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包裹性腹膜硬化症中的腹腔渗出液 MMP-2 和 PAI-1。

Peritoneal effluent MMP-2 and PAI-1 in encapsulating peritoneal sclerosis.

机构信息

Division of Nephrology, Department of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam.

Division of Nephrology, Department of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam; Dianet Foundation, Amsterdam-Utrecht, the Netherlands.

出版信息

Am J Kidney Dis. 2015 May;65(5):748-53. doi: 10.1053/j.ajkd.2014.10.022. Epub 2014 Dec 17.

Abstract

BACKGROUND

Recently, the use of effluent matrix metalloproteinase 2 (MMP-2) and plasminogen activator inhibitor 1 (PAI-1) as potential biomarkers of peritoneal fibrosis has been demonstrated during longitudinal follow-up of incident peritoneal dialysis (PD) patients. This study focuses on effluent MMP-2 and PAI-1 as early diagnostic markers in the preceding years of patients who develop encapsulating peritoneal sclerosis (EPS).

STUDY DESIGN

Diagnostic test study.

SETTINGS & PARTICIPANTS: PD patients who developed EPS were compared with controls using a 1:3 case-control design with a minimum PD duration of 57 months.

INDEX TESTS

Dialysate appearance rates of MMP-2 and PAI-1.

REFERENCE TEST

EPS cases identified by 2 experienced nephrologists and a radiologist based on predefined criteria.

RESULTS

11 patients developed EPS within our center. The time course of MMP-2 appearance rates, studied by means of a linear repeated-measures model 4 years prior to the diagnosis of EPS, showed no difference between long-term controls and patients with EPS. In contrast, higher PAI-1 appearance rates were found in patients with EPS compared with controls (P=0.01). At a lag time of 1 year prior to EPS diagnosis, time-specific receiver operating characteristic curve analyses indicated a discriminative ability for PAI-1 appearance rate of 0.77 (95% CI, 0.63-0.91). A discriminative capacity was absent for those of MMP-2.

LIMITATIONS

Low event rate of EPS prevented independent validation in this single-center study.

CONCLUSIONS

Elevated levels of PAI-1 appearance rates are present in patients who develop EPS, pointing to progressive peritoneal fibrosis and sclerosis. The PAI-1 appearance rate has fair discriminative capacity from 3 years prior to EPS diagnosis. Therefore, effluent PAI-1 may aid in monitoring peritoneal fibrosis and serve as a biomarker for EPS.

摘要

背景

最近,在对新发生的腹膜透析(PD)患者进行纵向随访时,已经证明了废水中基质金属蛋白酶 2(MMP-2)和纤溶酶原激活物抑制剂 1(PAI-1)可作为潜在的腹膜纤维化生物标志物。本研究关注的是在发生包裹性腹膜硬化症(EPS)的患者的前几年中,作为早期诊断标志物的废水中 MMP-2 和 PAI-1。

研究设计

诊断测试研究。

设置和参与者

使用 1:3 的病例对照设计,将 PD 患者发展为 EPS 的患者与对照组进行比较,PD 持续时间至少为 57 个月。

索引测试

MMP-2 和 PAI-1 的透液外观率。

参考测试

根据预定义标准,由 2 名经验丰富的肾病学家和放射科医生确定的 EPS 病例。

结果

我们中心有 11 名患者发展为 EPS。通过线性重复测量模型研究,在诊断为 EPS 前 4 年,MMP-2 出现率的时间过程在长期对照组和 EPS 患者之间没有差异。相比之下,在 EPS 患者中发现 PAI-1 的出现率更高(P=0.01)。在诊断为 EPS 前 1 年的滞后时间,时间特异性接收者操作特征曲线分析表明 PAI-1 出现率具有 0.77(95%CI,0.63-0.91)的区分能力。对于 MMP-2 则不存在区分能力。

局限性

EPS 的低事件率使得在这项单中心研究中无法进行独立验证。

结论

发展为 EPS 的患者中 PAI-1 出现率升高,表明腹膜纤维化和硬化的进展。在诊断为 EPS 前 3 年,PAI-1 出现率具有良好的区分能力。因此,废水中的 PAI-1 可能有助于监测腹膜纤维化,并作为 EPS 的生物标志物。

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