慢性肾衰竭患者唾液中胱抑素C及β2微球蛋白的变化及其意义

发布时间：2018-05-19 21:14

  本文选题：慢性肾衰竭 + 肾功能检查　； 参考：《河北医科大学》2014年硕士论文

【摘要】：目的：慢性肾衰竭（Chronic Renal Failure，CRF）是由慢性肾脏病引起的肾小球滤过率（GFR)下降及与此相关的水电解质、代谢废物的代谢紊乱和相关临床各系统症状组成的综合征。慢性肾脏病（CKD）是指肾损害≥3个月，肾损害指肾脏结构或功能的异常（包括病理、血液、尿液、影像学异常）或GFR＜60ml/（min·1.73m2）持续3个月以上。慢性肾衰竭近年来流行病学特点呈现患病率和病死率高的特点，同时大多伴有心脑血管合并症，心梗脑梗事件频发，往往死于心脑血管不良事件发生。目前大多数慢性肾衰竭都无法得到彻底根治只能延缓肾衰竭的进展，大量研究结果证明早期发现高血压并合理降压、及早发现尿蛋白异常、干预治疗贫血、调节钙磷代谢及防治肾性骨病，都可以大大延缓肾脏生理功能的损害。慢性肾衰竭的早期发现、诊断、检测和防治已成为全球性的公共卫生事件，值得关注。 肾小球滤过滤率（GFR）是肾功能最好最直接的评价，肾小球滤过率在慢性肾脏病早期诊断、疾病分期等方面具有重大意义。目前根据肾脏病患者生存质量指导（K/DOQI）指南推荐，广泛应用胱抑素C（CYSC）是近年来反映GFR的新指标。它在体内有核细胞以恒定速率产生，可自由经肾小球滤过，且存在与各种体液中，由近曲肾小管重吸收并迅速分解代谢，即便是在炎症状态（如急性反应期）和肌肉含量不同情况下，它的产生也不会改变。胱抑素C是一种简便、精确、敏感地反映GFR的内源性标志物，能较早地发现肾脏滤过功能受损，为临床早期诊断肾损害提供依据。当肾小球的滤过轻微发生损伤，血清胱抑素C含量的增加就可以发生，并随着病情的加重含量逐渐增加。β2微球蛋白（β-2MG）是机体产生内源性低分子量血清蛋白质，遍及于血浆、尿液等体液中，其含量极微，但却非常恒定。因为β2微球蛋白在体内以速率恒定产生，年龄、性别、机体肌肉组织含量多少等因素不会影响其血浆中的含量，而且β2微球蛋白相对分子量小，可自由通过肾小球，且仅有肾脏排泄，所以测定血浆中β2微球蛋白水平比检测血清肌酐水平用于评价肾功能更加灵敏，肾小球滤过功能受损血浆中β2微球蛋白水平升高。胱抑素C和β2微球蛋白均是早期诊断CKD敏感、准确的指标，较传统的血肌酐（Scr）更敏感、更可靠。 唾液作为人体重要的外分泌液之一，其中蕴含着丰富的生物学信息。研究发现唾液中的某些成分会发生变化时会提示机体发生某种疾病。唾液标本采集可作为无创性检测的主要标本来源，它具有简便、快速、经济、贮存与携带方便和无创性等特点。目前已在在众多疾病的诊断、检测、治疗、预后中具有广阔前景，，近年来有研究报道：唾液与血清尿素氮、肌酐有显著相关性，这表明唾液中尿素氮、肌酐的检测数据可以作为评价肾功能的指标应用于临床。胱抑素C及β2微球蛋白作为新兴的肾功能检测灵敏项目，它们在唾液中的含量改变及相关性还未曾被发现。 方法：本实验通过收集河北医科大学第二医院肾内科已确诊为慢性肾衰竭患者122例，记录基本资料：性别、年龄、疾病名称、血清肌酐、治疗方式。依据CKD-EPI公式计算估计的肾小球滤过率（eGFR）后将慢性肾衰竭患者设为3组。选用胱抑素C和β2微球蛋白试剂盒，采用免疫比浊检测方法，应用COBAS8000型全自动生化免疫分析仪测定数值，检测各组慢性肾衰竭患者唾液与血清中Cysc、β2MG的含量水平及相关性。 结果： 1122例慢性肾衰竭患者的研究实验，54例（44%）肾功能正常患者，52例（42%）肾功能不全患者和16例（14%）肾衰竭患者。引起慢性肾功能衰竭疾病原因从高到底分别是：慢性肾炎（36例）、膜性肾病（18例）、慢性肾衰竭（14例）、系统性红斑狼疮肾损害（10例）、乙肝相关性膜性肾病（8例）、高血压肾损害、糖尿病肾病、紫癜性肾炎（均为7例）、局灶阶段性肾小球硬化（5例）、慢性间质性肾炎、妊高症肾损害、原发性或继发性淀粉样变、膜增生性肾小球肾炎、小血管炎肾损害（均为2例）。所有患者均未进行血液透析治疗而使用药物和饮食控制治疗。 2肾功能正常组、肾功能不全组、肾衰竭组血清肌酐含量分别为（61.29±13.23）、（154.84±84.69）、（497.75±154.11）；eGFR分别为（117.17±16.87）、（54.41±26.87）、（9.10±2.93） 3Cysc在唾液与血清的含量：结果显示肾功能正常组、肾功能下降组、肾衰竭组唾液中的含量分别为（0.66±0.13）、（0.97±0.10）、（1.31±0.09），血清中的含量分别为（0.73±0.12）、（1.32±0.44）、（2.65±0.75） 2β2MG在唾液与血清的含量：结果显示肾功能正常组、肾功能下降组、肾衰竭组唾液中的含量分别为（0.20±0.08）、（0.23±0.11）、（0.40±0.12），血清中的含量分别为（1.48±0.15）、（2.61±0.84）、（8.51±1.84） 3慢性肾衰竭患者唾液中与血清中Cysc含量的相关性：Pearson相关分析显示，肾功能正常组、肾功能下降组、肾衰竭组患者Cysc含量和血清中Cysc含量呈显著正相关(r肾功能正常组=0.958、p=0.000）、（r肾功能下降组=0.231、p=0.099）、（r肾衰竭组=0.953、p=0.000） 4慢性肾衰竭患者唾液中与血清中β2MG含量的相关性：Pearson相关分析显示，肾功能正常组、肾功能下降组、肾衰竭组患者β2MG含量和血清中β2MG含量呈正相关(r肾功能正常组=0.951、p=0.000）、（r肾功能下降组=0.696、p=0.000）、（r肾衰竭组=0.960、p=0.000） 结论： 1慢性肾衰竭患者唾液Cysc浓度随血清Cysc浓度的升高而升高。 2慢性肾衰竭患者唾液β2MG浓度随血清β2MG的升高而升高。 3慢性肾衰竭患者唾液Cysc浓度与血清Cysc浓度呈正相关。 4慢性肾衰竭患者唾液β2MG浓度与血清β2MG浓度呈正相关。 5唾液CysC、β2MG的测定方便可行，可用作无创性肾功能检测方法，在临床上具有一定的实用价值，值得推广应用于临床慢性肾衰竭患者早期和终末期肾功能的评价领域，为唾液检测开辟新的篇章。
[Abstract]:Objective: Chronic Renal Failure (CRF) is a syndrome of the decrease of glomerular filtration rate (GFR) caused by chronic renal disease and related water and electrolytes, metabolic disorders of metabolic waste and the syndrome associated with various clinical systems. Chronic renal disease (CKD) refers to renal damage more than 3 months and renal damage refers to the structure or function of the kidney. Abnormality (including pathology, blood, urine, imaging abnormalities) or GFR < 60ml/ (min. 1.73m2) lasted for more than 3 months. The epidemiological characteristics of chronic renal failure are characterized by high morbidity and mortality in recent years, most of which are accompanied by cardio cerebral vascular complication, frequent occurrence of myocardial infarction and often death from cardiovascular and cerebrovascular events. A number of chronic renal failure can not be completely eradicated to delay the progress of renal failure. A large number of research results have proved that early detection of hypertension and reasonable hypotension, early detection of urinary protein abnormalities, intervention in the treatment of anemia, the regulation of calcium and phosphorus metabolism and the prevention and treatment of renal osteopathy can greatly delay the impairment of kidney physiological function. It is found that diagnosis, detection and prevention have become a global public health event and deserve our attention.
Glomerular filtration filtration rate (GFR) is the best and most direct evaluation of renal function. Glomerular filtration rate is of great significance in the early diagnosis of chronic kidney disease and disease staging. Currently, Cystatin C (CYSC) is widely used as a new indicator of GFR in recent years according to the guidelines for the quality of life of patients with kidney disease (K/DOQI). It has a nucleation in the body. The cells are produced at a constant rate and are free of glomerular filtration and exist in various body fluids, reabsorbed by the proximal renal tubules and rapidly decompose metabolism, even in the inflammatory state (such as acute reaction period) and muscle content, and its production will not change. Cystatin C is a simple, accurate and sensitive reflection of endogenous GFR. Biomarkers can be found early on impaired renal filtration function and provide a basis for early diagnosis of renal damage. When glomerular filtration is slightly damaged, the increase of serum cystatin C content can occur and increases with the aggravation of the disease. Beta 2 microglobulin (beta -2MG) is the body producing endogenous low molecular weight serum protein The content of the plasma, urine and other body fluids is very small, but it is very constant, but it is very constant. Because the beta 2 microglobulin is produced at a constant rate in the body, the age, sex, the muscle tissue content of the body does not affect the content of the plasma, and the beta 2 microglobulin is small in the molecular weight, and can be freely passed through the glomerulus, and only the kidney excreted. Therefore, the level of beta 2 microglobulin in plasma is more sensitive than the serum creatinine level for evaluating renal function. The level of beta 2 microglobulin in plasma damaged glomerular filtration function is higher. Cystatin C and beta 2 microglobulin are both sensitive and accurate in early diagnosis of CKD, more sensitive and more reliable than that of serum creatinine (Scr).
Saliva, one of the most important exocrine fluids in the human body, contains abundant biological information. It is found that some components in the saliva may indicate a certain disease in the body. The collection of saliva specimen can be used as the main source of noninvasive testing, which has a convenient, rapid, economical, convenient and noninvasive storage. It has been widely used in the diagnosis, detection, treatment and prognosis of many diseases. In recent years, it has been reported that there is a significant correlation between saliva and serum urea nitrogen and creatinine. This indicates that the detection data of urea nitrogen and creatinine in saliva can be used as a marker for the evaluation of renal function in clinical. Cystatin C and beta 2 microglobulin As a sensitive item in the detection of renal function, the change and correlation of their contents in saliva have not been found.
Methods: 122 patients with chronic renal failure in the nephrology department of the second hospital of Hebei Medical University were collected. The basic data were recorded: sex, age, disease name, serum creatinine, method of treatment. After calculating the estimated glomerular filtration rate (eGFR) according to the CKD-EPI formula, the patients with chronic renal failure were set up in 3 groups. Cystatin C was selected. Beta 2 microglobulin kit was used to determine the level and correlation of Cysc, beta 2MG in saliva and serum of patients with chronic renal failure by using immunoturbidimetry and using COBAS8000 automatic biochemical immunoanalyzer.
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