第二军医大学学报  2020, Vol. 41 Issue (12): 1394-1397   PDF    
引用本文
闫嘉, 王玉洁, 周琪, 李茂婷, 赵丽芳, 杜俊, 王铁云, 李娟, 汪海燕, 赖学莉, 郭志勇. 多囊肾病与非多囊肾病患者发生腹膜透析相关腹膜炎的比较[J]. 第二军医大学学报, 2020, 41(12): 1394-1397  
YAN Jia, WANG Yu-jie, ZHOU Qi, LI Mao-ting, ZHAO Li-fang, DU Jun, WANG Tie-yun, LI Juan, WANG Hai-yan, LAI Xue-li, GUO Zhi-yong. Comparison of peritoneal dialysis-related peritonitis between patients with polycystic and non-polycystic kidney disease[J]. Academic Journal of Second Military Medical University, 2020, 41(12): 1394-1397 (in Chinese with English abstract)  
多囊肾病与非多囊肾病患者发生腹膜透析相关腹膜炎的比较
闫嘉, 王玉洁, 周琪, 李茂婷, 赵丽芳, 杜俊, 王铁云, 李娟, 汪海燕, 赖学莉, 郭志勇     
海军军医大学(第二军医大学)长海医院肾内科, 上海 200433
收稿日期: 2020-02-13    接受日期: 2020-04-03
基金项目: 国家自然科学基金（81770763，81800678），上海市科学技术委员会科技创新行动计划（18441905900）.
作者简介: 闫嘉, 博士生.E-mail:892423949@qq.com.
通信作者(Corresponding author): 郭志勇, Tel:021-31161418, E-mail:drgouzhiyong@163.com.
摘要: 目的 探讨多囊肾病（PKD）的存在是否增加腹膜透析患者腹膜炎的发生风险。方法 收集2008年1月1日至2018年12月31日在海军军医大学（第二军医大学）长海医院接受持续性不卧床腹膜透析（CAPD）作为肾脏替代疗法患者的临床床资料，进行回顾性分析。根据患者原发病类型分为PKD组和非PKD组，根据患者年龄分为≤ 62岁组和>62岁组。透析时间按照患者CAPD开始到停止的总暴露时间来计算。对收集到的数据进行泊松回归分析，计算腹膜透析相关腹膜炎发生率（次/患者年），然后根据年龄和性别等协变量进行调整后得到95%CI并进行假设检验；对每个分组进行泊松回归分析，计算腹膜透析相关腹膜炎发作时间间隔（月）及95%CI。结果 本研究共纳入249例患者，男132例（53.01%）、女117例（46.99%），年龄（62.31±14.82）岁，PKD患者14例（5.62%）、非PKD患者235例（94.38%）。非PKD患者与PKD患者年龄分别为（62.33±15.07）岁和（62.57±10.01）岁，CAPD中位持续时间（范围）分别为42.50（1.00~137.70）个月和55.35（9.60~131.50）个月。非PKD患者和PKD患者的总体腹膜透析相关腹膜炎发生率相似（分别为0.44和0.35次/患者年），革兰阴性菌腹膜炎发生率相同（均为0.09次/患者年）。泊松回归分析结果表明，性别、年龄、是否PKD对腹膜透析相关腹膜炎发生率均无明显影响。非PKD患者和PKD患者的腹膜透析相关腹膜炎发作时间间隔分别为27.39个月（95%CI 23.90~31.91个月）和33.86个月（95%CI 19.83~116.50个月），非PKD和PKD者革兰阴性菌腹膜炎发作时间间隔分别为134.83个月（95%CI 96.00~226.41个月）和141.17个月（95%CI 81.63~521.74个月）。结论 PKD不会增加腹膜透析患者发生腹膜炎的风险。
关键词: 多囊肾疾病    腹膜透析    腹膜炎    危险性评估    
Comparison of peritoneal dialysis-related peritonitis between patients with polycystic and non-polycystic kidney disease
YAN Jia, WANG Yu-jie, ZHOU Qi, LI Mao-ting, ZHAO Li-fang, DU Jun, WANG Tie-yun, LI Juan, WANG Hai-yan, LAI Xue-li, GUO Zhi-yong     
Department of Nephrology, Changhai Hospital, Naval Medical University(Second Military Medical University), Shanghai 200433, China
Supported by National Natural Science Foundation of China (81770763, 81800678) and Technology and Innovation Action Plan of Science and Technology Commission of Shanghai Municipality (18441905900).
Abstract: Objective To investigate whether the presence of polycystic kidney disease (PKD) increases the incidence of peritoneal dialysis-related peritonitis. Methods The clinical data of 249 patients who received continuous ambulatory peritoneal dialysis (CAPD) as renal replacement therapy in Changhai Hospital of Naval Medical University (Second Military Medical University) from Jan. 1, 2008 to Dec. 31, 2018 were collected and analyzed retrospectively. According to the type of primary disease, the patients were divided into PKD and non-PKD groups; they were divided into ≤ 62 and >62 years old groups. Dialysis time was calculated from the beginning to the end of CAPD. Poisson regression was performed to calculate the incidence of peritoneal dialysis-related peritonitis (episode/patient-year). The 95% confidence interval (CI) was obtained and hypothesis test was carried out after adjusting the age, gender and other covariates. Poisson regression analysis was performed for each group to calculate the attack time interval (months) and 95% CI. Results A total of 249 patients were enrolled in this study, including 14 PKD patients (5.62%) and 235 non-PKD patients (94.38%), 132 males (53.01%) and 117 females (46.99%), aged (62.31±14.82) years. The age of non-PKD and PKD patients were (62.33±15.07) and (62.57±10.01) years, respectively. The median duration of CAPD was 42.50 (1.00-137.70) and 55.35 (9.60-131.50) months, respectively. The overall incidence of peritonitis was similar in non-PKD and PKD patients (0.44 and 0.35 episode/patient-year, respectively), and the incidence of gram-negative bacterial peritonitis was same (both 0.09 episode/patient-year). Poisson regression analysis showed that gender, age or PKD had no significant effects on the incidence of peritoneal dialysis-related peritonitis. The time intervals for each episode of peritoneal dialysis-related peritonitis in non-PKD and PKD patients were 27.39 (95% CI 23.90-31.91) and 33.86 (95% CI 19.83-116.50) months, respectively. The time intervals for each episode of gram-negative bacterial peritonitis in non-PKD and PKD patients were 134.83 (95% CI 96.00-226.41) and 141.17 (95% CI 81.63-521.74) months, respectively. Conclusion PKD does not increase the risk of peritonitis in peritoneal dialysis patients.
Key words: polycystic kidney diseases    peritoneal dialysis    peritonitis    risk assessment    

常染色体显性遗传性多囊肾病(autosomal dominant polycystic kidney disease, ADPKD)是最常见的遗传性肾病[1], 约占全球成人终末期肾病(end-stage renal disease, ESRD)病因的5%~10%[2]。ADPKD典型表现是患者出现双侧大量肾脏囊肿, 囊肿随着年龄增长不断扩大, 压迫正常肾脏组织, 导致50%以上的患者发展为ESRD[3]。腹膜透析是ESRD患者的可行性治疗方法, 但其在多囊肾病(polycystic kidney disease, PKD)患者中的应用仍存在争议[4]。传统观点认为PKD患者肾脏体积过大而导致腹腔间隙缩小, 采用腹膜透析易导致透析不足[5], 且增加腹膜炎[6]、透析液渗漏的发生风险[4, 7], 因此不推荐选择腹膜透析治疗。但近年来越来越多的文献报道PKD不是腹膜透析的禁忌证, 甚至还有研究认为PKD患者比非PKD患者腹膜透析后预后更好[8-10]。本研究通过收集PKD和非PKD患者在接受持续性不卧床腹膜透析(continuous ambulatory peritoneal dialysis, CAPD)作为肾脏替代治疗后发生腹膜炎的数据, 比较非PKD和PKD人群中腹膜透析相关腹膜炎的特点, 探讨PKD是否增加腹膜透析相关腹膜炎的发生风险。

1 资料和方法 1.1 资料来源

回顾性分析2008年1月1日至2018年12月31日在海军军医大学(第二军医大学)长海医院接受CAPD作为肾脏替代疗法的患者资料。排除病史资料不全、原发病及腹膜透析时间不明确的患者。共249例患者纳入分析, 其中14例为PKD患者, 235例为非PKD患者。

1.2 资料收集

收集所有患者性别、终止腹膜透析时的年龄、腹膜透析持续时间、发生腹膜炎的时间及每次腹膜炎的病原菌。时间线定义为CAPD开始到停止的总暴露时间。终点事件为转换透析方式、肾移植、死亡和失访。统计每例患者腹膜炎的发作次数、细菌培养情况和种类。

1.3 统计学处理

采用SPSS 21.0软件进行统计学分析。对收集到的数据进行泊松回归分析, 腹膜炎发生率以每人每年发作次数(次/患者年)表示[11], 根据年龄和性别等协变量进行调整得到95% CI并进行假设检验。对收集到的数据中每个患者组(非PKD组与PKD组、年龄≤62岁组与>62岁组)进行泊松回归分析, 计算发作时间间隔(月)及95% CI。所有泊松回归分析均采用广义估计方程拟合, 以解释事件之间可能存在的相关性。呈正态分布的计量资料以x±s表示, 偏态分布的计量资料以中位数(范围)表示, 计数资料以频次表示。检验水准(α)为0.05。

2 结果 2.1 一般资料

本研究共纳入249例患者, 男132例(53.01%), 女117例(46.99%); 年龄为26~93岁, 平均(62.31±14.82)岁; PKD患者14例(5.62%), 非PKD患者235例(94.38%)。非PKD患者与PKD患者年龄分别为(62.33±15.07)岁和(62.57±10.01)岁, CAPD中位持续时间(范围)分别为42.50(1.00~137.70)个月和55.35(9.60~131.50)个月。

2.2 腹膜透析相关腹膜炎发生情况

研究时间线内所有发作的腹膜透析相关腹膜炎共449次, 其中革兰阴性(Gram negative, G-)菌腹膜炎共92次(20.49%), 培养阴性的腹膜炎共190次(42.31%)。对所有患者分析显示, 腹膜炎发生率为0.43次/患者年(95%CI 0.40~0.47次/患者年)。非PKD患者和PKD患者的总体腹膜透析相关腹膜炎发生率相似[分别为0.44次/患者年(95% CI 0.38~0.50次/患者年)和0.35次/患者年(95% CI 0.10~0.61次/患者年)], G-菌腹膜炎发生率相同[0.09次/患者年(95% CI 0.05~0.13次/患者年)和0.09次/患者年(95% CI 0.02~0.15次/患者年)]。泊松回归分析结果表明, 年龄对腹膜炎发生率没有明显影响(Z=-0.804, P=0.421);同样, 性别(Z=-1.067, P=0.286)和是否PKD(Z=1.244, P=0.213)对腹膜炎发生率也没有明显影响。经过多次对年龄分组进行调整, 将PKD患者及非PKD患者以62岁为界限各分为2个亚组对腹膜炎的发生率进行分析, 结果见表 1。

表 1 以PKD和年龄作为分组依据的各组腹膜透析相关腹膜炎的发生情况

对所有患者的总体分析显示, 腹膜透析相关腹膜炎发作时间间隔为27.69个月(95% CI 25.82~29.85个月)。非PKD患者和PKD患者的腹膜透析相关腹膜炎发作时间间隔分别为27.39个月(95% CI 23.90~31.91个月)和33.86个月(95% CI 19.83~116.50个月)。非PKD患者和PKD患者G-菌腹膜炎发作间隔分别为134.83个月(95% CI 96.00~226.41个月)和141.17个月(95% CI 81.63~521.74个月)。将PKD患者及非PKD患者以62岁为界限各分为2个亚组对腹膜炎发作时间间隔进行分析, 结果见表 1。

在腹膜炎种类和培养结果的分组比较中, 由于PKD患者G-菌腹膜炎次数太少, 培养阴性的次数也太少, 无法进行有效的比较。见表 1。

3 讨论

既往研究发现, 腹膜透析相关并发症在PKD患者中可能发生得更频繁或发生得更严重, 原因是患者肾脏和(或)多囊肝体积增大, 导致腹腔间隙减小, 腹膜内压力增加, 致使包括疝、渗漏、腹膜炎甚至移植前的肾切除术发生, 进而导致肾衰竭的进展[4, 7, 12]。考虑到空间限制和其他腹壁并发症等潜在风险, PKD常被认为是腹膜透析治疗的相对禁忌证。然而, 在近期的一些研究中, 接受腹膜透析治疗的PKD患者和非PKD患者腹膜炎(包括G-菌腹膜炎)发生率相似[10, 13-14]。本研究也发现PKD并不增加腹膜透析腹膜炎的发生风险。因此, 对于PKD患者使用腹膜透析作为肾脏替代治疗手段是安全的。此外, 人们普遍认为腹膜透析腹壁并发症对其技术生存率有负面影响[15]。腹膜透析时腹腔填塞导致腹内压增加, 引起腹壁并发症导致腹膜透析持续时间变短从而导致技术失败[4]。我们在本次数据收集中还注意到, 很多患者退出腹膜透析是由于腹膜炎所致, 没有因腹壁并发症退出腹膜透析的患者, 后续工作中我们将进一步统计分析患者退出腹膜透析的原因。

腹膜炎是腹膜透析技术失败的主要原因[16]。国际腹膜透析学会(International Society for Peritoneal Dialysis, ISPD)治疗指南强调一旦怀疑腹膜炎应进行经验性抗生素治疗[17], 及时发现致病菌对于抗生素方案的选择至关重要。但是简单的革兰染色在大多数情况下无法显示具体致病菌感染情况, 而标准的细菌培养技术却至少需要2~3 d[18]。此外, 在大多数透析中心, 15%的患者不能用标准技术鉴别致病菌[19]。本研究也发现有的患者腹膜炎并未检测出具体致病菌, 培养阴性的结果占到42.31%(190/449)。尽管致病菌的确定对腹膜炎的治疗十分重要, 但目前仍缺乏可以快速准确地检测出致病菌的方法, 有待进一步研究。

目前已有不少针对PKD使用腹膜透析作为替代治疗的研究[3, 13, 20-23], 在这些小样本研究中得到的结论多为PKD不会增加腹膜透析中发生腹膜炎的风险, 而且PKD与非PKD患者行腹膜透析治疗的临床事件及结局也无明显差异, 其他腹膜感染和并发症发生情况也无明显差异。本研究也发现PKD患者和非PKD患者中CAPD中腹膜炎的发生率无明显差异, 这与Yang等[22]、Li等[3]的研究结果一致。但是本研究结果显示患者年龄与腹膜炎发生率无关, 与Pandya等[11]的研究结果存在差异, 但与Janeiro等[13]的研究结果相似。这可能是因为PKD患者样本量太小, 没有统一的患者选择标准, 无法得出有效的比较结果; 也可能与各种客观因素(如环境因素、技术因素、患者生活条件因素等)差异而导致结果不同; 此外, 随着技术的发展与改进, 患者年龄、基础疾病等因素对腹膜透析相关并发症的影响可能逐渐降低, 但还需进一步证实。

本研究是回顾性单中心研究, 存在样本量小、病例数有限带来的偏倚, 虽然本研究选取了11年的病例, 但PKD仅有14例, 发生G-菌腹膜炎事件数更是有限, 无法进一步分析。此外, 本研究未收集到肾脏大小或其他代替内脏大小的指标(如腰围), 无法充分评价腹腔容积、有效腹膜交换面积与临床结局之间的关系。即使如此, 本研究结果至少可以说明PKD不会增加腹膜透析中腹膜炎的发生风险。对于发展为ESRD的PKD患者, 腹膜透析是一种安全有效的长期肾脏替代治疗方式。

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