisson C, et al. Hemodynamic tolerance of intermittent hemodialysis in critically ill patients: Usefulness of practice guidelines. Am J Respir Crit Care Med 2000;162:197-202. |
| 9. | Hoste EA, Bagshaw SM, Bellomo R, Cely CM, Colman R, Cruz DN, et al. Epidemiology of acute kidney injury in critically ill patients: The multinational AKI-EPI study. Intensive Care Med 2015;41:1411-23. |
| 10. | Hemming K, Haines TP, Chilton PJ, Girling AJ, Lilford RJ. The stepped wedge cluster randomised trial: Rationale, design, analysis, and reporting. BMJ 2015;350:h391. |
[Figure 1]
[Table 1], [Table 2]
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