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Relative Blood Volume Monitoring during Continuous Renal Replacement Therapy: A Prospective Observational Study. 连续性肾脏替代疗法 (CRRT) 期间的相对血容量监测:前瞻性观察研究
IF 2.2 3区 医学 Q3 HEMATOLOGY Pub Date : 2024-08-13 DOI: 10.1159/000540838
Akinori Maeda, Ian Baldwin, Sofia Spano, Anis Chaba, Atthaphong Phongphithakchai, Nuttapol Pattamin, Yukiko Hikasa, Rinaldo Bellomo, Emily See

Introduction: Hematocrit monitoring during continuous renal replacement therapy (CRRT) allows the continuous estimation of relative blood volume (RBV). This may enable early detection of intravascular volume depletion prior to clinical sequelae. We aimed to investigate the feasibility of extended RBV monitoring and its epidemiology during usual CRRT management by clinicians unaware of RBV. Moreover, we studied the association between changes in RBV and net ultrafiltration (NUF) rates.

Methods: In a cohort of adult intensive care unit patients receiving CRRT, we continuously monitored hematocrit and RBV using a pre-filter noninvasive optical sensor. We analyzed temporal changes in RBV and investigated the association between RBV change and NUF rates, using the classification of NUF rates into low, moderate, or high based on predefined cut-offs.

Results: We obtained >60,000 minute-by-minute measurements in >1,000 CRRT hours in 36 patients. The median RBV change was negative (decrease) in 69% of patients and the median peak change in RBV was -9.3% (interquartile range: -3.9% to -14.3%). Moreover, the median RBV decreased from baseline by >5% in 40.2% of measurements and by >10% in 20.6% of measurements. Finally, RBV decreased significantly more when patients received a high NUF rate (>1.75 mL/kg/h) compared to low or moderate NUF rates (5.32% vs. 1.93% or 1.97%, p < 0.001).

Conclusion: Continuous hematocrit and RBV monitoring during CRRT was feasible. RBV decreased significantly during CRRT, and decreases were greater with higher NUF rates. RBV monitoring may help optimize NUF management and prevent the occurrence of intravascular volume depletion.

简介在持续肾脏替代疗法(CRRT)期间进行血细胞比容监测可持续估算相对血容量(RBV)。这可以在出现临床后遗症之前及早发现血管内血容量耗竭。我们的目的是研究在不了解 RBV 的临床医生进行常规 CRRT 管理期间延长 RBV 监测的可行性及其流行病学。此外,我们还研究了 RBV 变化与净超滤率(NUF)之间的关联:在一组接受 CRRT 的成人重症监护室患者中,我们使用预滤器无创光学传感器连续监测血细胞比容和 RBV。我们分析了 RBV 的时间变化,并研究了 RBV 变化与 NUF 率之间的关联,根据预先确定的临界值将 NUF 率分为低、中、高三类:我们在 36 名患者的 1,000 个 CRRT 小时内进行了 60,000 次逐分钟测量。69%的患者中位 RBV 变化为负值(下降),中位 RBV 峰值变化为 -9.3%(IQR -3.9%-14.3%)。此外,在 40.2% 的测量中,RBV 的中位数比基线下降了 5%,在 20.6% 的测量中下降了 10%。最后,与低度或中度 NUF 率(5.32% vs 1.93% 或 1.97%,p<0.001)相比,当患者接受高 NUF 率(>1.75 ml/kg/h)时,RBV 下降幅度更大:结论:在 CRRT 期间连续监测血细胞比容和 RBV 是可行的。结论:在 CRRT 期间持续监测血细胞比容和 RBV 是可行的。RBV 监测有助于优化 NUF 管理,防止出现血管内容量耗竭。
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引用次数: 0
Coagulation Risk Predicting in Anticoagulant-Free Continuous Renal Replacement Therapy. 预测无抗凝剂 CRRT 的凝血风险。
IF 2.2 3区 医学 Q3 HEMATOLOGY Pub Date : 2024-08-12 DOI: 10.1159/000540695
Liang Liu, Dashuang Liu, Ting He, Bo Liang, Jinghong Zhao

Introduction: Continuous renal replacement therapy (CRRT) is a prolonged continuous extracorporeal blood purification therapy to replace impaired renal function. Typically, CRRT therapy requires routine anticoagulation, but for patients at risk of bleeding and with contraindications to sodium citrate, anticoagulant-free dialysis therapy is necessary. However, this approach increases the risk of CRRT circuit coagulation, leading to treatment interruption and increased resource consumption. In this study, we utilized artificial intelligence machine learning methods to predict the risk of CRRT circuit coagulation based on pre-CRRT treatment metrics.

Methods: We retrospectively analyzed 212 patients who underwent anticoagulant-free CRRT from October 2022 to October 2023. Patients were categorized into high-risk and low-risk groups based on CRRT circuit coagulation within 24 h. We employed eight machine learning methods to predict the risk of circuit coagulation. The performance of the model was evaluated using the area under the curve (AUC) of the receiver operating characteristic. 5-fold cross-validation was used to validate the machine learning models. Feature importance and SHAP plots were used to interpret the model's performance and key drivers.

Results: We identified 88 patients (41.51%) at high risk of circuit coagulation within 24 h of CRRT. Our machine learning models showed excellent predictive performance, with ensemble learning achieving an AUC of 0.863 (95% CI: 0.860-0.868), outperforming individual algorithms. Random forest was the best single-algorithm model, with an AUC of 0.819 (95% CI: 0.814-0.823). The top three features identified as most important by the SHAP summary plot and feature importance graph are platelet, filtration fraction (FF), and triglycerides.

Conclusion: We created a model using machine learning to predict the risk of circuit coagulation during anticoagulant-free CRRT therapy. Our model performs well (AUC 0.863) and identifies key factors like platelets, FF, and triglycerides. This facilitates the development of personalized treatment strategies by clinicians aimed at reducing circuit coagulation risk, thereby enhancing patient outcomes and reducing healthcare expenses.

简介连续性肾脏替代疗法(CRRT)是一种长期连续的体外血液净化疗法,用于替代受损的肾功能。通常情况下,CRRT 治疗需要常规抗凝,但对于有出血风险和对枸橼酸钠有禁忌症的患者来说,无抗凝剂透析治疗是必要的。然而,这种方法会增加 CRRT 回路凝血的风险,导致治疗中断和资源消耗增加。在这项研究中,我们利用人工智能机器学习方法,根据 CRRT 治疗前的指标预测 CRRT 循环凝血的风险:我们回顾性分析了 2022 年 10 月至 2023 年 10 月期间接受无抗凝剂 CRRT 的 212 例患者。根据 24 小时内 CRRT 循环凝血情况将患者分为高风险组和低风险组。我们采用了八种机器学习方法来预测回路凝血的风险。模型的性能使用接收者操作特征曲线下面积(AUC)进行评估。采用 5 倍交叉验证来验证机器学习模型。特征重要性图和SHAP图用于解释模型的性能和关键驱动因素:我们确定了 88 名患者(41.51%)在 CRRT 24 小时内存在回路凝血的高风险。我们的机器学习模型显示出卓越的预测性能,集合学习(EL)的AUC为0.863(95% CI 0.860 - 0.868),优于单个算法。随机森林(RF)是最好的单算法模型,AUC 为 0.819(95% CI 0.814 - 0.823)。SHAP汇总图和特征重要性图显示,最重要的前三个特征是血小板、FF和甘油三酯:我们利用机器学习创建了一个模型,用于预测无抗凝剂 CRRT 治疗期间发生回路凝血的风险。我们的模型表现良好(AUC 0.863),并能识别血小板、滤过分数和甘油三酯等关键因素。这有助于临床医生制定个性化的治疗策略,以降低回路凝血风险,从而提高患者预后并降低医疗费用。
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引用次数: 0
Haptoglobin Administration for Intravascular Hemolysis: A Systematic Review. 应用巯基乙醇治疗血管内溶血:系统回顾
IF 2.2 3区 医学 Q3 HEMATOLOGY Pub Date : 2024-08-05 DOI: 10.1159/000539363
Luca Baldetti, Rosa Labanca, Alessandro Belletti, André Dias-Frias, Beatrice Peveri, Yuki Kotani, Stefano Fresilli, Francesco Calvo, Evgeny Fominskiy, Marina Pieri, Silvia Ajello, Anna Mara Scandroglio

Introduction: Exogenous haptoglobin administration may enhance plasma-free hemoglobin (pfHb) clearance during hemolysis and reduce its end-organ damage: we systematically reviewed and summarized available evidence on the use of haptoglobin as a treatment for hemolysis of any cause.

Methods: We included studies describing haptoglobin administration as treatment or prevention of hemolysis-related complications. Only studies with a control group reporting at least one of the outcomes of interest were included in the quantitative synthesis. Primary outcome was the change in pfHb concentration 1 h after haptoglobin infusion.

Results: Among 573 articles, 13 studies were included in the review (677 patients, 52.8% received haptoglobin). Median initial haptoglobin intravenous bolus was 4,000 (2,000, 4,000) IU. Haptoglobin was associated with lower pfHb 1 h (SMD -11.28; 95% CI: -15.80 to -6.75; p < 0.001) and 24 h (SMD -2.65; 95% CI: -4.73 to -0.57; p = 0.001) after infusion. There was no difference in all-cause mortality between haptoglobin-treated patients and control group (OR 1.41; 95% CI: 0.49-4.95; p = 0.520). Haptoglobin was associated with a lower incidence of acute kidney injury (OR 0.64; 95% CI: 0.44-0.93; p = 0.020). No adverse events or side effects associated with haptoglobin use were reported.

Conclusions: Haptoglobin administration has been used in patients with hemolysis from any cause to treat or prevent hemolysis-associated adverse events. Haptoglobin may reduce levels of pfHb and preserve kidney function without increase in adverse events.

导言:外源性血红蛋白可提高溶血过程中无血浆血红蛋白(pfHb)的清除率,并减少其对终末器官的损害:我们试图系统地回顾和总结有关使用血红蛋白治疗任何原因引起的溶血的现有证据。方法 我们纳入了有关使用血红蛋白治疗或预防溶血相关并发症的研究。只有对照组报告了至少一种相关结果的研究才被纳入定量综述。主要结果是输注血红蛋白 1 小时后 pfHb 浓度的变化。结果 在 573 篇文章中,有 13 项研究被纳入综述(677 名患者,52.8% 接受了血红蛋白治疗)。初始血红蛋白静脉注射量的中位数为 4000(2000,4000)IU。血红蛋白与输注后 1 小时(SMD -11.28;95% CI -15.80~-6.75;p<0.001)和 24 小时(SMD -2.65;95% CI -4.73~-0.57;p=0.001)pfHb 的降低有关。经合血红蛋白治疗的患者与对照组的全因死亡率没有差异(OR 1.41;95% CI 0.49 至 4.95;P=0.520)。血红蛋白与较低的急性肾损伤发生率相关(OR 0.64;95% CI 0.44-0.93;P=0.020)。没有与使用隐血素相关的不良事件或副作用报道。结论 任何原因引起的溶血患者均可使用合血红蛋白治疗或预防与溶血相关的不良事件。合血红蛋白可降低 pfHb 水平,保护肾功能,同时不会增加不良反应。
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引用次数: 0
Retraction Statement. 勘误。
IF 3 3区 医学 Q1 Medicine Pub Date : 2024-02-12 DOI: 10.1159/000537697
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引用次数: 0
The Impact of Early Positive Studies on the Evolution of Extracorporeal Albumin Dialysis Literature: A Bibliometric Analysis. 早期实证研究对体外白蛋白透析文献演变的影响:文献计量分析。
IF 2.2 3区 医学 Q3 HEMATOLOGY Pub Date : 2024-01-01 Epub Date: 2023-10-31 DOI: 10.1159/000534915
Anis Chaba, Stephen Warrillow, Caleb Fisher, Akinori Maeda, Sofia Spano, Rinaldo Bellomo

Introduction: Liver failure is a life-threatening condition characterized by the accumulation of metabolic toxins. Extracorporeal albumin dialysis (ECAD) has been promoted as a possible therapy.

Methods: We employed bibliometric analysis to scrutinize the conceptual, intellectual, and social structure of the ECAD literature including its co-citation network and thematic analysis to explore its evolution and organization.

Results: We identified 784 documents with a mean of 30.25 citations per document in a corpus of 15,191 references. The average citation rate peaked in 1998 at 280.75 citations/year before a second 2013 peak of 54.81 citations/year and then progressively decreased to its nadir in 2022 (1.48 yearly citations). We identified four primary co-citation clusters, with the most impactful publications being small "positive" manuscripts by Mitzner et al. (2000) and Heemann et al. (2002) (Cluster 1). This first cluster had several relational citations with clusters 2 and 3, but almost no citation link with cluster 4 represented by Bañares et al. (2013), Saliba et al. (2013), and Larsen et al. (2016), with their three negative randomized controlled trials. Finally, the thematic map revealed a shift in focus over time, with inflammation and ammonia as recent emergent themes.

Conclusions: This bibliometric analysis provided a transparent and reproducible longitudinal assessment of ECAD literature and demonstrated how positive studies with low levels of evidence can dominate a research field and overshadow negative findings from higher quality studies. These insights hold significant implications for future research and clinical practice within this domain.

背景肝衰竭是一种以代谢毒素积累为特征的危及生命的疾病。体外白蛋白透析(ECAD)已被推广为一种可能的治疗方法。方法采用文献计量学分析方法,对ECAD文献的概念、智力和社会结构进行仔细研究,包括其共引网络和主题分析,以探索其演变和组织。结果在15191篇参考文献的语料库中,我们确定了784篇文献,平均每篇文献引用30.25次。平均引用率在1998年达到280.75次/年的峰值,2013年达到54.81次/年,然后在2022年逐渐降至最低点(1.48次/年)。我们确定了四个主要的共引集群,其中最具影响力的出版物是Mitzner等人(2000)和Heemann等人(2002)的小型“正面”手稿(集群1)。第一个聚类与聚类2和聚类3有几个相关引文,但与Banares等人代表的聚类4几乎没有引文联系。(2013)、Saliba等人(2013)和Larsen等人(2016),以及他们的三项阴性随机对照试验。最后,主题图显示了焦点随着时间的推移而发生的变化,炎症和氨是最近出现的主题。结论这一文献计量分析为ECAD文献提供了一个透明和可重复的纵向评估,并证明了低证据水平的阳性研究如何主导研究领域,并掩盖高质量研究的阴性结果。这些见解对该领域未来的研究和临床实践具有重要意义。
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引用次数: 0
"Renal": The First Forbidden Word in the Medical Lexicon. "肾脏":医学词典中的第一个禁词。
IF 2.2 3区 医学 Q3 HEMATOLOGY Pub Date : 2024-01-01 Epub Date: 2024-04-27 DOI: 10.1159/000536677
Rinaldo Bellomo, John A Kellum, Thiago Reis, Lui G Forni, Claudio Ronco
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引用次数: 0
Protein Kinase N1 Level Predicts Acute Kidney Injury in Patients Undergoing Cardiac Surgery: A Prospective Cohort Study. 预测心脏手术患者急性肾损伤的蛋白激酶 N1 水平:一项前瞻性队列研究。
IF 3 3区 医学 Q1 Medicine Pub Date : 2024-01-01 Epub Date: 2024-01-16 DOI: 10.1159/000536225
Lianjiu Su, Fangfang Zhu, Jiahao Zhang, Edward Z Cao, Cheng Yang, Haibing Sun, Xiaofang Jiang, Xiaozhan Wang, Jing Wang, Zhiyong Peng

Introduction: The objective of this study was to examine the utility of protein kinase N1 (PKN1) as a biomarker of cardiac surgery-associated AKI (CSA-AKI).

Methods: A prospective cohort study of 110 adults undergoing on-pump cardiac surgery was conducted. The associations between post-operative PKN1 and CSA-AKI, AKI severity, need for renal replacement therapy (RRT), duration of AKI, length of ICU stay, and post-operative hospital stay were evaluated.

Results: Patients were categorized into three groups according to PKN1 tertiles. The incidence of CSA-AKI in the third tertile was 3.4-fold higher than that in the first. PKN1 was an independent risk factor for CSA-AKI. The discrimination of PKN1 to CSA-AKI assessed by ROC curve indicated that the AUC was 0.70, and the best cutoff was 5.025 ng/mL. This group (>5.025 ng/mL) was more likely to develop CSA-AKI (p < 0.001). The combined AUC of EuroSCORE, aortic cross-clamp time, and PKN1 was 0.82 (p < 0.001). A higher level of PKN1 was related to increased need for RRT, longer duration of AKI, and length of ICU and post-operative hospital stays.

Conclusions: PKN1 could be a potential biomarker for the prediction of CSA-AKI. The combination of PKN1, EuroSCORE, and aortic cross-clamp time was likely to predict the occurrence of CSA-AKI.

简介本研究旨在探讨蛋白激酶 N1(PKN1)作为心脏手术相关性 AKI(CSA-AKI)生物标志物的效用:方法:对110名接受泵上心脏手术的成人进行了前瞻性队列研究。研究评估了术后 PKN1 与 CSA-AKI、AKI 严重程度、肾脏替代治疗(RRT)需求、AKI 持续时间、重症监护室住院时间和术后住院时间之间的关系:结果:根据PKN1三元组将患者分为三组。第三梯队的 CSA-AKI 发生率是第一梯队的 3.4 倍。PKN1是CSA-AKI的独立危险因素。用ROC曲线评估PKN1对CSA-AKI的区分度,结果显示AUC为0.70,最佳临界值为5.025ng/mL。该组(>5.025ng/mL)更有可能发展为 CSA-AKI(结论:PKN1 可能是一种潜在的生物指标:PKN1可能是预测CSA-AKI的潜在生物标志物。PKN1、EuroSCORE和主动脉瓣关闭时间的组合有可能预测CSA-AKI的发生。
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引用次数: 0
Seraph 100 Microbind Affinity Blood Filter Does Not Clear Antibiotics: An Analysis of Antibiotic Concentration Data from PURIFY-OBS. Seraph 100 微粘附亲和血液过滤器无法清除抗生素:PURIFY-OBS 抗生素浓度数据分析。
IF 3 3区 医学 Q1 Medicine Pub Date : 2024-01-01 Epub Date: 2024-01-13 DOI: 10.1159/000531951
Jesse P DeLuca, Daniel J Selig, Pooja Vir, Chau V Vuong, Jeffrey Della-Volpe, Ian M Rivera, Caroline Park, Benjamin Levi, Kathleen P Pratt, Ian J Stewart

Introduction: Novel hemoperfusion systems are emerging for the treatment of sepsis. These devices can directly remove pathogens, pathogen-associated molecular patterns, cytokines, and other inflammatory markers from circulation. However, significant safety concerns such as potential antibiotic clearance need to be addressed prior to these devices being used in large clinical studies.

Methods: Prospective, observational study of 34 participants undergoing treatment with the Seraph 100® Microbind Affinity Blood Filter (Seraph 100) device at 6 participating sites in the USA. Patients were included for analysis if they had a record of receiving an antibiotic concurrent with Seraph 100 treatment. Patients were excluded if there was missing information for blood flow rate. Blood samples were drawn pre- and post-filter at 1 h and 4 h after treatment initiation. These average pre- and post-filter time-concentration observations were then used to estimate antibiotic clearance in L/h (CLSeraph) due to the Seraph 100 device.

Results: Of the 34 participants in the study, 17 met inclusion and exclusion criteria for the antibiotic analysis. Data were obtained for 7 antibiotics (azithromycin, cefazolin, cefepime, ceftriaxone, linezolid, piperacillin, and vancomycin) and one beta-lactamase inhibitor. Mean CLSeraph for the antibiotics investigated ranged from -0.57 to 0.47 L/h. No antibiotic had a CLSeraph statistically significant from 0.

Discussion/conclusion: The Seraph 100 did not significantly clear any measured antibiotic in clinical samples. These data give further evidence to suggest that these therapies may be safely administered to critically ill patients and will not impact concentrations of administered antibiotics.

简介:用于治疗败血症的新型血液灌流系统不断涌现。这些设备可直接清除血液循环中的病原体、病原体相关分子模式、细胞因子和其他炎症标志物。然而,在将这些设备用于大型临床研究之前,需要解决潜在的抗生素清除等重大安全问题:前瞻性观察研究:在美国 6 个参与研究的机构对 34 名接受 Seraph 100® Microbind Affinity 血液过滤器(Seraph 100)治疗的患者进行观察。如果患者在接受赛拉弗 100 治疗的同时有接受抗生素治疗的记录,则纳入分析范围。如果血流量信息缺失,则排除患者。在开始治疗后一小时和四小时分别抽取过滤前和过滤后的血液样本。然后,利用这些过滤器前后的平均时间浓度观测值来估算瑟拉弗 100 设备的抗生素清除率,单位为升/小时(CLSeraph):在 34 位参与研究的人员中,有 17 位符合抗生素分析的纳入和排除标准。获得了 7 种抗生素(阿奇霉素、头孢唑啉、头孢吡肟、头孢曲松、利奈唑胺、哌拉西林和万古霉素)和 1 种β-内酰胺酶抑制剂的数据。所研究抗生素的平均 CLSeraph 值介于 -0.57 至 0.47 升/小时之间。没有一种抗生素的 CLSeraph 在统计学上显著低于 0.0:Seraph 100 不能明显清除临床样本中的任何抗生素。这些数据进一步证明,危重病人可以安全地使用这些疗法,而且不会影响抗生素的浓度。
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引用次数: 0
Efficacy of Therapeutic Apheresis for Cryoglobulinemic Vasculitis Patients with Renal Involvement: A Systematic Review. 单采治疗肾受累的冷球蛋白血症血管炎患者的疗效:系统评价。
IF 3 3区 医学 Q1 Medicine Pub Date : 2024-01-01 Epub Date: 2023-10-18 DOI: 10.1159/000534102
Jing Miao, Pajaree Krisanapan, Supawit Tangpanithandee, Charat Thongprayoon, Wisit Cheungpasitporn

Introduction: Therapeutic apheresis (TA) is commonly used for cryoglobulinemic vasculitis (CV) patients, but its efficacy remains uncertain. This systematic review aimed to assess the efficacy of different TA modalities, such as plasma exchange (PE), plasmapheresis (PP), and cryofiltration (CF), in treating CV patients with renal involvement.

Methods: Literature search of MEDLINE, EMBASE, and Cochrane Databases was conducted up to December 2022. Studies that reported the outcomes of TA in adult CV patients with renal involvement were assessed. The protocol for this systematic review has been registered with PROSPERO (No. CRD42023417727). The quality of each study was evaluated by the investigators using the validated methodological index for non-randomized studies (minors) quality score.

Results: 154 patients who encountered 170 episodes of serious events necessitating TA were evaluated across 76 studies. Among them, 51% were males, with a mean age ranging from 49 to 58 years. The CV types included 15 type I, 97 type II, and 13 type III, while the remaining patients exhibited mixed (n = 17) or undetermined CV types (n = 12). Among the treatment modalities, PE, PP, and CF were performed in 85 (56%), 52 (34%), and 17 patients (11%), respectively, with no identical protocol for TA treatment. The overall response rate for TA was 78%, with response rates of 84%, 77%, and 75% observed in type I, II, and III patients respectively. Most patients received steroids, immunosuppressants, and treatment targeting the underlying causative disease. The overall long-term renal outcome rate was 77%, with type I, II, and III patients experiencing response rates of 89%, 76%, and 90%, respectively. The renal outcomes in patients receiving PE, PP, and CF were comparable, with rates of 78%, 76%, and 81%, respectively.

Conclusions: This study presents compelling evidence that combination of TA with other treatments, especially immunosuppressive therapy, is a successful strategy for effectively managing severe renal involvement in CV patients. Among the TA modalities studied, including PE, PP, and CF, all demonstrated efficacy, with PE being the most frequently employed approach.

引言:治疗性单采(TA)通常用于冷球蛋白血症血管炎(CV)患者,但其疗效尚不确定。这项系统综述旨在评估不同TA模式,如血浆置换(PE)、血浆置换(PP)和冷冻过滤(CF),在治疗肾脏受累的CV患者中的疗效。方法:截至2022年12月,对MEDLINE、EMBASE和Cochrane数据库进行文献检索。对报告肾功能损害的成年CV患者TA结果的研究进行了评估。该系统审查的方案已在PROSPERO注册(编号CRD42023417727)。每项研究的质量由研究人员使用非随机研究(未成年人)质量评分的验证方法指数进行评估。结果:在76项研究中对154名患者进行了评估,他们遇到了170次需要TA的严重事件。其中,51%为男性,平均年龄在49至58岁之间。CV类型包括15种I型、97种II型和13种III型,而其余患者表现出混合型(n=17)或未确定的CV类型(n=12)。在治疗方式中,PE、PP和CF分别在85名(56%)、52名(34%)和17名(11%)患者中进行,TA治疗方案不相同。TA的总有效率为78%,在I型、II型和III型患者中观察到的有效率分别为84%、77%和75%。大多数患者接受了类固醇、免疫抑制剂和针对潜在病因的治疗。总的长期肾脏转归率为77%,I型、II型和III型患者的有效率分别为89%、76%和90%。接受PE、PP和CF治疗的患者的肾脏结果具有可比性,其发生率分别为78%、76%和81%。结论:本研究提供了令人信服的证据,证明TA与其他治疗,特别是免疫抑制治疗相结合,是有效管理CV患者严重肾脏受累的成功策略。在所研究的TA模式中,包括PE、PP和CF,均显示出疗效,PE是最常用的方法。
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引用次数: 0
Human Proenkephalin A 119-159 (penKid) in Extracorporeal Therapies: Ex vivo Sieving Coefficient, Diffusive Clearance, and Hemoadsorption Kinetics. 体外疗法中的人原脑啡肽 A 119-159 (PenKid):体外筛分系数、扩散清除率和血液吸收动力学。
IF 2.2 3区 医学 Q3 HEMATOLOGY Pub Date : 2024-01-01 Epub Date: 2024-07-26 DOI: 10.1159/000540061
Anna Lorenzin, Massimo de Cal, Natascha Perin, Niccolò Morisi, Alessandra Brendolan, Paolo Lentini, Monica Zanella, Claudio Ronco

Introduction: Enkephalins, endogenous opioid peptides, are involved in the regulation of renal function. One derived molecule, proenkephalin A, also known as penKid, has been demonstrated to be a reliable biomarker for kidney function and its plasma concentration correlates with measured glomerular filtration rate. penKid is used for prediction and diagnosis of AKI and need of renal replacement therapy (RRT). penKid has also been used to predict the successful weaning from RRT in patients with AKI. Whether the concentration of penKid is affected or not by RRT is a controversial point and there are no studies describing the kinetics of the molecule in such conditions. The low molecular weight (4.5 kDa) would imply free removal by the glomerulus and the dialysis membranes. During RRT, this reduction could not be detected in clinical practice due to the complex kinetics involving either low dialytic clearance or increased production in response to impaired kidney function. The aim of this study was to determine the sieving coefficient and the diffusive clearance of the penKid molecule in conditions of in vitro continuous veno-venous hemofiltration (CVVH) and continuous veno-venous hemodialysis (CVVHD), respectively, and also the penKid removal ratio in conditions of in vitro hemoadsorption (HA) using a synthetic microporous resin.

Methods: Blood spiked with a lyophilized penKid peptide solved in 20 mm dipotassium phosphate and 6 mm disodium EDTA [pH 8] to reach target concentrations is used as testing solution. In each experiment, the blood batch was adjusted at a volume of 1,000 mL, maintained at 37°, and continuously stirred. Samples were collected from blood, ultrafiltrate, and spent dialysate at different times during the experiments. Sieving, clearance, and removal ratio were calculated.

Results: Significant removal of penKid was observed in CVVH (sieving 1.04 ± 0.27), in CVVHD (clearance 23.08 ± 0.89), and in HA (removal ratio 76.1 ± 1% after 120 min).

Conclusion: penKid is effectively removed by extracorporeal therapies. In presence of anuria, penKid generation kinetics can be calculated based on extracorporeal removal and volume variation. In steady state conditions, declining values may be the result of an initial renal function recovery and may suggest discontinuation and successful liberation from RRT.

脑啡肽参与肾功能的调节。前叶脑啡肽 A(又称 PenKid)已被证明是肾功能的可靠生物标志物,其血浆浓度与测量的肾小球滤过率相关。PenKid 可用于预测和诊断 AKI 以及肾脏替代疗法(RRT)的需求。PenKid 还可用于预测 AKI 患者 RRT 的成功断流。PenKid 的浓度是否会受到 RRT 的影响是一个有争议的问题,目前还没有关于该分子动力学的研究。低分子量(4.5 kDa)意味着可被肾小球和透析膜自由清除。在 RRT 期间,由于透析清除率低或肾功能受损导致生成量增加等复杂的动力学原因,无法检测到这种减少。本研究的目的是分别测定体外连续静脉-静脉血液滤过(CVVH)和连续静脉-静脉血液透析(CVVHD)条件下 Penkid 的筛分系数和扩散清除率,以及使用合成微孔树脂进行体外血液吸附(HA)条件下 Penkid 的清除率。在每次实验中,血液批量调整为 1000 mL,保持在 37°并搅拌;血液中添加冻干的 PenKid 肽。在不同时间收集血液、超滤液和流出物样品。计算筛分率、清除率和去除率。在 CVVH(筛分率为 1.04±0.27)、CVVHD(清除率为 23.08±0.89)和 HA(120 分钟后清除率为 76.1±1%)中观察到 PenKid 被显著清除。体外疗法可有效清除 PenKid。在出现无尿的情况下,PenKid 的生成动力学可根据体外清除和容量变化进行计算。在稳态条件下,数值的下降可能是肾功能初步恢复的结果,也可能暗示着 RRT 的停止和成功解脱。
{"title":"Human Proenkephalin A 119-159 (penKid) in Extracorporeal Therapies: Ex vivo Sieving Coefficient, Diffusive Clearance, and Hemoadsorption Kinetics.","authors":"Anna Lorenzin, Massimo de Cal, Natascha Perin, Niccolò Morisi, Alessandra Brendolan, Paolo Lentini, Monica Zanella, Claudio Ronco","doi":"10.1159/000540061","DOIUrl":"10.1159/000540061","url":null,"abstract":"<p><strong>Introduction: </strong>Enkephalins, endogenous opioid peptides, are involved in the regulation of renal function. One derived molecule, proenkephalin A, also known as penKid, has been demonstrated to be a reliable biomarker for kidney function and its plasma concentration correlates with measured glomerular filtration rate. penKid is used for prediction and diagnosis of AKI and need of renal replacement therapy (RRT). penKid has also been used to predict the successful weaning from RRT in patients with AKI. Whether the concentration of penKid is affected or not by RRT is a controversial point and there are no studies describing the kinetics of the molecule in such conditions. The low molecular weight (4.5 kDa) would imply free removal by the glomerulus and the dialysis membranes. During RRT, this reduction could not be detected in clinical practice due to the complex kinetics involving either low dialytic clearance or increased production in response to impaired kidney function. The aim of this study was to determine the sieving coefficient and the diffusive clearance of the penKid molecule in conditions of in vitro continuous veno-venous hemofiltration (CVVH) and continuous veno-venous hemodialysis (CVVHD), respectively, and also the penKid removal ratio in conditions of in vitro hemoadsorption (HA) using a synthetic microporous resin.</p><p><strong>Methods: </strong>Blood spiked with a lyophilized penKid peptide solved in 20 m<sc>m</sc> dipotassium phosphate and 6 m<sc>m</sc> disodium EDTA [pH 8] to reach target concentrations is used as testing solution. In each experiment, the blood batch was adjusted at a volume of 1,000 mL, maintained at 37°, and continuously stirred. Samples were collected from blood, ultrafiltrate, and spent dialysate at different times during the experiments. Sieving, clearance, and removal ratio were calculated.</p><p><strong>Results: </strong>Significant removal of penKid was observed in CVVH (sieving 1.04 ± 0.27), in CVVHD (clearance 23.08 ± 0.89), and in HA (removal ratio 76.1 ± 1% after 120 min).</p><p><strong>Conclusion: </strong>penKid is effectively removed by extracorporeal therapies. In presence of anuria, penKid generation kinetics can be calculated based on extracorporeal removal and volume variation. In steady state conditions, declining values may be the result of an initial renal function recovery and may suggest discontinuation and successful liberation from RRT.</p>","PeriodicalId":8953,"journal":{"name":"Blood Purification","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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Blood Purification
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