FGF23与慢性肾脏病非透析患者肾功能损害及矿物质代谢紊乱的相关性研究

发布时间：2018-02-04 16:26

本文关键词： 慢性肾脏病 FGF23 骨代谢　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:随着人类社会的进步以及生活质量的提高,各种疾病的多发也成为困扰人们生活的不可忽视的问题。目前从全世界范围内的调查数据来看,有一种疾病的发病率越来越高,现在已经成为不得不重视的公共卫生问题,那就是慢性肾脏病(CKD)。根据文献报道,中国是CKD的高发国家之一,数据显示我国成年人群体中每10人中就有1人患慢性肾脏病,防治任务相当繁重。在CKD患者肾功能进行性下降的过程中,钙磷代谢和骨代谢异常是最常见的并发症之一,显著提高了 CKD患者的致死率,严重影响了患者的生存质量。成纤维生长因子23(FGF23)是新近发现的在钙磷代谢的调节方面起到重要作用的因子,已有研究指出FGF23参与了慢性肾脏病矿物质异常的代谢过程,并且能够预测CKD病程进展与预后。FGF23的发现对CKD患者钙磷代谢紊乱的研究有重大的意义,然而目前尚有很多作用机制尚不完全明确,过往研究中也有一些不一致的地方,因此需要进一步研究。本课题拟通过回顾性研究,检测FGF23在不同时期CKD非透析患者体内的含量差异,进一步讨论其与肾功能及矿物质代谢之间的相关性,为临床上CKD-MBD的调节及防治提供新的思路。研究方法:严格按照CKD的诊断标准,在2015年6月至2016年6月期间来山东大学第二医院肾内科住院治疗的病人中,筛选出慢性肾脏病非透析患者107例纳入研究。另外纳入研究的107人排除了恶性肿瘤、骨折、原发骨代谢疾病、原发甲状旁腺疾病等疾病。计算入选患者的肾小球滤过率,按CKD的分期标准将107例入选患者分为三组:CKD1-2期、CKD3-4期、CKD5期,病例数量分别为32例、40例、43例。收集所有患者空腹静脉血,利用ELISA试剂盒检患者血清FGF23、Klotho、25羟基维生素D(25-OH-VD)、骨碱性磷酸酶(BAP)、抗酒石酸酸性磷酸酶5b(TRACP-5b)含量,并统计患者基本临床资料(年龄、一般情况、常规用药)及生化指标(血清钙、血清磷、肌酐、胱抑素C、尿素氮、尿酸、血清白蛋白、PTH、碱性磷酸酶等)。比较各组患者上述指标的差异,并应用Pearson相关分析FGF23与骨碱性磷酸酶(BAP)、抗酒石酸酸性磷酸酶5b(TRACP-5b)、25羟基维生素D(25-OH-VD)及临床钙磷代谢指标的相关性,另外还利用多元逐步线性回归分析进一步探讨FGF23含量的影响因素。研究结果:ELISA检测结果显示随着CKD患者肾功能的恶化,FGF23的含量逐渐上升,Klotho蛋白水平降低,并且从CKD3-4期开始,FGF23与Klotho蛋白的含量较前期的差异具有统计学意义(P0.05)。CKD5期患者与CKD1-4期相比,BAP、TRACP-5b含量明显升高,25-OH-VD含量降低,水平的差异均有统计学意义(P0.05);各组Pearson相关分析显示FGF23与BAP、TRACP-5b、碱性磷酸酶、血P、Scr、胱抑素C、尿素氮等指标呈正相关(P0.05),与Klotho蛋白、血钙、25-OH-VD呈负相关(P0.05),与血白蛋白无显著性相关(P0.05)。另外多元逐步线性回归方程显示血磷、Scr是FGF23的独立影响因素。研究结论:FGF23与慢性肾脏病非透析患者肾功能及矿物质代谢紊乱的进展紧密相关,并且可能是CKD患者骨代谢紊乱及肾功能损害病程进展的独立危险因子。
[Abstract]:Objective: with the progress of human society and improve the quality of life, all kinds of disease prone also can not be neglected problems in people's life. The survey data from around the world, there is a kind of disease with an increasing incidence, now has become a public health problem should be paid attention to. It is a chronic kidney disease (CKD). According to reports, China is one of the countries with a high incidence of CKD, data show that adult groups in China every 10 people have 1 people suffering from chronic kidney disease prevention and control, the task is very heavy. In patients with CKD renal function decline in the process, and the abnormal metabolism of calcium and phosphorus bone metabolism is one of the most common complications, significantly increased the mortality rate of CKD patients, and seriously affect the quality of life of the patients. Fibroblast growth factor 23 (FGF23) is a newly discovered in the regulation of calcium and phosphorus metabolism plays an important role With the factor, studies have pointed out that FGF23 is involved in the metabolism of chronic kidney disease mineral anomaly, and can predict the progression of CKD and prognosis of.FGF23 were found to have significant research on disorders of calcium and phosphorus metabolism in patients with CKD, but there are still many mechanism is not completely clear, past studies have some inconsistent therefore, the need for further research. The aim of this retrospective study, the content difference in the different periods of CKD in non dialysis patients with FGF23 detection, to further discuss the relationship between the renal function and mineral metabolism, to provide new ideas for the regulation and clinical prevention and treatment of CKD-MBD. Methods: according to strict diagnostic criteria CKD, in the period from June 2015 to June 2016 to the second hospital of Shandong University Department of Nephrology hospital, selected non dialysis patients with chronic kidney disease in 107 cases Study on 107 people. Also included in the study to exclude malignant tumor, fracture, primary bone metabolic diseases, primary disease parathyroid disease patients. Calculation of glomerular filtration rate, according to the CKD staging criteria for 107 cases of patients were divided into three groups: CKD1-2 period, CKD3-4 period, CKD5 period, the number of cases respectively. In 32 cases, 40 cases, 43 cases. All patients were collected fasting venous blood, using ELISA kit for serum FGF23 detection, Klotho, 25 hydroxy vitamin D (25-OH-VD), bone alkaline phosphatase (BAP), tartrate resistant acid phosphatase 5b (TRACP-5b) content, and statistics were the basic clinical data (age, general condition and conventional medicine) and biochemical parameters (serum calcium, serum phosphorus, creatinine, Cystatin C, urea nitrogen, uric acid, serum albumin, PTH, alkaline phosphatase). The difference of these indexes of patients were compared, and the application of Pearson correlation analysis between FGF23 and bone alkaline phosphatase (BAP), tartrate resistant Acid phosphatase 5b (TRACP-5b), 25 hydroxy vitamin D (25-OH-VD) and the clinical correlation between calcium and phosphorus metabolism index and influencing factors in addition to using stepwise multiple linear regression analysis to further explore the content of FGF23. Results: ELISA showed that with the deterioration of renal function in patients with CKD, FGF23 content increased, the protein level of Klotho from the beginning of the CKD3-4 period decreased, and the difference was statistically significant, the content of FGF23 and Klotho protein compared with previous (P0.05) compared to.CKD5 patients with CKD1-4 stage BAP, TRACP-5b were significantly increased, 25-OH-VD content decreased, the differences were statistically significant (P0.05); group Pearson correlation analysis showed that FGF23 and BAP, TRACP-5b. Alkaline phosphatase, blood P, Scr, Cystatin C, blood urea nitrogen were positively correlated (P0.05), serum calcium and Klotho protein, and negatively correlated with 25-OH-VD (P0.05), and serum albumin had no significant correlation (P 0.05). The multivariate linear regression equation showed that blood phosphorus and Scr were independent factors of FGF23. Conclusion: FGF23 and progression of chronic kidney disease in patients with renal dialysis and mineral metabolism disorders are closely related, and possibly CKD metabolism and renal function in patients with bone damage independent risk factor for progression.

【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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