【作者】 杨艳；

【导师】 王静；

【作者基本信息】 兰州大学 ， 肾脏病学， 2018， 硕士

【摘要】 目的本研究通过调查慢性肾脏病（CKD）患者膳食摄入情况,了解膳食营养素的达标率及膳食结构,蛋白质-能量消耗（PEW）的发生率及PEW的相关的风险因素,并探索CKD患者PEW的早期预警指标。方法1.分别纳入兰州大学第二医院肾内科就诊的CKD患者354例（第一部分）,93例（第二/三部分）,114例（第四部分）。按照2002年K/DOQI指南将研究对象分为CKD1⁵期;根据2008年ISRNM提出的PEW的诊断标准,将CKD患者分为PEW组和非PEW组。2.收集患者临床数据及人体测量数据,3日食物消费数据,使用上海臻鼎科技健康管理系统进行膳食营养素统计;收集患者外周血,采用双抗体夹心酶联免疫吸附法及实时定量PCR方法分别测定FGF23、Pin1、Wnt1、β-Catenin及DKK1 5项指标。3.运用SPSS21.0统计软件对数据进行分析。结果1.第一部分对慢性肾脏病患者的蛋白质-能量消耗的调查分析354例CKD1⁵期患者能量达标人数为88例（24.8%）,蛋白质达标32例（9%）,脂质达标51例（14.4%）,碳水化合物达标88例（24.9%）;Alb达标173例（33.1%）,HB达标117例（32.1%）,BMI达标165例（46.6%）。对267例患者进行了PEW评估,PEW发生总人数为151例（56.6%）。CKD1⁵期患者PEW的发生率依次为6.2%,29.6%,42.1%,50.0%和70.9%。随着CKD进展PEW的发生率逐渐增加。2.第二部分慢性肾脏病患者的膳食调查分析93例肾病膳食指导问卷调查:40例（43%）患者未进行膳食指导,6例（7%）患者经网络平台咨询,47例（50%）患者经肾内专科营养师指导。CKD患者蛋白质及碳水化合物、钠、磷摄入超标,膳食纤维、钙、碘及叶酸的摄入严重不足。膳食中蛋白质来源中非优质植物蛋白、动物蛋白及豆类蛋白三组间具有统计学意义（F=123.02,P<0.001）。CKD各期患者蔬菜类及家禽类摄入量随着CKD进展摄入逐渐减少,组间有统计学意义（P<0.05）。膳食中供能以中、晚餐为主,早餐所占比例整体低下。3.第三部分慢性肾脏病患者蛋白质-能量消耗的相关因素分析93例CKD患者中PEW共28例,CKD1⁵期PEW发生率依次10.3%,10.0%,32.0%,43.8%及69.2%。与非PEW组相比,PEW组患者一般指标:身体质量指数指数（BMI）、体重、体重下降,实验室指标:白蛋白（Alb）、前白蛋白（PA）、总胆固醇（CHO）、血肌酐（Scr）、估计肾小球滤过率（eGFR）和人体成分:体脂比、上臂肌围、肩胛下皮褶厚度、握力及营养学指标:总能量、蛋白质、碳水化合物、膳食纤维、叶酸、铁、硒、铜、锰、锌、钾、磷、维生素B₁、碘、烟酸及所有氨基酸),组间有统计学差异（P<0.05）。多因素logistic回归分析示:PA降低、CHO降低、e GFR降低、BMI降低、握力减少、主食摄入不足、总能量及钾摄入不足均为PEW的风险因素。4.第四部分骨特异性分子标记物与慢性肾脏病患者蛋白质-能量消耗关系的研究114例CKD患者中诊断PEW共63例。与非PEW组比较,PEW组临床指标（Alb、CHO、eGFR）较非PEW组低而Scr较PEW组高,两组间有统计学意义（P<0.05）,PEW组中伴随体重下降、膳食摄入减少,合并糖尿病及心脏疾病的患者比例高于非PEW组,组间有统计学意义（P<0.05）;Pearson相关分析示:血清FGF23水平与PEW呈正相关（r=0.281,P=0.049）;logistic回归分析示:血清FGF23和Wnt1水平分别是PEW的风险因素,血清FGF23 ROC曲线下面积为0.659,血清Wnt1ROC曲线下面积为0.593,均具有一定诊断价值。各标记物RNA水平均与PEW无相关性。结论1.CKD患者对营养治疗知晓率低;膳食摄入不足,随着CKD的进展营养素达标率低下;膳食结构不合理。2.CKD患者PEW发生率随着疾病进展逐渐升高。PA降低、CHO降低、eGFR降低、BMI降低、握力减少、主食摄入不足、总能量及钾摄入不足可能为PEW的风险因素。3骨特异性标记物FGF23有望成为PEW早期诊断的血清学标志物,Wnt信号通路相关蛋白与PEW的关系有待需要进一步研究。4.需要对所有CKD患者需要进行目标营养管理,实行个体化膳食指导甚至进行营养治疗。更多还原

【Abstract】 Objective To acquire the compliance rate of nutrients,the incidence of protein-energy wasting（PEW）and dietary pattern by diet investigation in paitents with chronic kidney disease（CKD）.Analyzing the relevant risk factors of PEW and researching the early warning of PEW.Methods The study enrolled patients with CKD in Lanzhou University Second Hospital,and the number of patients was 354,93,93 and 114 in four parts,respectively.They were divided into5 stages by K/DOQI guideline in 2002,and according to the PEW diagnostic criteria by ISRNM recommended in 2008,patients were divided into the PEW group and the non-PEW group.We collected the clinical indexs,anthropometrics data and food consumption data in three days,which was analyzed by Shanghai Zhengding Technology Health Management System.While peripheral blood was collected from patients,and five indicators of FGF23,Pin1,Wnt1,β-Catenin,and DKK1were measured by double antibody sandwich enzyme-linked immunosorbent assay and real-time quantitative PCR.Using SPSS21.0 statistical software to analyze the data.Results1.Part 1 Analysis on the protein-energy wasting among patients with chronic kidney diseaseThe study included 354 patients divided in CKD1⁵ stages.The number of patients reached the energy recommendation was 88 and totally compliance rate was 24.8 percent while protein recommendation was 32（9%）;and there were 51 patients with CKD reaching the recommendation about 14.4 percent.Carbohydrate up to recommendation was for 88 patients and compliance rate was 24.9 percent.The patients for clinical indexs of albumin and hemoglobin up to the standard was173（33.1%）and 117（32.1%）,respectively.The number of patients reached the body mass index（BMI）recommendation was 165 and compliance rate was 46.6 percent.There were 151patients with PEW about 56.6 percent,and the incidence of PEW in 267 patients with the stages CKD1⁵ was 6.2%,29.6%,42.15%,50.0%and 70.9%,successively.In total,these indexes mentioned above was gradually decreased but the incidence of PEW was increased with the progress of CKD.2.Part 2 Investigating the diet of patients with chronic kidney diseaseThe results for the research about dietary in 93 CKD patients showed that forty patients（43%）had no dietary guidance,while six patients（7%）were consulted online,and forty-seven patients（50%）were guided by specialist dietitian in nephrology department.The intake of protein,carbohydrate,sodium and phosphorus were exceeded,while dietary fiber,calcium,iodine and folic acid were less than 50%to the standard.Protein sources by non-high quality plant protein,animal protein and legumes were statistically significant（F=123.02,P<0.001）.The vegetable and poultry groups gradually decreased with the development of CKD,and there was statistically significant difference between the groups（P<0.05）.Patients with CKD1⁵ stages were mainly served with lunch and dinner,but the proportion of energy for breakfast was low.3.Part 3 Analysis on the related factors of protein-energy wasting in patients with chronic kidney diseaseThere were 28 cases with PEW in 93 CKD patients,and the incidence rate of PEW in CKD1⁵ stages was 10.3%,10.0%,32.0%,43.8%and 69.2%.Compared with the non-PEW group,BMI,weight,and weight loss,albumin,cholesterol,serum creatinine,eGFR,body fat ratio,arm muscle circumference（AMC）,subscapular skinfold（SSF）,grip strength,total energy,protein,carbohydrates,dietary fiber,folic acid,iron,selenium,copper,manganese,zinc,potassium,phosphorus,vitamin B₁,iodine,nicotinic acid and amino acids all had statistical significance（P<0.05）.Multivariate logistic regression analysis showed that the decasesed prealbumin,cholesterol,eGFR,BMI and grip strength,and insufficient staple food,total energy and potassium probably were all risk factors for PEW.4.Part 4 Research on the relationship between bone specific molecular markers and protein-energy wasting in patients with chronic kidney diseaseCompared with the non-PEW group,there were significantly decreased in albumin,cholesterol,eGFR in PEW group（P<0.05）,while the serum creatinine was increased（P<0.05）,and the proportion of patients with weight loss,dietary intake,or diabetes mellitus and cardiovascular disease in PEW group was higher（P<0.05）.Pearson correlation analysis showed that serum FGF23concentrations were significantly and positively correlated with PEW（r=0.281,P=0.049）.Univariate and multivariate logistic regression analysis indicated that serum FGF23 and Wnt1 were the independent predictor of PEW.The area under ROC curve was used to estimate the diagnostic critical value of PEW and the area under ROC curve serum FGF23 was 0.659,and the area under ROC curve serum Wnt1 was 0.593.In contrast,there was no correlation between the five markers in RNA levels and PEW.Conclusions1.Nutritional therapy has not been paid enough attention to patients with CKD.Under the progress of CKD,the dietary intake is significent deficiency and the dietary structure is not reasonable.2.The incidence of PEW in patients with CKD gradually increases with the progress of disease.It is possiblely that the decasesed prealbumin,cholesterol,eGFR,BMI and grip,and insufficient staple food,total energy and potassium are all the risk factors of PEW.3.The incidence of PEW is gradually increased with the progress of CKD.FGF23 is expected to be a serological marker of early diagnosis of PEW,while the relationship of Wnt signaling pathway associated proteins and PEW requires further study to confirm.4.All patients with CKD need to implement target nutrition management by practicing individual dietary guidance and goal nutrition therapy.更多还原