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通讯作者:

卢国元,E⁃mail:sdfyylgy@163.com

中图分类号:R692.5

文献标识码:A

文章编号:1007-4368(2021)11-1632-07

DOI:10.7655/NYDXBNS20211111

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参考文献 4
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参考文献 8
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参考文献 9
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参考文献 10
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参考文献 11
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参考文献 13
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参考文献 14
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参考文献 15
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参考文献 17
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参考文献 18
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参考文献 19
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参考文献 20
LIM P S,CHEN H P,CHEN C H,et al.Association be⁃ tween redox status of serum albumin and peritoneal membrane transport properties in patients on peritoneal dialysis[J].Blood Purif,2015,40(3):243-249
参考文献 21
ASANO M,ISHII T,HIRAYAMA A,et al.Differences in peritoneal solute transport rates in peritoneal dialysis[J].Clin Exp Nephrol,2019,23(1):122-134
参考文献 22
BERNARDO A P,CONTESSE S A,BAJO M A,et al.Peritoneal membrane phosphate transport status:a corner⁃ stone in phosphate handling in peritoneal dialysis[J].Clin J Am Soc Nephrol,2011,6(3):591-597
参考文献 23
NEURATH M F.IL⁃36 in chronic inflammation and cancer[J].Cytokine Growth Factor Rev,2020,55:70-79
目录contents

    摘要

    目的:探讨腹腔白介素(interleukin,IL)⁃36水平对腹膜透析患者腹膜溶质转运特性以及预后的预测价值。方法:收集2018年6月—2019年12月在苏州大学附属第一医院腹膜透析中心规律随访的111例持续不卧床腹膜透析患者(continuous ambulatory peritoneal dialysis,CAPD)过夜留腹的腹透流出液,并抽取静脉血。依据腹膜平衡试验(peritoneal equilibration test, PET)结果将患者分为高/高平均转运(H/HA)组以及低/低平均转运(L/LA)组。收集患者基本资料,随访17个月,记录随访患者不良事件。采用酶联免疫吸附测定(enzyme linked immunosorbent assay,ELISA)法检测患者腹透流出液以及血清中IL⁃36α、IL⁃ 36β、IL⁃36γ的水平。通过Pearson 相关分析、Logistic回归分析评价IL⁃36对腹膜溶质转运特性以及腹膜透析患者预后的预测价值。结果:CAPD患者中腹透流出液IL⁃36α、IL⁃36γ与PET试验中D/P Cr呈正相关(r =0.51,P <0.001;r =0.55,P <0.001),与D/ D0呈负相关(r =-0.40,P <0.001;r =-0.44,P <0.001)。IL⁃36α 呈现率(appearance rate,AR)及IL⁃36γ AR是腹膜转运特性的独立预测因素(OR=1.40,P =0.001;OR=1.08,P =0.016)。受试者工作特征曲线(receiver operating characteristic,ROC)曲线下面积 (area under curve,AUC)结果显示,IL⁃36α AR为0.75(95%CI:0.66~0.84),IL⁃36γ AR为0.79(95%CI:0.70~0.88)。腹透流出液IL ⁃36α AR也是CAPD患者不良事件发生的独立预测因素(OR=1.21,P =0.006),AUC为0.76(95%CI:0.64~0.89)。结论:CAPD患者中腹透流出液IL⁃36可能是预测腹膜溶质转运特性和患者预后的潜在生物学标志物。

    Abstract

    Objective:This study aims to evaluate the value of measurement of interleukin(IL)⁃36 in peritoneal dialysis effluent in predicting the peritoneal solute transport rate and prognosis in continuous ambulatory peritoneal dialysis(CAPD)patients. Methods: From June2018 to December 2019,a total of 111 CAPD patients in peritoneal dialysis center of the First Affiliated Hospital of Soochow University were analyzed,and overnight peritoneal effluents and peripheral blood were collected. The patients were grouped into H/HA or L/LA group according to the peritoneal equilibration test(PET)results,and the clinical data of the patients were collected. All the patients were followed up for 17 months,and adverse events were recorded. ELISA assays were used to assess IL ⁃ 36α,IL ⁃36β,and IL ⁃36γ levels in peritoneal effluents and serum. The predictive role of effluent IL ⁃ 36 was determined by Pearson correlation and logistic regression analysis. Results:The IL ⁃ 36α AR and IL ⁃ 36γ AR levels in overnight drained dialysate were significantly correlated with D/P Cr(r =0.51,P <0.001;r =0.55,P <0.001)and D/D0 glucose(r =- 0.40,P <0.001;r =- 0.44,P < 0.001). Logistical regression analysis showed that the effluent IL ⁃ 36α AR or IL ⁃ 36γ AR level in peritoneal effluents was an independent predictive factor for the peritoneal solute transport rate(OR=1.40,P =0.001;OR=1.08,P =0.016). The area under the receiver operating characteristic(ROC)curve of effluent IL⁃36α AR was 0.75(95%CI:0.66⁃0.84,P < 0.001);IL⁃36γ AR was 0.79(95%CI:0.70⁃0.88). Moreover,effluent IL⁃36α AR was also an independent predictive factor for the adverse events of CAPD patients (OR=1.21,P =0.006),and the ROC curve of IL⁃36α AR was 0.76(95%CI:0.64⁃0.89). Conclusion:Effluent IL⁃36 maybe a potential biomarker for predicting peritoneal solute transport rate and prognosis of CAPD patients.

  • 腹膜透析是终末期肾脏病患者(end⁃stage renal disease,ESRD)一种有效的肾脏替代治疗方式,并且其具有不受时间、地点限制的特点,中国腹膜透析人群的数量在近年呈爆发式增长[1-3]。但是随着透析时间的延长,腹膜溶质转运速率增高伴随腹膜超滤功能衰竭,是患者退出腹透的主要原因[4]。目前临床主要利用腹膜平衡试验(peritoneal equilibration test,PET)观察腹膜超滤及溶质转运评估腹膜功能,主要包括3个指标:4h腹透液与血液肌酐比值 (D/P Cr)、4h与0h腹透葡萄糖浓度比值(D/D0)以及4h超滤量,D/P Cr、D/D0与全因死亡率及住院率呈线性相关[5]。目前研究表明腹透患者长期的腹腔微炎症状态会导致腹膜结构和功能发生改变,是引起腹膜功能减退的重要因素,而腹膜局部能够产生炎症因子,包括白介素(interleukin,IL)⁃6、肿瘤坏死因子 (tumor necrosis factor,TNF)⁃α,可以反映腹膜溶质转运速率,可能是判断腹膜功能的生物标志物[6-7]

  • IL⁃1家族由各类单核细胞、上皮细胞、成纤维细胞产生,在调控生物体固有免疫应答中发挥重要作用,IL⁃36是IL⁃1家族的重要组成成分,包括IL⁃36α、 IL⁃36β、IL⁃36γ,其与特异性受体IL⁃36R结合后能够与IL⁃1R附属蛋白形成异源二聚体,激活下游炎症信号[8]。目前研究表明IL⁃36参与多种自身免疫性疾病,包括系统性红斑狼疮、多发性硬化、炎症性肠病等[9-10]。但是腹腔IL⁃36水平是否能够反映腹膜溶质转运功能尚未有报道。本研究通过检测腹透患者腹透流出液IL⁃36水平,与患者PET试验结果相比较,分析透出液IL⁃36水平与腹膜溶质转运特性的相关性,并对患者进行随访,旨在寻找反映腹膜功能的新的生物标志物。

  • 1 对象和方法

  • 1.1 对象

  • 2018年6月—2019年12月于苏州大学腹膜透析中心定期行PET试验评估的持续不卧床腹膜透析(continuous ambulatory peritoneal dialysis,CAPD) 的患者。排除标准:近6个月患有腹膜炎、受过腹部创伤或者其他急性炎症;近6个月有激素或免疫抑制剂使用史;患有结缔组织疾病、恶性肿瘤;临床资料不完整。最终,111例患者纳入了该项研究,所有受试者均签署知情同意书并经苏州大学附属第一医院医学伦理委员会批准。

  • 1.2 方法

  • 1.2.1 数据采集及随访

  • 收集入选患者的基本人口学资料,包括性别、年龄、是否患有糖尿病、是否患有高血压、是否患有心血管疾病(包括心力衰竭、急性心肌梗死、心律失常、心搏骤停、脑血管意外等)以及基础临床数据,包括血白蛋白、血磷、血钙、血红蛋白等,并收集随访17个月时死亡、转为血液透析、新发心血管疾病等资料。所有患者在行PET前1夜均行标准CAPD治疗,透析液留腹过夜,详细记录留腹时间及过夜流出液总量,次日早晨留取10mL腹透液以及静脉血,离心后置于-80℃冰箱保存。应用酶联免疫吸附测定(enzyme linked immunosorbent assay,ELISA) 的方法,按照试剂盒(R&D公司,美国)说明书检测透出液和外周血IL⁃36α、IL⁃36β、IL⁃36γ、IL⁃6的浓度,而细胞因子呈现率(appearance rate,AR)=腹透液细胞因子浓度(ng/mL)×透出液量(mL)/留腹时间 (min)。PET评估腹膜转运功能,并收集24h尿液和腹透液评估腹透充分性、尿素清除指数(Kt/V)。

  • 1.2.2 PET试验

  • 晨起后引出留置腹腔过夜的腹膜透析液(20min以上),随后在10min内以200mL/min的速度灌入2.5%葡萄糖腹透液2L(百特,钙浓度:1.25mmol/L),每灌入400mL变更体位,使腹透液充分混合,完毕后计时,使液体停留于腹腔4h,后利用20min排空腹腔内透析液,计量,并分别取0、2、4h的腹透液标本10min,并取灌入腹透液2h的外周血标本,在全自动生化检测仪(BECKMANC⁃OULTER DxC800)上检测肌酐及葡萄糖浓度,并采用美国密苏里大学实验室提供的校正因子(0.000 531 415)校正肌酐。患者依据PET结果进行分组,高转运组(D/P Cr=0.82~1.03,H组),高平均转运组(D/P Cr=0.65~0.81,HA组),低平均转运组(D/P Cr=0.50~0.64,LA组),低转运组(D/P Cr=0.34~0.49,L组)。由于高转运组和低转运组病例较少,本研究将上述患者分为H/HA和L/LA组。

  • 1.3 统计学方法

  • 应用SPSS21.0软件进行数据统计学处理,采用Kolmogorov⁃Smirnov检验法检验数据是否符合正态分布。符合正态分布的连续型变量的描述采用均数±标准差(x- ± s),不符合正态分布的连续型变量的描述采用中位数(四分位数)[MP 25P 75)],分类变量的描述采用百分比。正态分布的计量资料组间比较采用独立样本 t 检验或单因素方差分析,采用SNK法或Kruskall⁃Wallis法进行两两比较。非正态分布数据的组间比较使用非参数检验,分类变量的组间比较使用χ2 检验,变量间的相关性采用Pearson相关分析。应用多因素Logistic回归分析影响腹膜溶质转运特性(D/P Cr)或CAPD患者不良事件的预测因素,且各个协变量之间经方差膨胀因子(variance inflation factor,VIF)检测,无明显共线性。通过受试者工作特征曲线(receiver operating characteristic curve,ROC)及曲线下面积(area under curve, AUC)评价腹透液IL⁃36家族对于腹透溶质转运特性和不良事件的预测价值。所有检验均为双侧检验, P< 0.05为差异有统计学意义。

  • 2 结果

  • 2.1 一般资料

  • 111例CAPD患者中,男65例,女46例;70例属于H/HA组,41例属于L/LA组。L/LA组血清白蛋白、血红蛋白、D/D0、血磷、4h超滤量明显低于H/HA组;D/P Cr、腹透液IL⁃6AR明显高于H/HA组,差异具有统计学意义(P <0.05)。而两组在性别、年龄、腹透时间、高血压患病率、糖尿病患病率、心血管疾病患病率、血钙、甘油三酯、胆固醇、尿酸、肌酐、eGFR、甲状旁腺素上差异无统计学意义(表1)。

  • 表1 H/HA组和L/LA组临床特征及实验室结果

  • Table1 Clinical and laboratory parameters in H/HA group and L/LA group

  • 2.2 腹透流出液及血清中IL⁃36水平与PET试验结果的相关性分析

  • ELISA结果显示,腹透液中IL⁃36α AR为(7.66± 4.48)ng/min,IL⁃36β AR为(40.24±5.23)ng/min,IL⁃ 36γ AR为(37.41±15.72)ng/min;血清中IL ⁃36α为 (2.31±0.92)ng/mL,IL⁃36β 为(15.32±3.11)ng/mL,IL⁃ 36γ为(18.22±3.35)ng/mL。Pearson相关分析的结果显示,CAPD患者中腹透液IL⁃36αAR、IL⁃36γAR和PET试验中D/P Cr呈正相关(分别为r=0.51,P < 0.001;r=0.55,P <0.001),与D/D0呈负相关(分别为r=-0.40,P <0.001;r=-0.44,P <0.001),与4h超滤量无明显相关性。而血清中IL⁃36和PET结果无明显相关性(表2,图1)。

  • 2.3 腹透流出液中IL⁃36对腹膜转运特性的预测价值分析

  • 以腹膜透析溶质转运特性为因变量(H/HA和L/LA),建立未校正前,以及经H/HA和L/LA组间具有显著差异的IL⁃6AR、血清白蛋白、超滤量、血磷以及性别、年龄校正后的模型进行Logistic回归分析,结果显示IL⁃36α AR及IL⁃36γ AR是预测腹膜转运特性的预测因素(分别是OR=1.35,P <0.001;OR=1.07,P <0.001);而校正后,IL⁃36α AR及IL⁃36γ AR仍然是预测腹膜转运特性的独立预测因素(分别是OR=1.40,P=0.001;OR=1.08,P=0.016)。AUC结果显示,IL⁃36α AR为0.75(95%CI:0.66~0.84);IL⁃36γ AR为0.79(95%CI 0.70~0.88,图2)。

  • 表2 PET试验结果和腹透流出液或血清中IL⁃36的相关性分析

  • Table2 Correlation of the PET results and IL ⁃ 36in serum or peritoneal dialysis effluent

  • 图1 D/P Cr与腹透流出液IL⁃36α AR(A)及IL⁃36γ AR(B)的相关性分析

  • Fig.1 Correlation of D/P Cr and effluent IL⁃36α AR(A)or IL⁃36γ AR(B)

  • 2.4 IL⁃36对CAPD患者预后的预测价值分析

  • 随访17个月,将因超滤衰竭转为血液透析、出现新发心血管疾病、死亡定义为不良事件。111例患者中,3例死亡(H/HA组2例,L/LA组1例),7例因超滤衰竭转为血液透析(H/HA组6例,L/LA组1例), 12例出现新发心血管疾病(包括心力衰竭、急性心肌梗死、心律失常、心搏骤停、脑血管意外,其中H/HA组9例,L/LA组3例),利用Logistic回归模型分析建立未校正前,以及将性别、年龄、超滤量、透析时间、血白蛋白、血钙、血磷、Kt/V、是否患有高血压、是否患有糖尿病、是否患有心血管疾病、肌酐、甲状旁腺激素作为校正因素的模型,结果提示腹透流出液IL⁃ 36α AR是CAPD患者不良事件发生的预测因素(OR=1.28,95%CI:1.12~1.46,P=0.001),而经校正后,腹透流出液IL⁃36α AR仍然是CAPD患者不良事件发生的独立预测因素(OR=1.21,95%CI:1.06~1.39,P=0.006),AUC为0.76(95%CI:0.64~0.89,图3)。

  • 图2 腹透流出液IL⁃36α AR以及IL⁃36γ AR预测腹膜溶质转运特性的ROC曲线

  • Fig.2 ROC curve with effluent IL⁃36α AR or IL⁃36γ AR for prediction of peritoneal solute transport rate

  • 图3 腹透流出液IL⁃36AR预测腹膜透析患者不良事件的ROC曲线

  • Fig.3 ROC curve with effluent IL ⁃ 36AR for predic⁃ tion of adverse outcomes in peritoneal dialysis patients

  • 3 讨论

  • 目前我国有超过7万例ESRD患者接受腹膜透析为肾脏替代治疗方式,腹膜透析可以较大程度减轻对生活和工作的影响。但随着腹透时间的延长,腹膜出现结构异常(表现为腹膜纤维化、新生血管形成以及血管透明样变性),并出现腹膜溶质转运速率增高以及超滤衰竭[111-12]。一般认为因腹膜长期暴露于生物不相容的透析溶液、尿毒症毒素、高糖环境等因素下,腹腔中巨噬细胞、肥大细胞激活,分泌炎症因子,导致腹膜间皮细胞分泌促纤维化因子,如转化生长因子β1,导致大量伴有α平滑肌肌动蛋白、胶原形成的肌成纤维细胞在腹膜聚集,最终引起腹膜纤维化以及腹膜功能的丧失[13-16]。因此,慢性炎症状态可能是腹膜功能损伤的起始因素,多项研究已经表明腹膜间皮细胞分泌IL⁃6、基质金属蛋白酶等,表达水平随着透析时间的延长而增高,并且与腹膜溶质转运速率以及腹透的临床不良事件相关,提示相关炎症因子可能是反映腹腔慢性炎症状态及腹膜功能的良好指标[617]。而目前临床中普遍应用PET试验作为评估腹膜溶质转运类型的方式,但是该检测需要住院、过程相对繁琐,并耗费较长时间,因此寻求腹透液中可能的炎症因子作为生物标志物来预测腹膜功能,易于标本收集及检测,具有重要意义。

  • 本研究报道了在腹膜透析流出液中可以检测出IL⁃36,分析CAPD患者PET试验的结果,发现IL⁃ 36α、IL3⁃6γ与PET试验中D/P Cr呈正相关,与D/D0呈负相关,提示腹膜溶质转运速率增高的患者IL⁃ 36α、IL ⁃36γ升高;Logistic回归分析结果提示IL ⁃ 36α、IL⁃36γ是腹膜溶质转运特性的独立预测因素; 另外每例患者随访17个月,由于心血管事件往往与腹膜功能下降后液体负荷过重相关,并且是腹透患者死亡的主要原因[411],因此本研究将因超滤衰竭转为血液透析、新发心血管事件(心力衰竭、急性心肌梗死、心律失常、心搏骤停、脑血管意外)、死亡定义为不良事件,发生率为16.20%(H/HA组为24.29%,L/LA组为12.20%,χ2=2.34,P=0.15),Logistic回归分析发现校正混杂因素后,IL ⁃ 36α仍然是CAPD患者发生不良事件的独立预测因素。既往一项针对超过1万例CAPD患者PET试验的结果表明,D/P Cr与D/D0高度相关,并且是住院率及全因死亡率的独立预测因素,而4h超滤量与D/P Cr仅仅是弱相关,并且与住院率及全因死亡率无明显相关性,因此本研究与该研究结果一致,腹透液IL⁃36浓度和PET试验中4h超滤量无明显相关性,但IL⁃36α 仍然是CAPD患者发生不良事件的独立预测因素。

  • 在随访的111例CAPD患者中,63%属于H/HA组,比例与其他多中心的研究结果一致(47.4%~83.0%)[718];在临床指标中,我们发现相较于L/LA组,H/HA组伴有更低的白蛋白和血红蛋白水平,其可能原因是:①随着腹膜溶质转运速率增高,往往伴随着更高的白蛋白以及铁蛋白清除率;②葡萄糖快速以及大量入血后降低患者食欲,减少蛋白质等营养物质摄入;③H/HA组微炎症状态较重,而炎症因子会抑制促红细胞生成素活性,加重肾性贫血[19-21]。另外本研究数据表明H/HA组患者血磷水平较L/LA组明显降低,Bernardo等[22] 报道血磷的腹膜转运速率与D/P Cr有明显相关性,与本研究的结果相一致。

  • IL⁃36基因位于人类2号染色体上,研究表明IL⁃ 36是IL⁃1家族中重要的促炎因子,能够促进炎症反应并成为自身免疫性疾病的治疗靶点。IL⁃36α、IL⁃ 36β、IL⁃36γ信号通过结合其受体IL⁃36R,招募IL⁃1受体辅助蛋白(IL ⁃1RAcP)激活下游NF ⁃κB以及MAPK炎症信号通路,此外IL⁃36还可以通过M2型巨噬细胞、朗格汉斯细胞产生炎症因子,增强Th1和Th17的反应,同时在对固有免疫反应的调控中发挥重要作用[823]。本研究发现H/HA组较L/LA组,腹透流出液中IL⁃36α、IL⁃36γ以及IL⁃6水平均显著升高,因此IL⁃36α及IL⁃36γ在腹透液中表达水平增高能够提示腹腔微炎症状态加重;另外随着IL⁃36α、IL⁃36γ 水平的增高,其可进一步通过活化炎症反应加重腹膜损伤。目前大量研究表明IL⁃36在不同类型细胞中表达和分泌,如T淋巴细胞、单核/巨噬细胞、上皮细胞等[923],而本研究发现血清中IL⁃36的水平在H/HA组与L/LA组中无明显变化,提示腹腔中表达增多的IL⁃36主要来源于腹膜固有细胞。针对IL⁃36的不同亚型,本研究发现腹透流出液中IL⁃36α与IL⁃36γ的表达与腹膜溶质转运速率相关,而IL⁃36β水平在H/HA组与L/LA组中无明显变化。既往研究表明,系统性红斑狼疮患者以及炎症性肠病患者中血清IL⁃ 36α与IL⁃36γ较健康组显著升高,且与疾病进展相关; 而视神经脊髓炎患者血清IL⁃36β与IL⁃36γ表达水平较健康人群高[9-10],但IL⁃36α水平与健康人群无明显差异。因此IL⁃36α、IL⁃36β、IL⁃36γ在不同疾病以及组织中的表达和作用不尽相同,有待进一步研究。

  • 本研究存在着一些局限性,首先这是一项单中心研究,样本量较少,仍需在多中心、大样本的人群中验证;本研究随访时间相对较短,对于肾脏不良事件的观察具有局限性,未能动态检测患者腹透流出液中IL⁃36的变化;针对IL⁃36来源于腹膜中的具体细胞类型,以及IL⁃36对腹膜纤维化的影响需要动物及细胞实验进一步研究。

  • 综上所述,本研究发现腹透流出液中IL⁃36α与IL⁃36γ可能是由腹膜固有细胞直接产生和分泌,其表达水平和腹膜损伤程度密切相关,能够用于监测和判断腹膜转运类型,并具有较高的灵敏度和特异床;腹透流出液中IL⁃36α是CAPD患者出现不良事件的独立预测因素。因此,检测CAPD患者腹透流出液中IL⁃36水平,对于临床上判断腹膜透析转运类型、早期调整腹透方案、判断腹透患者预后等可能具有重要参考价值。

  • 参考文献

    • [1] WILKIE M,DAVIES S.Insights on peritoneal dialysis in China[J].Perit Dial Int,2018,38(Suppl 2):S16-S18

    • [2] LI P K,CHOW K M,VAN DE LUIJTGAARDEN M W,et al.Changes in the worldwide epidemiology of peritoneal dialysis[J].Nat Rev Nephrol,2017,13(2):90-103

    • [3] 王友云,杜浩昌.持续非卧床腹膜透析患者营养综合评估及相关分析[J].南京医科大学学报(自然科学版),2017,37(5):639-641

    • [4] KAWANISHI H,FUJIMORI A,TSUCHIDA K,et al.Markers in peritoneal effluent for withdrawal from peritoneal dialysis:multicenter prospective study in Japan[J].Adv Perit Dial,2005,21:134-138

    • [5] MEHROTRA R,RAVEL V,STREJA E,et al.Peritoneal equilibration test and patient outcomes[J].Clin J Am Soc Nephrol,2015,10(11):1990-2001

    • [6] YANG X,TONG Y,YAN H,et al.High intraperitoneal in⁃ terleukin⁃6 levels predict peritonitis in peritoneal dialysis patients:a prospective cohort study[J].Am J Nephrol,2018,47(5):317-324

    • [7] LAMBIE M R,CHESS J,SUMMERS A M,et al.Peritoneal inflammation precedes encapsulating peritoneal sclerosis:results from the GLOBAL fluid study[J].Nephrol Dial Transplant,2016,31(3):480-486

    • [8] HIZ P,KANBUR E,DEMIR N,et al.Roles of novel IL⁃1 family(IL⁃36,IL⁃37,and IL⁃38)members in chronic brucellosis[J].Cytokine,2020,135:155211

    • [9] CHU M,WONG C K,CAI Z,et al.Elevated expression and pro ⁃ inflammatory activity of IL ⁃ 36 in patients with systemic lupus erythematosus[J].Molecules,2015,20(10):19588-19604

    • [10] YANG C S,ZHANG Q X,DENG Y,et al.Increased serum IL ⁃ 36beta and IL ⁃ 36gamma levels in patients with neuromyelitis optica spectrum disorders:association with disease activity[J].BMC Neurol,2019,19(1):185

    • [11] MEHROTRA R,DEVUYST O,DAVIES S J,et al.The current state of peritoneal dialysis[J].J Am Soc Nephrol,2016,27(11):3238-3252

    • [12] CHURCHILL D N,THORPE K E,NOLPH K D,et al.In⁃ creased peritoneal membrane transport is associated with decreased patient and technique survival for continuous peritoneal dialysis patients.The Canada⁃USA(CANUSA)Peritoneal Dialysis Study Group[J].J Am Soc Nephrol,1998,9(7):1285-1292

    • [13] WILLIAMS J D,CRAIG K J,TOPLEY N,et al.Morphologic changes in the peritoneal membrane of patients with renal disease[J].J Am Soc Nephrol,2002,13(2):470-479

    • [14] YANEZ⁃MO M,LARA⁃PEZZI E,SELGAS R,et al.Peritoneal dialysis and epithelial ⁃to ⁃ mesenchymal transition of mesothelial cells[J].N Engl J Med,2003,348(5):403-413

    • [15] TOMINO Y.Mechanisms and interventions in peritoneal fibrosis[J].Clin Exp Nephrol,2012,16(1):109-114

    • [16] KREDIET R T,STRUIJK D G.Peritoneal changes in patients on long ⁃ term peritoneal dialysis[J].Nat Rev Nephrol,2013,9(7):419-429

    • [17] HIRAHARA I,INOUE M,OKUDA K,et al.The potential of matrix metalloproteinase⁃2 as a marker of peritoneal in⁃jury,increased solute transport,or progression to encapsulating peritoneal sclerosis during peritoneal dialysis:a multicentre study in Japan[J].Nephrol Dial Transplant,2007,22(2):560-567

    • [18] KANG D H,YOON K I,CHOI K B,et al.Relationship of peritoneal membrane transport characteristics to the nutritional status in CAPD patients[J].Nephrol Dial Transplant,1999,14(7):1715-1722

    • [19] LIU Y,HUANG R,GUO Q,et al.Baseline higher peritoneal transport had been associated with worse nutritional status of incident continuous ambulatory peritoneal dialysis patients in Southern China:a 1⁃year prospective study [J].Br J Nutr,2015,114(3):398-405

    • [20] LIM P S,CHEN H P,CHEN C H,et al.Association be⁃ tween redox status of serum albumin and peritoneal membrane transport properties in patients on peritoneal dialysis[J].Blood Purif,2015,40(3):243-249

    • [21] ASANO M,ISHII T,HIRAYAMA A,et al.Differences in peritoneal solute transport rates in peritoneal dialysis[J].Clin Exp Nephrol,2019,23(1):122-134

    • [22] BERNARDO A P,CONTESSE S A,BAJO M A,et al.Peritoneal membrane phosphate transport status:a corner⁃ stone in phosphate handling in peritoneal dialysis[J].Clin J Am Soc Nephrol,2011,6(3):591-597

    • [23] NEURATH M F.IL⁃36 in chronic inflammation and cancer[J].Cytokine Growth Factor Rev,2020,55:70-79

  • 参考文献

    • [1] WILKIE M,DAVIES S.Insights on peritoneal dialysis in China[J].Perit Dial Int,2018,38(Suppl 2):S16-S18

    • [2] LI P K,CHOW K M,VAN DE LUIJTGAARDEN M W,et al.Changes in the worldwide epidemiology of peritoneal dialysis[J].Nat Rev Nephrol,2017,13(2):90-103

    • [3] 王友云,杜浩昌.持续非卧床腹膜透析患者营养综合评估及相关分析[J].南京医科大学学报(自然科学版),2017,37(5):639-641

    • [4] KAWANISHI H,FUJIMORI A,TSUCHIDA K,et al.Markers in peritoneal effluent for withdrawal from peritoneal dialysis:multicenter prospective study in Japan[J].Adv Perit Dial,2005,21:134-138

    • [5] MEHROTRA R,RAVEL V,STREJA E,et al.Peritoneal equilibration test and patient outcomes[J].Clin J Am Soc Nephrol,2015,10(11):1990-2001

    • [6] YANG X,TONG Y,YAN H,et al.High intraperitoneal in⁃ terleukin⁃6 levels predict peritonitis in peritoneal dialysis patients:a prospective cohort study[J].Am J Nephrol,2018,47(5):317-324

    • [7] LAMBIE M R,CHESS J,SUMMERS A M,et al.Peritoneal inflammation precedes encapsulating peritoneal sclerosis:results from the GLOBAL fluid study[J].Nephrol Dial Transplant,2016,31(3):480-486

    • [8] HIZ P,KANBUR E,DEMIR N,et al.Roles of novel IL⁃1 family(IL⁃36,IL⁃37,and IL⁃38)members in chronic brucellosis[J].Cytokine,2020,135:155211

    • [9] CHU M,WONG C K,CAI Z,et al.Elevated expression and pro ⁃ inflammatory activity of IL ⁃ 36 in patients with systemic lupus erythematosus[J].Molecules,2015,20(10):19588-19604

    • [10] YANG C S,ZHANG Q X,DENG Y,et al.Increased serum IL ⁃ 36beta and IL ⁃ 36gamma levels in patients with neuromyelitis optica spectrum disorders:association with disease activity[J].BMC Neurol,2019,19(1):185

    • [11] MEHROTRA R,DEVUYST O,DAVIES S J,et al.The current state of peritoneal dialysis[J].J Am Soc Nephrol,2016,27(11):3238-3252

    • [12] CHURCHILL D N,THORPE K E,NOLPH K D,et al.In⁃ creased peritoneal membrane transport is associated with decreased patient and technique survival for continuous peritoneal dialysis patients.The Canada⁃USA(CANUSA)Peritoneal Dialysis Study Group[J].J Am Soc Nephrol,1998,9(7):1285-1292

    • [13] WILLIAMS J D,CRAIG K J,TOPLEY N,et al.Morphologic changes in the peritoneal membrane of patients with renal disease[J].J Am Soc Nephrol,2002,13(2):470-479

    • [14] YANEZ⁃MO M,LARA⁃PEZZI E,SELGAS R,et al.Peritoneal dialysis and epithelial ⁃to ⁃ mesenchymal transition of mesothelial cells[J].N Engl J Med,2003,348(5):403-413

    • [15] TOMINO Y.Mechanisms and interventions in peritoneal fibrosis[J].Clin Exp Nephrol,2012,16(1):109-114

    • [16] KREDIET R T,STRUIJK D G.Peritoneal changes in patients on long ⁃ term peritoneal dialysis[J].Nat Rev Nephrol,2013,9(7):419-429

    • [17] HIRAHARA I,INOUE M,OKUDA K,et al.The potential of matrix metalloproteinase⁃2 as a marker of peritoneal in⁃jury,increased solute transport,or progression to encapsulating peritoneal sclerosis during peritoneal dialysis:a multicentre study in Japan[J].Nephrol Dial Transplant,2007,22(2):560-567

    • [18] KANG D H,YOON K I,CHOI K B,et al.Relationship of peritoneal membrane transport characteristics to the nutritional status in CAPD patients[J].Nephrol Dial Transplant,1999,14(7):1715-1722

    • [19] LIU Y,HUANG R,GUO Q,et al.Baseline higher peritoneal transport had been associated with worse nutritional status of incident continuous ambulatory peritoneal dialysis patients in Southern China:a 1⁃year prospective study [J].Br J Nutr,2015,114(3):398-405

    • [20] LIM P S,CHEN H P,CHEN C H,et al.Association be⁃ tween redox status of serum albumin and peritoneal membrane transport properties in patients on peritoneal dialysis[J].Blood Purif,2015,40(3):243-249

    • [21] ASANO M,ISHII T,HIRAYAMA A,et al.Differences in peritoneal solute transport rates in peritoneal dialysis[J].Clin Exp Nephrol,2019,23(1):122-134

    • [22] BERNARDO A P,CONTESSE S A,BAJO M A,et al.Peritoneal membrane phosphate transport status:a corner⁃ stone in phosphate handling in peritoneal dialysis[J].Clin J Am Soc Nephrol,2011,6(3):591-597

    • [23] NEURATH M F.IL⁃36 in chronic inflammation and cancer[J].Cytokine Growth Factor Rev,2020,55:70-79