Department of Anaesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany.
Institute of Biostatistics and Clinical Research, University of Münster, Münster, Germany.
Crit Care. 2023 Jul 10;27(1):276. doi: 10.1186/s13054-023-04556-w.
Recent evidence suggests an association of plasma Proenkephalin A 119-159 (penKid) with early and successful liberation from continuous renal replacement therapy (CRRT) in critically ill patients with acute kidney injury. However, these exploratory results are derived from a monocentric trial and therefore require external validation in a multicenter cohort.
Data and plasma samples from the "Effect of Regional Citrate Anticoagulation versus Systemic Heparin Anticoagulation During Continuous Kidney Replacement Therapy on Dialysis Filter Life Span and Mortality Among Critically Ill Patients With Acute Kidney Injury-A Randomized Clinical Trial" (RICH Trial) were used for this validation study. PenKid was measured in all plasma samples available at CRRT initiation and at day 3 of CRRT. Patients were categorized into low and high penKid groups with a cutoff at 100 pmol/l. Competing-risk time-to-event analyses were performed. Competing risk endpoints were successful and unsuccessful liberation from CRRT, the latter meaning death or initiation of a new RRT within one week of discontinuation of primary CRRT. Then penKid was compared to urinary output.
Low pre-CRRT penKid levels at CRRT initiation were not associated with early and successful liberation from CRRT compared to patients with high pre-CRRT penKid levels [subdistribution hazard ratio (sHR) 1.01, 95% CI 0.73-1.40, p = 0.945]. However, the landmark analysis on day 3 of ongoing CRRT demonstrated an association between low penKid levels and successful liberation from CRRT (sHR 2.35, 95% CI 1.45-3.81, p < 0.001) and an association between high penKid levels and unsuccessful liberation (sHR 0.46, 95% CI 0.26-0.80, p = 0.007). High daily urinary output (> 436 ml/d) was even stronger associated with successful liberation (sHR 2.91, 95% CI 1.80-4.73, p < 0.001) compared to penKid.
This study suggests that penKid may be a competent biomarker to monitor the recovery of kidney function during CRRT. This is in line with previous findings and investigated this concept in a multicenter cohort. Again, low penKid was associated with early and successful CRRT liberation, but was outperformed by high daily urinary output. The findings of this study now warrant further evaluation in prospective studies or a randomized controlled trial. Trial registration The RICH Trial was registered at clinicaltrials.gov: NCT02669589. Registered 01 February 2016.
最近的证据表明，血浆前脑啡肽 A 119-159（penKid）与危重病患者急性肾损伤中连续肾脏替代治疗（CRRT）的早期和成功脱离有关。然而，这些探索性结果来自于一项单中心试验，因此需要在多中心队列中进行外部验证。
本验证研究使用了“Effect of Regional Citrate Anticoagulation versus Systemic Heparin Anticoagulation During Continuous Kidney Replacement Therapy on Dialysis Filter Life Span and Mortality Among Critically Ill Patients With Acute Kidney Injury-A Randomized Clinical Trial”（RICH 试验）的数据和血浆样本。在 CRRT 开始时和 CRRT 第 3 天测量所有可用的血浆样本中的 penKid。将 penKid 分为低和高两组，截断值为 100 pmol/L。进行竞争风险时间事件分析。竞争风险终点是 CRRT 的成功和不成功的脱离，后者是指在停止主要 CRRT 后的一周内死亡或开始新的 RRT。然后将 penKid 与尿量进行比较。
与高预 CRRT penKid 水平的患者相比，CRRT 开始时低预 CRRT penKid 水平与早期和成功脱离 CRRT 无关[亚分布危险比（sHR）1.01，95%CI 0.73-1.40，p=0.945]。然而，正在进行的 CRRT 第 3 天的里程碑分析表明，低 penKid 水平与成功脱离 CRRT 之间存在关联（sHR 2.35，95%CI 1.45-3.81，p<0.001），高 penKid 水平与不成功脱离相关（sHR 0.46，95%CI 0.26-0.80，p=0.007）。与 penKid 相比，高每日尿量（>436ml/d）与成功脱离的相关性更强（sHR 2.91，95%CI 1.80-4.73，p<0.001）。
本研究表明，penKid 可能是监测 CRRT 期间肾功能恢复的一种有能力的生物标志物。这与之前的研究结果一致，并在多中心队列中对此概念进行了研究。同样，低 penKid 与早期和成功的 CRRT 脱离有关，但不如高每日尿量有效。本研究的结果现在需要在前瞻性研究或随机对照试验中进一步评估。试验注册 RICH 试验在 clinicaltrials.gov 上注册：NCT02669589。注册日期：2016 年 2 月 1 日。
