【作者】 邢洁；

【导师】 完强；

【作者基本信息】 山东大学 ， 内科学（肾病）， 2017， 硕士

【摘要】 研究目的:近年来,慢性肾脏病(CKD)的发病率持续增加,已经成为全球公共卫生问题。轻中度肾脏病影响了5%-7%的世界人口,在发展中国家慢性肾脏病的发病率更高。全球范围内的流行病学的横断面调查研究表明在中国,CKD的患病率是10.8%。因此,我们需要使用简便和廉价的诊疗方法早期预测和诊断CKD,可以有效避免或延缓患者进展到终末期肾脏病(ESRD)。传统上我们认为血清中Y-谷氨酰基转移酶(GGT)水平的增高是饮酒和肝功能不全的生物学标志物,也是氧化应激早期、敏感的指标,之前还有文章得出血清中GGT水平升高是冠心病、高血压、糖尿病的独立危险因素的研究结论。氧化应激是存在于CKD患者中的普遍现象,也是CKD进展以及发生并发症的重要驱动因素。也有少量文献报道血清中GGT水平和CKD之间的关系,但是得出的研究结果是相互矛盾的。在中国,探讨血清中GGT的水平和CKD之间的相关性的大规模的前瞻性研究未见报道。因此,我们基于常规健康体检人群建立起大型的前瞻性的队列来探究和验证血清中GGT水平和CKD危险性之间的关系。研究方法:本研究基于2005-2010年山东多中心健康管理纵向监测队列数据库建立纵向体检监测队列,采用Cox比例风险回归模型探讨血清GGT水平与CKD发生之间的相关性。研究结果:1、研究队列共随访57891人年,其中1456个人逐渐发展为CKD,发病密度是25.15/1000人年。2、不同血清GGT水平,多数体检指标存在统计学差异;3、为了准确估计不同基线水平的GGT的CKD5年累计发病率,本研究根据年龄、BMI水平、是否患有高血压及是否患有糖尿病分为不同的亚组,结果发现除了糖尿病亚组,其他亚组在不同血清GGT水平下,CKD五年累计发病率差异有统计学意义;4、多因素Cox比例风险回归分析发现,在调整了多种潜在的混杂因素后,比如年龄,性别,血肌酐,身体质量指数,血清白蛋白,谷氨酸转氨酶,血红蛋白,白细胞计数,总胆固醇,甘油三酯,高血压,糖尿病,心血管疾病,吸烟,饮酒等因素后,血清GGT为CKD发生的独立危险因素(HR/95%CI,1.658/1.294-2.125,P<0.001)。5、血清GGT与CKD发生的关联存在性别差异。在男性研究对象中,CKD的发病风险随血清GGT水平的增高而增加(P for trend=0.002),Q4组CKD的发病风险是Q1组的1.346倍(95%CI为1.028-1.764),差异有统计学意义(P=0.031)。而使用log变换后的GGT与CKD发病的关联性与该结论一致(调整危险比,1.625(1.237-2.133),P<0.05)。而在女性研究对象中发现血清GGT水平和CKD的发病率无统计学联系(调整危险比,1.314(0.669-2.581),P<0.05)研究结论:血清GGT水平与CKD发生之间存在相关性,血清GGT为CKD发病的独立危险因素。更多还原

【Abstract】 ObjectiveIn recent decades,the prevalence of chronic kidney disease(CKD)continuously rises,and it has received wide attention as a global public health problem.But the awareness of CKD is still low among patients and health care providers.Milder CKD affects 5-7%of the world population and is more common in developing countries and disadvantaged populations.A nationwide epidemiological cross-sectional survey showed that the prevalence of CKD was 10.8%in China.Early detection and treatment of CKD using readily available,inexpensive therapies can slow or prevent progression to end-stage renal disease(ESRD).Serum GGT has been traditionally used as an indicator of alcohol intake or liver dysfunction.Elevated serum GGT is proposed as an early and sensitive marker of oxidative stress.Prevention of CKD should be considered in planning an oxidative stress is prevalent in CKD patients and is considered to be an important driver of CKD progression and its complications.Previous studies have shown elevated GGT levels were significant predictors of hypertension,diabetes,cardiovascular disease.Reactive oxygen species(ROS)are the most important contributor of oxidative stress in biological systems.Increased limited numbers of literatures have focused on the association between γ-glutamyltransferase(GGT)and chronic kidney disease(CKD),and their results were controversial.Therefore,in this study,we set up a large-scale cohort of Chinese population to discover and verify the association between serum GGT and CKD.MethodsBased on the 2005-2010 year Shandong multicenter health management longitudinal monitoring cohort database,a longitudinal physical examination monitoring cohort was established,and we used multivariate Cox regression model to clarify whether elevated serum GGT increased the risk of CKD or not.Results1.During the follow-up of 57,891 person-years,1456 patients developed CKD,giving rise to an incidence density of 25.15 per 1000 person-years(1456/57,891 personyears).2.Under different serum GGT grades,most of the physical indicators were statistically different;3.In order to estimate 5-year cumulative CKD incidence accurately in different baselines,subjects were divided into different subgroups according to age,BMI level,hypertension and diabetes.The results showed that all the sub-groups were statistically significant in the 5-year cumulative CKD incidence,except the diabetic subgroup.4.After multiariable Cox proportional hazards regression analysis were adjusted for a variety of potential confounding factors,such as age,gender,serum creatinine,body mass index,serum albumin,glutamic acid transaminase,hemoglobin,white blood cell count,liver cholesterol,triglycerides,high blood pressure,diabetes,cardiovascular disease,smoking,drinking,we found that serum GGT is an independent risk factors for CKD.5.After gender stratification,it was found that the association between serum GGT and CKD was sex-specific.For males in the 4th quartile,CKD risk was signifcantly increased(adjusted HR,1.346(1.028-1.764),P = 0.031),and the increasing trend can also be found(P for trend=0.002).The results were consistent for log-transformed GGT(adjusted HR,1.625(1.237-2.133),P<0.001).But there was no association between increasing GGT levels and CKD among females(P for trend=0.226 for categorical analysis,P = 0.428 for log-transformed GGT).ConlusionsThe result reveals that there is a positive relationship between increasing serum GGT levels and the incidence of CKD which suggests that elevated GGT level could be an independent indicator for risk of CKD.更多还原