AbstractOptimal strategy for volume control and the clinical implication of achieved volume control are unknown in patients with sepsis-associated acute kidney injury (AKI) receiving continuous renal replacement therapy (CRRT). This randomized controlled trial aimed to compare the survival according to conventional or bioelectrical impedance analysis (BIA)-guided volume control strategy in patients with sepsis-associated AKI receiving CRRT.

摘要接受连续性肾脏替代治疗（CRRT）的脓毒症相关急性肾损伤（AKI）患者的最佳容量控制策略和实现容量控制的临床意义尚不清楚。这项随机对照试验旨在比较接受CRRT的脓毒症相关AKI患者根据常规或生物电阻抗分析（BIA）指导的容量控制策略的生存率。

We also compared patient survival according to achieved volume accumulation rate ([cumulative fluid balance during 3 days × 100]/fluid overload measured by BIA at enrollment) as a post-hoc analysis. We randomly assigned patients to conventional volume control strategy (n = 39) or to BIA-guided volume control strategy (n = 34).

我们还根据达到的体积累积率（登记时BIA测量的3天内累积液体平衡/液体超负荷）比较了患者的生存率，作为事后分析。我们将患者随机分配到常规容量控制策略（n=39）或BIA引导的容量控制策略（n=34）。

There were no differences in 28-day mortality (HR, 1.19; 95% CI, 0.63–2.23) or 90-day mortality (HR, 0.99; 95% CI 0.57–1.75) between conventional and BIA-guided volume control group. In the secondary analysis, achieved volume accumulation rate was significantly associated with patient survival. Compared with the achieved volume accumulation rate of ≤  − 50%, the HRs (95% CIs) for the risk of 90-day mortality were 1.21 (0.29–5.01), 0.55 (0.12–2.48), and 7.18 (1.58–32.51) in that of  − 50–0%, 1–50%, and > 50%, respectively.

常规和BIA引导的容量控制组之间的28天死亡率（HR，1.19；95%CI，0.63-2.23）或90天死亡率（HR，0.99；95%CI 0.57-1.75）没有差异。在二次分析中，达到的体积累积率与患者生存率显着相关。与达到的体积累积率为50%相比，90天死亡风险的HR（95%CI）分别为1.21（0.29-5.01），0.55（0.12-2.48）和7.18（1.58-32.51），分别为50-0%，1-50%和>50%。

Hence, BIA-guided volume control in patients with sepsis-associated AKI receiving CRRT did not improve patient outcomes. In the secondary analysis, achieved volume accumulation rate was associated with patient survival..

因此，接受CRRT的脓毒症相关AKI患者的BIA引导容量控制并没有改善患者的预后。在二次分析中，达到的体积累积率与患者生存率相关。。

Acute kidney injury (AKI) is a common and serious complication among critically ill patients in intensive care units (ICUs)1,2,3. The mortality of those critically ill patients with AKI has been reported to reach approximately 60–80%3,4,5. Sepsis is the most common cause of AKI in patients treated in ICUs6,7,8,9.

急性肾损伤（AKI）是重症监护病房（ICU）危重患者常见且严重的并发症1,2,3。据报道，AKI重症患者的死亡率约为60-80%3,4,5。脓毒症是ICUs6,7,8,9治疗患者AKI的最常见原因。

Patients with sepsis-associated AKI often require continuous renal replacement therapy (CRRT) and have a high risk of mortality10,11. Patients with sepsis-associated AKI receiving CRRT often experience fluid overload and recent studies have shown a relationship between fluid overload or cumulative fluid balance and adverse outcomes in critically ill patients12,13,14,15.Owing to the poor prognosis of patients with sepsis-associated AKI requiring CRRT, a number of studies have been conducted to find an optimal strategy for prescribing CRRT, including the timing of the initiation and dosing of kidney support16,17,18,19,20,21,22,23.

脓毒症相关AKI患者通常需要连续性肾脏替代治疗（CRRT），死亡率高10,11。接受CRRT的脓毒症相关AKI患者经常会出现液体超负荷，最近的研究表明，危重患者的液体超负荷或累积液体平衡与不良结局之间存在关系[12,13,14,15]。由于脓毒症相关AKI患者的预后不良需要CRRT，已经进行了许多研究，以找到处方CRRT的最佳策略，包括肾脏支持的开始和给药时间[16,17,18,19,20,21,22,23]。

However, clinical trials designed to evaluate the optimal approach to guide fluid removal using CRRT in these patients are still lacking. Additionally, information on the association between the resolution of fluid overload and clinical outcomes is relatively scarce.Accurate volume status evaluation is essential for the appropriate management of patients with excessive body fluid receiving CRRT.

然而，仍然缺乏旨在评估在这些患者中使用CRRT指导液体清除的最佳方法的临床试验。。准确的容量状态评估对于正确管理接受CRRT的体液过多患者至关重要。

Conventionally, a review of daily fluid balance, physical examination, and chest radiography are used to estimate the amount of excess fluid in critically ill patients with AKI. However, these approaches are considered inaccurate24,25,26. Bioelectrical impedance analysis (BIA) is a simple and relatively reliable method for estimating the body composition, particularly for detecting fluid overload27,28,29.

通常，对每日液体平衡，体格检查和胸部X线照相的回顾用于估计AKI危重患者的过量液体量。然而，这些方法被认为是不准确的24,25,26。生物电阻抗分析（BIA）是一种简单且相对可靠的估计身体成分的方法，特别是用于检测液体超负荷27,28,29。

However, the effect of BIA on the manage.

然而，BIA对管理层的影响。

Table 1 Baseline characteristics and the risk of outcomes according to volume control strategies.Full size tableVolume reduction, fluid balance and CRRT prescription status according to volume control strategiesTable 2 shows volume reduction, fluid balance, and CRRT prescription status. The BIA-guided volume control strategy achieved target daily volume reduction in 21.7–26.5% of subjects, whereas the conventional volume control strategy reduced one-third of overhydration in 9.4–13.5% of subjects daily.

表1根据容量控制策略的基线特征和结果风险。根据容量控制策略，全尺寸表容量减少，液体平衡和CRRT处方状态稳定2显示容量减少，液体平衡和CRRT处方状态。。

Over 3 days, patients allocated to the BIA-guided volume control strategy appeared to have a lower fluid balance than those allocated to the conventional volume control strategy. In contrast, the ultrafiltration volumes during the intervention period were 2,222 (SD, 796) mL/day with the conventional volume control strategy and 2,723 (SD, 1,114) mL/day with the BIA-guided volume control strategy (P-value 0.03).

。相比之下，干预期间的超滤量为2222（SD，796）mL/天，常规容量控制策略为2723（SD，1114）mL/天，BIA引导容量控制策略为2723（SD，1114）mL/天（P值0.03）。

Additionally, the ultrafiltration rates were 36.2 (SD: 13.7) mL/kg/day and 44.6 (SD: 19.5) mL/kg/day, respectively (P-value 0.04). The mean CRRT doses were 36.9 (SD, 3.7) mL/kg/h in the conventional volume control group and 38.5 (SD, 3.1) mL/kg/h in the BIA-guided volume control group, showing a marginal statistical difference (P-value 0.06)..

此外，超滤率分别为36.2（SD:13.7）mL/kg/天和44.6（SD:19.5）mL/kg/天（P值0.04）。常规容量对照组的平均CRRT剂量为36.9（SD，3.7）mL/kg/h，BIA引导的容量对照组为38.5（SD，3.1）mL/kg/h，显示出边际统计学差异（P值0.06）。。

Table 2 Volume control, fluid balance, and CRRT prescription status in the two treatment groups during the intervention.Full size tablePatient outcomes according to volume control strategiesOverall, 20 of the 39 (51.3%) patients in the conventional volume control group died within 28 days of randomization compared to 19 of the 34 patients (55.9%) in the BIA-guided volume control group.

表2干预期间两个治疗组的容量控制，液体平衡和CRRT处方状态。全尺寸表患者结果根据容量控制策略，常规容量控制组39例患者中有20例（51.3%）在随机分组后28天内死亡，而BIA引导的容量控制组34例患者中有19例（55.9%）死亡。

By day 90, 27 (69.2%) patients had died in the conventional volume control group compared with 22 (64.7%) in the BIA-guided volume control group (Table 1). Survival rates at 28 (P = 0.584) and 90 (P = 0.984) days after randomization did not differ significantly between the treatment groups (Fig. 1).

到第90天，常规容量控制组有27例（69.2%）患者死亡，而BIA引导的容量控制组有22例（64.7%）（表1）。。

Additionally, there was no difference in the rates of ICU and in-hospital deaths and 7-day mortality between the treatment groups (Table 1 and Supplementary Fig. S1).Figure 1Kaplan–Meier curves showing patient survival according to volume control strategies. Cumulative survival probability within (A) 28-day and (B) 90-day of continuous renal replacement therapy initiation according to volume control strategies.

此外，治疗组之间ICU和院内死亡率以及7天死亡率没有差异（表1和补充图S1）。图1Kaplan–Meier曲线显示了根据容量控制策略的患者生存率。根据容量控制策略，连续肾脏替代治疗开始后（A）28天和（B）90天内的累积生存概率。

Log-rank tests were used for comparison between groups. BIA bioelectrical impedance analysis.Full size imageIn a univariate Cox regression analysis, BIA-guided volume control dsid not significantly improve 28-day (HR, 1.19; 95% CI, 0.63–2.23; P = 0.591) nor 90-day (HR, 0.99; 95% CI 0.57–1.75; P = 0.984) survival.

对数秩检验用于组间比较。BIA生物电阻抗分析。全尺寸图像在单因素Cox回归分析中，BIA引导的容积控制dsid在28天（HR，1.19；95%CI，0.63-2.23；P=0.591）和90天（HR，0.99；95%CI 0.57-1.75；P=0.984）生存率方面没有显着改善。

In like manner, the BIA-guided volume control group did not show a difference in ICU death (HR, 1.20; 95% CI 0.62–2.22; P = 0.557), in-hospital death (HR, 0.99; 95% CI 0.57–1.73; P = 0.978), nor 7-day survival (HR, 1.19; 95% CI 0.50–2.86; P = 0.697) (Table 1).Additionally, we compared the VIS and VDI statuses according to volume control strategies.

同样，BIA引导的容量控制组在ICU死亡（HR，1.20；95%CI 0.62-2.22；P=0.557），院内死亡（HR，0.99；95%CI 0.57-1.73；P=0.978）和7天生存率（HR，1.19；95%CI 0.50-2.86；P=0.697）方面没有差异（表1）。此外，我们根据音量控制策略比较了VIS和VDI状态。

The VIS and VDI scores did no.

VIS和VDI分数没有。

Table 3 Clinical parameters tin the two treatment groups during the intervention.Full size tableBaseline characteristics according to achieved volume accumulation rate categoriesThe baseline characteristics of the 55 participants according to volume accumulation rate categories are presented in Supplementary Table S2.

表3干预期间两个治疗组的临床参数。根据达到的体积累积率类别的全尺寸表基线特征根据体积累积率类别，55名参与者的基线特征见补充表S2。

The overall demographic characteristics were similar to those in the primary analysis. Patients with high volume accumulation rates had higher VIS and VDI values, indicating hemodynamic instability. There were no differences in the APACHE II scores, SOFA scores, and various laboratory parameters.Patient outcomesA total of 26 (47.2%) and 35 (63.6%) deaths occurred within 28 days and 90 days of CRRT initiation, respectively (Supplementary Table S3).

总体人口统计学特征与初步分析相似。体积累积率高的患者的VIS和VDI值较高，表明血流动力学不稳定。APACHE II评分，SOFA评分和各种实验室参数没有差异。患者结果分别在CRRT开始后28天和90天内发生26例（47.2%）和35例（63.6%）死亡（补充表S3）。

ICU death and in-hospital death occurred in 27 (49.1%) and 39 (70.9%) patients, respectively. Patients with the highest achieved volume accumulation rate (> 50%) showed significantly higher rate of 28-day mortality (P < 0.001) and 90-day mortality (P < 0.001). Additionally, the rates of ICU death (P < 0.001) and in-hospital death (P < 0.001) were significantly higher in the group with the highest achieved volume accumulation rate (> 50%).Association of achieved volume accumulation rate with the patient survivalKaplan–Meier curves revealed that the cumulative 28- and 90-day survival probabilities were significantly lower for patients in the achieved volume accumulation range of > 50% than for the others (P < 0.001) (Supplementary Fig.

ICU死亡和院内死亡分别发生在27例（49.1%）和39例（70.9%）患者中。体积累积率最高（>50%）的患者28天死亡率（P<0.001）和90天死亡率（P<0.001）显着较高。此外，ICU死亡率（P<0.001）和院内死亡率（P<0.001）显着高于体积累积率最高（>50%）的组。达到的体积累积率与患者生存率的关联Kaplan-Meier曲线显示，达到体积累积范围>50%的患者的累积28天和90天生存概率显着低于其他患者（P<0.001）（补充图）。

S2).The association between the achieved volume accumulation rate and patient survival was further evaluated using multivariate Cox proportional hazard models. In the unadjusted model, the HRs (95% CIs) for the risk of 28- and 90-day mortality in the participants with the achieved vo.

S2）。使用多变量Cox比例风险模型进一步评估了达到的体积累积率与患者生存率之间的关联。在未经调整的模型中，达到vo的参与者的28天和90天死亡率风险的HR（95%CI）。

Data availability

数据可用性

The datasets generated during and/or analyzed in the current study are available from the corresponding author upon reasonable request.

在本研究期间产生和/或分析的数据集可根据合理要求从通讯作者处获得。

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Download referencesFundingThis work was supported by Fresenius Medical Care, Korea (ㅊ). The supporter did not have any role in study design; collection, analysis, and interpretation of data; writing the report; or the decision to submit the report for publication.Author informationAuthors and AffiliationsDepartment of Internal Medicine, Institute of Kidney Disease Research, Yonsei University College of Medicine, Seoul, Republic of KoreaCheol Ho Park, Hui-Yun Jung, Joohyung Ha, Hyung Woo Kim, Jung Tak Park, Seung Hyeok Han, Shin-Wook Kang & Tae-Hyun YooDepartment of Internal Medicine, International Saint Mary’s Hospital, Catholic Kwandong University, Incheon, Republic of KoreaHee Byung Koh & Jin Hyeog LeeAuthorsCheol Ho ParkView author publicationsYou can also search for this author in.

下载参考文献资助这项工作得到了韩国费森尤斯医疗保健公司的支持（ㅊ）。支持者在研究设计中没有任何作用；数据的收集，分析和解释；撰写报告；或决定将报告提交出版。作者信息作者和所属机构延世大学医学院肾脏疾病研究所内科，首尔，大韩民国何公园，许云荣，Joohyung Ha，Hyung Woo Kim，Jung Tak Park，Seung Hyeok Han，Shin Wook Kang＆Tae Hyun YooDepartment of International Saint Mary’s Hospital，天主教关东大学，仁川，KoreaHee Byung Koh＆Jin Hyeog LeeAuthorsCheol Ho ParkView作者出版物您也可以在中搜索这位作者。

PubMed Google ScholarHee Byung KohView author publicationsYou can also search for this author in

PubMed Google ScholarHee Byung KohView作者出版物您也可以在

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PubMed Google ScholarContributionsConceptualization: C.H.P, T.H.Y. Data curation: C.H.P, H.B.K, J.H.L, H.Y.J, J.H, T.H.Y. Formal analysis: C.H.P, H.B.K, T.H.Y. Investigation: C.H.P, T.H.Y. Methodology: C.H.P, H.W.K. Project administration: C.H.P, T.H.Y. Resources: C.H.P. Software: C.H.P.

PubMed谷歌学术贡献概念：C.H.P，T.H.Y.数据管理：C.H.P，H.B.K，J.H.L，H.Y.J，J.H，T.H.Y.形式分析：C.H.P，H.B.K，T.H.Y.调查：C.H.P，T.H.Y.方法：C.H.P，H.W.K.项目管理：C.H.P，T.H.Y.资源：C.H.P.软件：C.H.P。

Visualization: C.H.P, T.H.Y. Validation: C.H.P, T.H.Y. Supervision: J.T.P, S.H.H, S.W.K, T.H.Y. Funding acquisition: T.H.Y. Writing—original draft: C.H.P. Writing—review and editing: J.T.P, S.H.H, S.W.K, T.H.Y.Corresponding authorCorrespondence to.

。

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Tae Hyun Yoo。道德宣言

Competing interests

相互竞争的利益

Tae-Hyun Yoo reports research funding: Fresenius Medical Care, Korea. The other authors declared no competing interests. The opinions, results, and conclusions are those of the authors and are independent from this funding and data sources.

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Reprints and permissionsAbout this articleCite this articlePark, C.H., Koh, H.B., Lee, J.H. et al. Volume control strategy and patient survival in sepsis-associated acute kidney injury receiving continuous renal replacement therapy: a randomized controlled trial with secondary analysis.

转载和许可本文引用本文Park，C.H.，Koh，H.B.，Lee，J.H.等人。接受连续肾脏替代治疗的脓毒症相关急性肾损伤的容量控制策略和患者生存率：一项具有二次分析的随机对照试验。

Sci Rep 14, 14284 (2024). https://doi.org/10.1038/s41598-024-64224-zDownload citationReceived: 12 April 2024Accepted: 06 June 2024Published: 21 June 2024DOI: https://doi.org/10.1038/s41598-024-64224-zShare this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

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KeywordsBioelectrical impedance analysisContinuous renal replacement therapySepsis-associated acute kidney injuryVolume control

关键词生物电阻抗分析连续性肾脏替代治疗相关急性肾损伤体积控制

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