腹膜透析患者营养不良-炎症-心血管疾病与认知功能恶化的关系

doi:10.19723/j.issn.1671-167X.2019.03.020

北京大学学报（医学版） ›› 2019, Vol. 51 ›› Issue (3): 510-518. doi: 10.19723/j.issn.1671-167X.2019.03.020

腹膜透析患者营养不良-炎症-心血管疾病与认知功能恶化的关系

段丽萍¹,郑朝霞¹,张宇慧²,董捷^2△()

^1. 邯郸市中心医院肾内一科,河北邯郸 056001
^2. 北京大学第一医院肾内科,北京大学肾脏病研究所,卫生部重点实验室,教育部慢性肾脏病防治重点实验室,北京 100034

收稿日期:2019-03-18 出版日期:2019-05-09 发布日期:2019-06-26
作者简介:董捷,主任医师,教授,博士生导师。1995年毕业于北京医科大学(现称北京大学医学部), 2002年获北京大学第一医院肾内科临床博士学位,2008—2009年作为访问学者于美国Vanderbilt大学肾内科学习。近来获得的主要奖项有:国际腹膜透析学会奖学金(2009年),国际肾脏营养及代谢学会颁发全球研究奖励(2010年),教育部新世纪人才(2011年),北京大学医学部青年学者奖(2012年),国际腹膜透析学会John Maher奖(2018年),“荣耀医者”青年创新奖(2018年)。社会任职:Peritoneal Dialysis International 编委,国际腹膜透析学会教育委员会委员,中国非公医院协会肾脏病和透析专委会腹膜透析学组组长,北京医学会腹膜透析专委会主任委员,北京医学会血液净化分会副主任委员,北京医师协会理事,北京医学会临床营养分会常务委员,《中国血液净化杂志》编委,《中华肾脏病杂志》编委,北京血液透析质量控制中心专家,中华医学会肾脏病分会血液净化学组专家。近年主持课题及科研成果:主持首都临床应用特色专项基金3项,其中1项为重点项目;国际肾脏病学会GO R&P Committee临床研究基金1项,国际肾脏营养代谢学会临床研究基金1项,横向研究基金数项,参与多项国家自然科学基金和教育部创新团体基金研究,并获国家专利局实用新型6项,发明专利3项。领导的腹透课题组发表SCI论文60余篇,中文论文近100篇。参编国际腹膜透析学会指南2017-2019:腹透导管相关感染,透析充分性指南。参编《肾脏病学》第3版、第4版,《肾脏病学临床概览》《血液净化手册》《肾脏病临床病例摘要精选》《Handbook of Nutrition and the Kidney, 7th edition》《泌尿病学》,主编《我们的腹透人生》。多次在国际腹透学术年会和全国肾脏病年会及血液净化论坛上应邀报告。
基金资助:
中国教育部新世纪优秀人才奖,中国百特公司临床研究奖和全球拓展研究与预防委员会国际肾脏病研究奖

Association of malnutrition-inflammation-cardiovascular disease with cognitive deterioration in peritoneal dialysis patients

Li-ping DUAN¹,Zhao-xia ZHENG¹,Yu-hui ZHANG²,Jie DONG^2△()

^1. Handan Central Hospital, Department 1 of Nephrology, Handan 056001, Hebei, China
^2. Renal Division, Department of Medicine; Institute of Nephrology, Peking University First Hospital; Key Laboratory of Renal Disease, Ministry of Health of China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education, Beijing 100034, China

Received:2019-03-18 Online:2019-05-09 Published:2019-06-26
Supported by:
Supported by the NEW Century Excellent Talents from Education Department of China, the Baxer Clinical Research Award from Baxer Corp of China,and International Society of Nephrology Research Award from the Global Outreach Research and Prevention Committee

摘要/Abstract

摘要： 目的探讨腹膜透析(peritoneal dialysis, PD)患者存在的营养不良-炎症状态-心血管疾病(动脉硬化)(malnutrition-inflammation-atherosclerosis,MIA)综合征与认知功能恶化的关系。方法采用前瞻性纵向队列研究,于2013年3—11月,对符合入选标准的腹膜透析患者完成总体和特定认知功能测定,结合基线是否有心血管疾病病史,白蛋白≤35 g/L,超敏C-反应蛋白(high-sensitive C-reactive protein, hs-CRP)≥3 mg/L,将患者分为MIA0(全为否)、MIA1(1项为是)、MIA2(≥2项为是)3个组,并于随访2年后对患者重复认知功能测定。采用卡方检验、单因素方差分析、Kruskal-Wallis H 检验比较基线及2年后组间一般资料、生化指标,以及总体和特定认知功能参数。进一步的组间多重两两比较采用Bonferroni方法调整显著性值。以每一项总体和特异认知功能得分差值为因变量,以年龄、性别、教育水平、体重指数、抑郁分数、糖尿病、血钠和MIA(MIA0为对照,MIA1和MIA2为哑变量)为自变量,以多元线性回归分析影响认知功能恶化的因素,每一项认知领域的分析都以其相应的基线参数进行校正。结果随访2年后,认知障碍(cognitive impairment, CI)的发生率从20.0%上升到24.7%。MIA2和MIA1组修正的简易智力状态检查量表(the modified mini-mental state examination, 3MS)得分下降绝对值明显高于MIA0组(-3.9±12.0 vs. 1.1±6.7, P<0.01;-2.3±11.8 vs. 1.1±6.7, P<0.05),而特定认知功能测定包括执行功能(连线试验A和B,P=0.401,P=0.176)、即时记忆(P=0.437)、延迟记忆(P=0.104)、视觉空间能力(P=0.496)和语言能力(P=0.171)的变化3组间差异无统计学意义。经多元线性回归分析,年龄、教育水平、糖尿病、抑郁等均是一项或多项认知功能恶化的危险因素,存在MIA综合征一项因素是整体认知恶化的独立危险因素(P=0.022),存在MIA综合征两项及以上因素者不仅是整体认知恶化的独立危险因素(P<0.001),而且是延迟记忆、视觉功能及语言功能恶化的独立危险因素(P=0.002,P=0.007,P=0.004)。结论腹膜透析患者存在MIA综合征一项及以上因素是总体认知功能恶化的高危人群;存在MIA综合征因素越多,患者的特异认知功能领域影响越广泛。

关键词: 腹膜透析, 炎症状态, 营养不良, 心血管疾病, 认知功能

Abstract: Objective: To investigate the relationship between malnutrition-inflammation-atherosclerosis (MIA) syndrome and deterioration of global and specific domains of cognitive function in peritoneal dialysis (PD) patients.Methods: This was a multi-center prospective cohort study. The PD patients who met the inclusion criteria were examined with general and specific cognitive function between March 2013 and November 2013. The patients were divided into MIA0, MIA1 and MIA2 groups, according to items of “Yes” for whether or not having cardiovascular disease, serum albumin≤35 g/L or high-sensitive C-reactive protein (hs-CRP) ≥3 mg/L. After 2 years, the patients maintained on PD would be repeatedly measured with cognitive function. The Chi-square test, One-way ANOVA, Kruskal-wallis H rank sum test were used to compare the differences of clinical characteristics, biochemical data, and global and specific cognitive function parameters among the three groups at baseline, and two years later, respectively. The Bonferroni method was applied to adjust the significance level for further comparison between each two different groups. The change of score in each cognitive parameter of global and specific domains was used as dependent variable. Age, gender, education level, depression index, body-mass index, diabetes mellitus, serum sodium levels and MIA (MIA0 was control, MIA1 and MIA2 as dummy variables) were all included in the multivariable linear regression models to analyze the risk factors of the deterioration of cognitive function. The analysis for each cognitive domain was adjusted for the baseline score of the corresponding cognitive parameter. All the analyses were performed using SPSS for Windows, software version 25.0 (SPSS Inc., Chicago, IL). Results: Over two-year follow up, the prevalence of cognitive impairment increased from 20.0% to 24.7%, absolute decrease of 3MS scores were more significantly decreased in MIA2 (-3.9±12.0 vs. 1.1±6.7, P<0.01) and MIA1 group (-2.3±11.8 vs. 1.1±6.7, P<0.05) than those in MIA0 group respectively. Specific cognitive functions, included executive function (trail-making tests A and B, P=0.401,P=0.176), immediate memory (P=0.437), delayed memory (P=0.104), visuospatial skill (P=0.496), and language ability (P=0.171) remained unchanged. Advanced age, lower education, diabetes mellitus and depression were all correlated with the deterioration of one or more cognitive domains, and the patients having one item of MIA syndrome were prone to develop the deterioration of 3MS (P=0.022). Furthermore, the patients having two or more items of MIA syndrome were more likely to develop the deterioration of not only 3MS (P <0.001), but also delayed memory, visuospatial skill, and language ability (P=0.002, P=0.007, P=0.004, respectively).Conclusion: Patients with one item or above of MIA syndrome were at high-risk for the deterioration of global cognitive function. The more MIA syndrome items there were, the more specific cognitive domains deteriorated.

Key words: Peritoneal dialysis, Malnutrition, Inflammation, Cardiovascular disease, Cognitive function

中图分类号:

R459.5

段丽萍,郑朝霞,张宇慧,董捷. 腹膜透析患者营养不良-炎症-心血管疾病与认知功能恶化的关系[J]. 北京大学学报（医学版）, 2019, 51(3): 510-518.

Li-ping DUAN,Zhao-xia ZHENG,Yu-hui ZHANG,Jie DONG. Association of malnutrition-inflammation-cardiovascular disease with cognitive deterioration in peritoneal dialysis patients[J]. Journal of Peking University(Health Sciences), 2019, 51(3): 510-518.

图/表 4

图1

表1

腹膜透析患者一般临床指标在MIA各组基线的比较(n=440)"

Variables	MIA0	MIA1	MIA2	F/χ²	P
n(%)	141 (32.0)	153(34.8)	146 (33.2)	-
Age/years, $x ?$ ±s	47.4±13.0^*	52.5±14.1	56.1±14.2^△	14.360	0.000
Male, n(%)	70(49.6)	80(52.3)	82(56.2)	1.241	0.538
PD duration/months, M(Q1,Q3)	19.7(11.1,43.4)	26.6(12.2,53.3)	26.8(9.7,53.2)	4.514	0.105
DM, n(%)	29(20.6)	31(20.3)	46(31.5)	6.575	0.037
CVD, n(%)	0 (0.0)^*	23(15.0)^#	71(48.6)^△	106.569	0.000
hs-CRP /(mg/L), M(Q1,Q3)	0.9(0.5,1.7)^*	3.1(1.0,8.4)^#	8.7(4.1,15.7)^△	201.354	0.000
Serum albumin/(g/L), $x ?$ ±s	39.8±3.0^*	36.4±5.1^#	32.3±5.6^△	91.364	0.000
Depression score/scores, $x ?$ ±s	36.9±8.6^*	40.1±9.4	42.2±9.1^△	12.034	0.000
Level of education (High school and above), n(%)	90(63.8)^*	81(52.9)^#	59(40.4)^△	15.810	0.000
BMI/(kg/m²), $x ?$ ±s	22.7±3.8	22.8±3.4	22.3±3.4	1.103	0.333
Systolic blood pressure(mmHg), $x ?$ ±s	131.0±15.7^*	136.1±18.5	138.6±20.0^△	6.292	0.002
Hemoglobin/(g/L), $x ?$ ±s	109.8±13.7	106.0±17.7^#	99.0±19.4^△	14.724	0.000
Triglycerides/(mmol/L), $x ?$ ±s	1.9±1.0	2.0±1.4	2.0±1.6	0.464	0.629
Total cholesterol/(mmol/L), $x ?$ ±s	4.8±1.0	4.8±1.1	4.6±1.2	1.077	0.341
Calcium/(mmol/L), $x ?$ ±s	2.3±0.2	2.3±0.3^#	2.2±0.3^△	11.617	0.000
Serum sodium/(mmol/L), $x ?$ ±s	139.5±2.7	138.3±11.3	139.2±3.5	1.186	0.306
RRF/(ml/min), M(Q1,Q3)	2.9(0.5,7.4)	2.0(0.0,5.6)	2.1(0.0,5.1)^△	8.030	0.018
Total kt/V, $x ?$ ±s	2.0±0.4	1.9±0.4	1.8±0.4	2.810	0.061
Total CCR/(L/w), $x ?$ ±s	60.5±19.2	57.7±17.1	57.2±17.3	1.345	0.262

表1

表2

腹膜透析患者MIA各组基线整体及特异认知功能参数的比较(n=440)"

Variable	MIA0(n=141)	MIA1(n=153)	MIA2(n=146)	F/χ²	P
3MS/scores, $x ?$ ±s	89.2±7.8^*	85.1±10.4^#	79.5±15.6^△	24.734	0.000
CI, n(%)	12(8.5)	27(17.6)^#	49(33.6)^△	28.945	0.000
Trails A/s, M(Q1,Q3)	60.0(45.0,75.0)^*	69.0(46.5,96.5)^#	80.0(55.0,121.8)^△	26.029	0.000
Trails B/s, M(Q1,Q3)	130.0(100.0,199.0)	153.5(104.8,237.0)	183.0(119.3,293.0)^△	18.489	0.000
Immediate memory/scores, $x ?$ ±s	78.1±17.5	74.5±17.1^#	69.1±18.1^△	9.599	0.000
Delayed memory/scores, $x ?$ ±s	92.9±14.1	90.8±16.0^#	84.5±19.5^△	9.840	0.000
Visuospatial skill/scores, $x ?$ ±s	90.7±23.1	86.8±22.9	81.5±23.8^△	5.407	0.005
Language ability/scores, $x ?$ ±s	95.7±12.6	94.9±12.2^#	89.7±14.2^△	8.909	0.000

表2

表3

腹膜透析患者随访2年后整体及特异认知参数变化差值在MIA各组的比较(n=285)"

Variable	MIA0 (n=89)	MIA1 (n=106)	MIA2 (n=90)	F/χ²	P
3MS/scores, $x ?$ ±s	1.1±6.7^*	-2.3±11.8	-3.9±12.0^△	5.227	0.006
Trails A/s, M(Q1,Q3)	-6.0(-18.0,5.0)	-10.0(-32.0,5.0)	-9.5(-30.8,9.0)	1.828	0.401
Trails B/s, M(Q1,Q3)	0.0(-31.5,35.5)	-4.0(-58.0,26.0)	-6.0(-88.5,31.0)	3.469	0.176
Immediate memory/scores, $x ?$ ±s	1.4±16.6	1.9±16.0	4.5±18.4	0.829	0.437
Delayed memory/scores, $x ?$ ±s	0.5±12.9	-1.1±16.6	-4.8±21.0	2.283	0.104
Visuospatial skill/scores, $x ?$ ±s	4.1±24.3	6.1±26.1	1.7±26.5	0.703	0.496
Language ability/scores, $x ?$ ±s	3.4±12.6	-0.0±15.1	-0.4±16.4	1.775	0.171

表3

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腹膜透析患者营养不良-炎症-心血管疾病与认知功能恶化的关系

Association of malnutrition-inflammation-cardiovascular disease with cognitive deterioration in peritoneal dialysis patients

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