黏蛋白可预测腹膜透析患者的基础腹膜转运特征，并减少腹膜蛋白丢失。

Orosomucoid can predict baseline peritoneal transport characteristics in peritoneal dialysis patients and reduce peritoneal proteins loss.

机构信息

Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Institute of Kidney Disease and Dialysis, Shanghai 200032, China; Shanghai Key Laboratory of Kidney Disease and Blood Purification, Shanghai 200032, China; Shanghai Medical Center of Kidney, Shanghai 200032, China.

Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.

出版信息

J Proteomics. 2021 Jun 30;242:104260. doi: 10.1016/j.jprot.2021.104260. Epub 2021 May 7.

DOI:10.1016/j.jprot.2021.104260

PMID:33965627

Abstract

Peritoneal dialysis (PD) is a replacement therapy for end-stage renal disease patients. In the first 4-8 weeks of PD, the patients were given an empirical dialysis prescription due to unknown peritoneal transport characteristics. Proteomic analysis could be used to identify serum biomarkers. In a discovery set, patients were divided into three groups according to the peritoneal equilibration test (PET) results: high (H), high average (HA), low average and low (LA&L) groups. A total of 1051 identified proteins were screened by Nano HPLC-MS/MS. The top two proteins among different peritoneal transport characteristics were Orosomucoid 2 (ORM2) and C-reactive protein (CRP). In a validation set, CRP was significantly elevated in H group than LA&L group, consistent with proteomic analysis. Serum ORM2 was enhanced in LA&L group compared with H and HA group. The expression of ORM2 in peritoneum was also enriched in LA&L group. At last, supplying exogenous ORM could reduce peritoneal proteins loss, without causing a pro-inflammatory response in mice. ORM2 and CRP could be used as biomarkers to predict the baseline peritoneal transport characteristics, and guide the early PD treatment. ORM may serve as a novel therapeutic target for decreasing peritoneal proteins loss in PD patients. SIGNIFICANCE: Peritoneal dialysis (PD) is associated with the functional alterations of the peritoneum. PD patients were often given an empirical dialysis prescription due to the unknown peritoneal transport characteristics in the first 4-8 weeks since PD started. Therefore, it is urgently needed to find biomarkers to predict the baseline peritoneal transport characteristics. In this study, we employed a proteomic analysis to identify serum biomarkers in a training set and verified the screened biomarkers in a validation set. We also found that Orosomucoid (ORM) has the potential to decrease peritoneal proteins loss in PD therapy.

摘要

腹膜透析（PD）是终末期肾病患者的替代治疗方法。在 PD 的最初 4-8 周内，由于未知的腹膜转运特性，患者接受经验性透析处方。蛋白质组学分析可用于识别血清生物标志物。在发现集中，根据腹膜平衡试验（PET）结果将患者分为三组：高（H）、高平均（HA）、低平均和低（LA&L）组。通过纳诺高效液相色谱-串联质谱法（Nano HPLC-MS/MS）筛选出 1051 种鉴定蛋白。不同腹膜转运特性的前两种蛋白是 Orosomucoid 2（ORM2）和 C-反应蛋白（CRP）。在验证集中，CRP 在 H 组中明显高于 LA&L 组，与蛋白质组学分析一致。LA&L 组血清 ORM2 水平高于 H 和 HA 组。LA&L 组腹膜 ORM2 的表达也更丰富。最后，外源性 ORM 的供给可以减少腹膜蛋白的丢失，而不会在小鼠中引起炎症反应。ORM2 和 CRP 可作为预测基线腹膜转运特性的生物标志物，并指导早期 PD 治疗。ORM 可能成为减少 PD 患者腹膜蛋白丢失的新治疗靶点。意义：腹膜透析（PD）与腹膜功能改变有关。PD 患者在开始 PD 的最初 4-8 周内，由于未知的腹膜转运特性，经常接受经验性透析处方。因此，迫切需要找到预测基线腹膜转运特性的生物标志物。在这项研究中，我们采用蛋白质组学分析在训练集中识别血清生物标志物，并在验证集中验证筛选出的生物标志物。我们还发现 Orosomucoid（ORM）有可能减少 PD 治疗中的腹膜蛋白丢失。