Custodero et al. conclude that N-terminal pro-brain natriuretic peptide (NT-proBNP) levels during the acute phase of sepsis may be a useful indicator of higher risk of long-term impairments in physical function and muscle strength in sepsis survivors [1]. A letter from Jiarong et al. has challenged this assertion, pointing to the exponential increase in the plasma level of NTproBNP with a declining glomerular filtration rate. As they have noted, it does not seem persuasive that NTproBNP could completely predict outcomes without adjusting for the covariate of renal function. They suggest that the relationship of NT-proBNP levels during the acute phase of sepsis and physical function and muscle strength outcomes in sepsis survivors be stratified based on the renal function [2]. In keeping with this, we would like to comment further. Nearly half of critically ill patients, especially with septic shock, have or develop acute kidney injury (AKI) and 20–25% need renal replacement therapy (RRT) within the first week of their stay [3]. In the Custodero study, the two cohorts (chronic critical illness [CCI] and rapid recovery [RAP]) had a considerable difference in the incidence of septic shock (36.5% vs 16.4%), so it would stand to reason that the rate of AKI and continuous renal replacement therapy (CRRT) was much lower in the RAP cohort when compared to the CCI cohort [1]. CRRT is performed using membranes that have a cut-off value of 35–40 kDa and therefore some quantity of NT-proBNP will be eliminated [4]. Because of its low molecular weight (8.5 kDa), NT-proBNP is likely to be effectively cleared by both highand low-flux membranes [4]. New highly adsorptive membranes (HAM) can adsorb many molecules with a molecular weight above 35 kDa and will increase this removal even further [4]. This could mislead patient prognostication by artificially decreasing NT-proBNP, but no studies have challenged this issue. Such studies should be done as there is already a long list of biomarkers in sepsis that are lacking reliability during CRRT [5]. As a consequence of the different rates of CRRT between the two cohorts, the reliability of NTproBNP to be a useful indicator of long-term impairments in physical function and muscle strength in sepsis survivors might be questioned.

中文翻译：

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脓毒症急性期的 N 端脑钠肽前体水平可能是长期损伤风险较高的有用指标：一些需要考虑的混杂因素

库斯托德罗等人。得出结论，脓毒症急性期的 N 端脑钠肽前体 (NT-proBNP) 水平可能是脓毒症幸存者身体功能和肌肉力量长期受损风险较高的有用指标 [1]。嘉荣等人的来信。对这一说法提出质疑，指出血浆 NTproBNP 水平呈指数增加，肾小球滤过率下降。正如他们所指出的，NTproBNP 可以在不调整肾功能协变量的情况下完全预测结果似乎没有说服力。他们建议根据肾功能对脓毒症急性期 NT-proBNP 水平与脓毒症幸存者的身体功能和肌肉力量结果之间的关系进行分层 [2]。为此，我们想进一步发表评论。近一半的危重患者，尤其是感染性休克患者，患有或发展为急性肾损伤 (AKI)，20-25% 的患者需要在住院第一周内接受肾脏替代治疗 (RRT) [3]。在 Custodero 研究中，两个队列（慢性危重病 [CCI] 和快速康复 [RAP]）在感染性休克的发生率方面存在相当大的差异（36.5% 对 16.4%），因此有理由认为与 CCI 队列相比，RAP 队列中的 AKI 和连续性肾脏替代治疗 (CRRT) 低得多 [1]。CRRT 使用截断值为 35-40 kDa 的膜进行，因此将消除一定量的 NT-proBNP [4]。由于其低分子量 (8.5 kDa)，NT-proBNP 很可能被高通量和低通量膜有效清除 [4]。新的高吸附膜 (HAM) 可以吸附许多分子量超过 35 kDa 的分子，并将进一步提高这种去除率 [4]。这可能会通过人为降低 NT-proBNP 来误导患者的预后，但没有研究对这个问题提出质疑。应该进行此类研究，因为在脓毒症中已经有一长串生物标志物在 CRRT 期间缺乏可靠性 [5]。由于两个队列的 CRRT 率不同，NTproBNP 作为脓毒症幸存者身体功能和肌肉力量长期损伤的有用指标的可靠性可能受到质疑。但没有研究挑战这个问题。应该进行此类研究，因为在脓毒症中已经有一长串生物标志物在 CRRT 期间缺乏可靠性 [5]。由于两个队列的 CRRT 率不同，NTproBNP 作为脓毒症幸存者身体功能和肌肉力量长期损伤的有用指标的可靠性可能受到质疑。但没有研究挑战这个问题。应该进行此类研究，因为在脓毒症中已经有一长串生物标志物在 CRRT 期间缺乏可靠性 [5]。由于两个队列的 CRRT 率不同，NTproBNP 作为脓毒症幸存者身体功能和肌肉力量长期损伤的有用指标的可靠性可能受到质疑。