Human Proenkephalin A 119-159 (penKid) in Extracorporeal Therapies: Ex vivo Sieving Coefficient, Diffusive Clearance, and Hemoadsorption Kinetics.

IF 2.2 3区 医学 Q3 HEMATOLOGY Blood Purification 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
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Abstract

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.

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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。
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。
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来源期刊
Blood Purification
Blood Purification 医学-泌尿学与肾脏学
CiteScore
5.80
自引率
3.30%
发文量
69
审稿时长
6-12 weeks
期刊介绍: Practical information on hemodialysis, hemofiltration, peritoneal dialysis and apheresis is featured in this journal. Recognizing the critical importance of equipment and procedures, particular emphasis has been placed on reports, drawn from a wide range of fields, describing technical advances and improvements in methodology. Papers reflect the search for cost-effective solutions which increase not only patient survival but also patient comfort and disease improvement through prevention or correction of undesirable effects. Advances in vascular access and blood anticoagulation, problems associated with exposure of blood to foreign surfaces and acute-care nephrology, including continuous therapies, also receive attention. Nephrologists, internists, intensivists and hospital staff involved in dialysis, apheresis and immunoadsorption for acute and chronic solid organ failure will find this journal useful and informative. ''Blood Purification'' also serves as a platform for multidisciplinary experiences involving nephrologists, cardiologists and critical care physicians in order to expand the level of interaction between different disciplines and specialities.
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