评估移植前肾脏质量的蛋白质生物标记物--现状与未来展望(综述)。

IF 5.7 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
International journal of molecular medicine Pub Date : 2024-12-01 Epub Date: 2024-09-27 DOI:10.3892/ijmm.2024.5431
Maksymilian Baryła, Michał Skrzycki, Roman Danielewicz, Maciej Kosieradzki, Marta Struga
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引用次数: 0

摘要

为了满足肾脏移植(KTx)的需求,不仅经常从标准标准捐献者(SCD;年龄在 60 岁以上的捐献者或年龄在 50 岁以上且具备以下两项条件的捐献者)那里获取器官:有高血压病史、血清肌酐水平≥1.5 mg/dl 或死于中风)。这样做的代价是原发性无功能(永久性高钾血症、高尿酸血症和体液超负荷,导致 KTx 后需要持续透析)、移植物功能延迟(KTx 后第一周内至少需要透析一次)、移植物较早脱落和泌尿系统并发症(膀胱输尿管反流、膀胱输尿管吻合口阻塞、漏尿)的风险较高。目前,还没有商业化的诊断工具可用于在 KTx 之前评估肾脏质量。目前可用的基于临床数据的预测模型(如肾脏捐献者档案指数)并不充分。一个很有前景的选择是应用灌注溶液检测肾脏质量的蛋白质生物标记物以及短期和长期结果的预测因子。然而,迄今为止,用 ELISA、Western 印迹法和细胞毒性检测法检测的蛋白质标志物尚未被确定为肾脏质量的有利预测指标。这些指标包括乳酸脱氢酶、谷胱甘肽 S-转移酶、脂肪酸结合蛋白、细胞外组蛋白、IL-18、中性粒细胞明胶酶相关脂褐素、MMPs 和肾损伤分子-1。不过,液相色谱-质谱(LC-MS)和芯片等新方法可以分析 KTx 前用于肾脏储存的无细胞保存液(包括作为肾脏储存方法之一的低温机器灌注)中悬浮/溶解的所有肾脏蛋白质,例如威斯康星大学的 Belzer。最近利用 LC-MS 进行的蛋白质组学研究发现,补体通路元件(C3、C1QB、C4BPA、C1S、C1R 和 C1RL)、去瘤蛋白、血液凝固通路元件和免疫球蛋白重变量 2-26 是预测移植前肾脏质量的新指标。这是因为研究发现它们与肾移植后 3 个月和 12 个月的估计肾小球滤过率相关。不过,还需要进一步开展蛋白质组学研究,重点研究从低体温和常温机器灌注中获得的不同标记物,以确认其预测价值并改进肾脏储存方法。因此,我们从 PubMed、Scopus、Embase 和 Web of Science 等网站上进行了文献综述,目的是总结目前最常研究的单个蛋白质生物标志物的相关知识。此外,还记录了有关保存过程中器官损伤的新型分析方法和见解,并讨论了在肾移植前评估器官质量的未来方向。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Protein biomarkers in assessing kidney quality before transplantation‑current status and future perspectives (Review).

To meet the demand for kidney transplants (KTx), organs are frequently retrieved not only from standard criteria donors (SCD; a donor who is aged <50 years and suffered brain death from any number of causes, such as traumatic injuries or a stroke) but also from expanded criteria donors (any donor aged >60 years or donors aged >50 years with two of the following: A history of high blood pressure, a creatinine serum level ≥1.5 mg/dl or death resulting from a stroke). This comes at the cost of a higher risk of primary non‑function (the permanent hyperkalemia, hyperuremia and fluid overload that result in the need for continuous dialysis after KTx), delayed graft function (the need for dialysis session at least once during the first week after KTx), earlier graft loss and urinary complications (vesico‑ureteral reflux, obstruction of the vesico‑ureteral anastomosis, urine leakage). At present, there are no commercially available diagnostic tools for assessing kidney quality prior to KTx. Currently available predictive models based on clinical data, such as the Kidney Donor Profile Index, are insufficient. One promising option is the application of perfusion solutions for protein biomarkers of kidney quality and predictors of short‑ and long‑term outcomes. However, to date, protein markers that can be detected with ELISA, western blotting and cytotoxic assays have not been identified to be a beneficial predictors of kidney quality. These include lactate dehydrogenases, glutathione S‑transferases, fatty acid binding proteins, extracellular histones, IL‑18, neutrophil gelatinase‑associated lipocalin, MMPs and kidney injury molecule‑1. However, novel methods, including liquid chromatography‑mass spectrometry (LC‑MS) and microarrays, allow the analysis of all renal proteins suspended/dissolved in the acellular preservation solution used for kidney storage before KTx (including hypothermic machine perfusion as one of kidney storage methods) e.g. Belzer University of Wisconsin. Recent proteomic studies utilizing LC‑MS have identified complement pathway elements (C3, C1QB, C4BPA, C1S, C1R and C1RL), desmoplakin, blood coagulation pathway elements and immunoglobulin heavy variable 2‑26 to be novel predictors of kidney quality before transplantation. This was because they were found to correlate with estimated glomerular filtration rate at 3 and 12 months after kidney transplantation. However, further proteomic studies focusing on distinct markers obtained from hypothermic and normothermic machine perfusion are needed to confirm their predictive value and to improve kidney storage methods. Therefore, the present literature review from PubMed, Scopus, Embase and Web of Science was performed with the aims of summarizing the current knowledge on the most frequently studied single protein biomarkers. In addition, novel analytical methods and insights into organ injury during preservation were documented, where future directions in assessing organ quality before kidney transplantation were also discussed.

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来源期刊
International journal of molecular medicine
International journal of molecular medicine 医学-医学:研究与实验
CiteScore
12.30
自引率
0.00%
发文量
124
审稿时长
3 months
期刊介绍: The main aim of Spandidos Publications is to facilitate scientific communication in a clear, concise and objective manner, while striving to provide prompt publication of original works of high quality. The journals largely concentrate on molecular and experimental medicine, oncology, clinical and experimental cancer treatment and biomedical research. All journals published by Spandidos Publications Ltd. maintain the highest standards of quality, and the members of their Editorial Boards are world-renowned scientists.
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