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慢性腎衰竭患者唾液中胱抑素C及β2微球蛋白的變化及其意義

發(fā)布時(shí)間:2018-05-19 21:14

  本文選題:慢性腎衰竭 + 腎功能檢查; 參考:《河北醫(yī)科大學(xué)》2014年碩士論文


【摘要】:目的:慢性腎衰竭(Chronic Renal Failure,CRF)是由慢性腎臟病引起的腎小球?yàn)V過率(GFR)下降及與此相關(guān)的水電解質(zhì)、代謝廢物的代謝紊亂和相關(guān)臨床各系統(tǒng)癥狀組成的綜合征。慢性腎臟。–KD)是指腎損害≥3個(gè)月,腎損害指腎臟結(jié)構(gòu)或功能的異常(包括病理、血液、尿液、影像學(xué)異常)或GFR<60ml/(min·1.73m2)持續(xù)3個(gè)月以上。慢性腎衰竭近年來流行病學(xué)特點(diǎn)呈現(xiàn)患病率和病死率高的特點(diǎn),同時(shí)大多伴有心腦血管合并癥,心梗腦梗事件頻發(fā),往往死于心腦血管不良事件發(fā)生。目前大多數(shù)慢性腎衰竭都無法得到徹底根治只能延緩腎衰竭的進(jìn)展,大量研究結(jié)果證明早期發(fā)現(xiàn)高血壓并合理降壓、及早發(fā)現(xiàn)尿蛋白異常、干預(yù)治療貧血、調(diào)節(jié)鈣磷代謝及防治腎性骨病,都可以大大延緩腎臟生理功能的損害。慢性腎衰竭的早期發(fā)現(xiàn)、診斷、檢測和防治已成為全球性的公共衛(wèi)生事件,值得關(guān)注。 腎小球?yàn)V過濾率(GFR)是腎功能最好最直接的評價(jià),腎小球?yàn)V過率在慢性腎臟病早期診斷、疾病分期等方面具有重大意義。目前根據(jù)腎臟病患者生存質(zhì)量指導(dǎo)(K/DOQI)指南推薦,廣泛應(yīng)用胱抑素C(CYSC)是近年來反映GFR的新指標(biāo)。它在體內(nèi)有核細(xì)胞以恒定速率產(chǎn)生,可自由經(jīng)腎小球?yàn)V過,且存在與各種體液中,由近曲腎小管重吸收并迅速分解代謝,即便是在炎癥狀態(tài)(如急性反應(yīng)期)和肌肉含量不同情況下,它的產(chǎn)生也不會(huì)改變。胱抑素C是一種簡便、精確、敏感地反映GFR的內(nèi)源性標(biāo)志物,能較早地發(fā)現(xiàn)腎臟濾過功能受損,為臨床早期診斷腎損害提供依據(jù)。當(dāng)腎小球的濾過輕微發(fā)生損傷,血清胱抑素C含量的增加就可以發(fā)生,并隨著病情的加重含量逐漸增加。β2微球蛋白(β-2MG)是機(jī)體產(chǎn)生內(nèi)源性低分子量血清蛋白質(zhì),遍及于血漿、尿液等體液中,其含量極微,但卻非常恒定。因?yàn)棣?微球蛋白在體內(nèi)以速率恒定產(chǎn)生,年齡、性別、機(jī)體肌肉組織含量多少等因素不會(huì)影響其血漿中的含量,而且β2微球蛋白相對分子量小,可自由通過腎小球,且僅有腎臟排泄,所以測定血漿中β2微球蛋白水平比檢測血清肌酐水平用于評價(jià)腎功能更加靈敏,腎小球?yàn)V過功能受損血漿中β2微球蛋白水平升高。胱抑素C和β2微球蛋白均是早期診斷CKD敏感、準(zhǔn)確的指標(biāo),較傳統(tǒng)的血肌酐(Scr)更敏感、更可靠。 唾液作為人體重要的外分泌液之一,其中蘊(yùn)含著豐富的生物學(xué)信息。研究發(fā)現(xiàn)唾液中的某些成分會(huì)發(fā)生變化時(shí)會(huì)提示機(jī)體發(fā)生某種疾病。唾液標(biāo)本采集可作為無創(chuàng)性檢測的主要標(biāo)本來源,它具有簡便、快速、經(jīng)濟(jì)、貯存與攜帶方便和無創(chuàng)性等特點(diǎn)。目前已在在眾多疾病的診斷、檢測、治療、預(yù)后中具有廣闊前景,,近年來有研究報(bào)道:唾液與血清尿素氮、肌酐有顯著相關(guān)性,這表明唾液中尿素氮、肌酐的檢測數(shù)據(jù)可以作為評價(jià)腎功能的指標(biāo)應(yīng)用于臨床。胱抑素C及β2微球蛋白作為新興的腎功能檢測靈敏項(xiàng)目,它們在唾液中的含量改變及相關(guān)性還未曾被發(fā)現(xiàn)。 方法:本實(shí)驗(yàn)通過收集河北醫(yī)科大學(xué)第二醫(yī)院腎內(nèi)科已確診為慢性腎衰竭患者122例,記錄基本資料:性別、年齡、疾病名稱、血清肌酐、治療方式。依據(jù)CKD-EPI公式計(jì)算估計(jì)的腎小球?yàn)V過率(eGFR)后將慢性腎衰竭患者設(shè)為3組。選用胱抑素C和β2微球蛋白試劑盒,采用免疫比濁檢測方法,應(yīng)用COBAS8000型全自動(dòng)生化免疫分析儀測定數(shù)值,檢測各組慢性腎衰竭患者唾液與血清中Cysc、β2MG的含量水平及相關(guān)性。 結(jié)果: 1122例慢性腎衰竭患者的研究實(shí)驗(yàn),54例(44%)腎功能正常患者,52例(42%)腎功能不全患者和16例(14%)腎衰竭患者。引起慢性腎功能衰竭疾病原因從高到底分別是:慢性腎炎(36例)、膜性腎。18例)、慢性腎衰竭(14例)、系統(tǒng)性紅斑狼瘡腎損害(10例)、乙肝相關(guān)性膜性腎。8例)、高血壓腎損害、糖尿病腎病、紫癜性腎炎(均為7例)、局灶階段性腎小球硬化(5例)、慢性間質(zhì)性腎炎、妊高癥腎損害、原發(fā)性或繼發(fā)性淀粉樣變、膜增生性腎小球腎炎、小血管炎腎損害(均為2例)。所有患者均未進(jìn)行血液透析治療而使用藥物和飲食控制治療。 2腎功能正常組、腎功能不全組、腎衰竭組血清肌酐含量分別為(61.29±13.23)、(154.84±84.69)、(497.75±154.11);eGFR分別為(117.17±16.87)、(54.41±26.87)、(9.10±2.93) 3Cysc在唾液與血清的含量:結(jié)果顯示腎功能正常組、腎功能下降組、腎衰竭組唾液中的含量分別為(0.66±0.13)、(0.97±0.10)、(1.31±0.09),血清中的含量分別為(0.73±0.12)、(1.32±0.44)、(2.65±0.75) 2β2MG在唾液與血清的含量:結(jié)果顯示腎功能正常組、腎功能下降組、腎衰竭組唾液中的含量分別為(0.20±0.08)、(0.23±0.11)、(0.40±0.12),血清中的含量分別為(1.48±0.15)、(2.61±0.84)、(8.51±1.84) 3慢性腎衰竭患者唾液中與血清中Cysc含量的相關(guān)性:Pearson相關(guān)分析顯示,腎功能正常組、腎功能下降組、腎衰竭組患者Cysc含量和血清中Cysc含量呈顯著正相關(guān)(r腎功能正常組=0.958、p=0.000)、(r腎功能下降組=0.231、p=0.099)、(r腎衰竭組=0.953、p=0.000) 4慢性腎衰竭患者唾液中與血清中β2MG含量的相關(guān)性:Pearson相關(guān)分析顯示,腎功能正常組、腎功能下降組、腎衰竭組患者β2MG含量和血清中β2MG含量呈正相關(guān)(r腎功能正常組=0.951、p=0.000)、(r腎功能下降組=0.696、p=0.000)、(r腎衰竭組=0.960、p=0.000) 結(jié)論: 1慢性腎衰竭患者唾液Cysc濃度隨血清Cysc濃度的升高而升高。 2慢性腎衰竭患者唾液β2MG濃度隨血清β2MG的升高而升高。 3慢性腎衰竭患者唾液Cysc濃度與血清Cysc濃度呈正相關(guān)。 4慢性腎衰竭患者唾液β2MG濃度與血清β2MG濃度呈正相關(guān)。 5唾液CysC、β2MG的測定方便可行,可用作無創(chuàng)性腎功能檢測方法,在臨床上具有一定的實(shí)用價(jià)值,值得推廣應(yīng)用于臨床慢性腎衰竭患者早期和終末期腎功能的評價(jià)領(lǐng)域,為唾液檢測開辟新的篇章。
[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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