血清GGT与CKD关系的前瞻性队列研究

发布时间：2018-02-25 01:32

本文关键词： 慢性肾脏病 γ-谷氨酰基转移酶队列研究 Cox回归模型　出处：《山东大学》2017年硕士论文　论文类型：学位论文

【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,P0.001)。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),P0.05)。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),P0.05)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。
[Abstract]:Objective: in recent years, the incidence of chronic kidney disease (CKD) has been increasing and has become a global public health problem. Mild to moderate kidney disease affects 5- 7% of the world's population. The incidence of chronic kidney disease is higher in developing countries. Cross-sectional epidemiological studies worldwide show that the prevalence of CKD in China is 10.8. We need to use simple and inexpensive diagnostic methods for early prediction and diagnosis of CKD, which can effectively prevent or delay the progression of patients to end stage renal disease (ESRD). Traditionally, we believe that the increase in serum levels of Y- glutamyl transferase GGTs is. The biomarkers of alcohol consumption and liver dysfunction, It is also an early and sensitive indicator of oxidative stress. Before that, it was concluded that elevated serum GGT level is an independent risk factor for coronary heart disease, hypertension and diabetes. Oxidative stress is a common phenomenon in patients with CKD. It is also an important driver of CKD progression and complications. There is also a small amount of literature about the relationship between serum GGT levels and CKD, but the results are contradictory. Large-scale prospective studies to explore the correlation between serum GGT levels and CKD have not been reported. We established a large prospective cohort based on routine health examination to explore and verify the relationship between serum GGT levels and the risk of CKD. Methods: this study was based on the longitudinal health management of multiple centers in Shandong Province from 2005 to 2010. The monitoring queue database established the longitudinal medical examination monitoring queue, Cox proportional risk regression model was used to study the correlation between serum GGT level and the incidence of CKD. Results: 1: 1, the study cohort was followed up for a total of 57891 person-years, of which 1 556 were gradually developed as CKD.The incidence density was 25.15 / 1 000 person-years, with different serum GGT levels. In order to accurately estimate the cumulative annual incidence of GGT at different baseline levels, this study was divided into different subgroups according to age and age. The results showed that in addition to the diabetes subgroup, the 5-year cumulative incidence of CKD in other subgroups was significantly different under different serum GGT levels. Multivariate Cox proportional risk regression analysis showed that after adjusting for many potential confounding factors, such as age, Sex, serum creatinine, body mass index, serum albumin, glutamate transaminase, hemoglobin, white blood cell count, total cholesterol, triglyceride, hypertension, diabetes, cardiovascular disease, smoking, drinking, etc. Serum GGT is an independent risk factor for the occurrence of CKD. The risk of CKD in the male study subjects increased with the increase of serum GGT level. The risk of CKD in group Q4 is Q1. 1 / 1.294-2.125N / 2.125A / P 0.001 / 5. There is a gender difference in the association between serum GGT and CKD. In male subjects, the risk of GGT increased with the increase of serum GGT level. The risk of CKD in group Q4 is Q1. The CI of 1.346 times and 95% CI was 1.028-1.764, the difference was statistically significant. The correlation between GGT and CKD after using log transformation was consistent with this conclusion (adjusted risk ratio: 1.6251.237-2.133P 0.05). The serum GGT level and the incidence of CKD were not found in female subjects. The study on the correlation between serum GGT level and the occurrence of CKD (adjusted risk ratio 1.3140.669-2.581P0.05) has been concluded that there is a correlation between the level of serum GGT and the occurrence of CKD. Serum GGT was an independent risk factor for the pathogenesis of CKD.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R692

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