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.
Am J Kidney Dis. 2015 May;65(5):748-53. doi: 10.1053/j.ajkd.2014.10.022. Epub 2014 Dec 17.
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).
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.
Dialysate appearance rates of MMP-2 and PAI-1.
EPS cases identified by 2 experienced nephrologists and a radiologist based on predefined criteria.
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.
Low event rate of EPS prevented independent validation in this single-center study.
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.
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。
诊断测试研究。
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。
MMP-2 和 PAI-1 的透液外观率。
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。
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。
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。
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。
