發(fā)布時間：2018-02-04 16:26

  本文關(guān)鍵詞： 慢性腎臟病 FGF23 骨代謝　出處：《山東大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：研究目的:隨著人類社會的進步以及生活質(zhì)量的提高,各種疾病的多發(fā)也成為困擾人們生活的不可忽視的問題。目前從全世界范圍內(nèi)的調(diào)查數(shù)據(jù)來看,有一種疾病的發(fā)病率越來越高,現(xiàn)在已經(jīng)成為不得不重視的公共衛(wèi)生問題,那就是慢性腎臟病(CKD)。根據(jù)文獻報道,中國是CKD的高發(fā)國家之一,數(shù)據(jù)顯示我國成年人群體中每10人中就有1人患慢性腎臟病,防治任務(wù)相當(dāng)繁重。在CKD患者腎功能進行性下降的過程中,鈣磷代謝和骨代謝異常是最常見的并發(fā)癥之一,顯著提高了 CKD患者的致死率,嚴(yán)重影響了患者的生存質(zhì)量。成纖維生長因子23(FGF23)是新近發(fā)現(xiàn)的在鈣磷代謝的調(diào)節(jié)方面起到重要作用的因子,已有研究指出FGF23參與了慢性腎臟病礦物質(zhì)異常的代謝過程,并且能夠預(yù)測CKD病程進展與預(yù)后。FGF23的發(fā)現(xiàn)對CKD患者鈣磷代謝紊亂的研究有重大的意義,然而目前尚有很多作用機制尚不完全明確,過往研究中也有一些不一致的地方,因此需要進一步研究。本課題擬通過回顧性研究,檢測FGF23在不同時期CKD非透析患者體內(nèi)的含量差異,進一步討論其與腎功能及礦物質(zhì)代謝之間的相關(guān)性,為臨床上CKD-MBD的調(diào)節(jié)及防治提供新的思路。研究方法:嚴(yán)格按照CKD的診斷標(biāo)準(zhǔn),在2015年6月至2016年6月期間來山東大學(xué)第二醫(yī)院腎內(nèi)科住院治療的病人中,篩選出慢性腎臟病非透析患者107例納入研究。另外納入研究的107人排除了惡性腫瘤、骨折、原發(fā)骨代謝疾病、原發(fā)甲狀旁腺疾病等疾病。計算入選患者的腎小球濾過率,按CKD的分期標(biāo)準(zhǔn)將107例入選患者分為三組:CKD1-2期、CKD3-4期、CKD5期,病例數(shù)量分別為32例、40例、43例。收集所有患者空腹靜脈血,利用ELISA試劑盒檢患者血清FGF23、Klotho、25羥基維生素D(25-OH-VD)、骨堿性磷酸酶(BAP)、抗酒石酸酸性磷酸酶5b(TRACP-5b)含量,并統(tǒng)計患者基本臨床資料(年齡、一般情況、常規(guī)用藥)及生化指標(biāo)(血清鈣、血清磷、肌酐、胱抑素C、尿素氮、尿酸、血清白蛋白、PTH、堿性磷酸酶等)。比較各組患者上述指標(biāo)的差異,并應(yīng)用Pearson相關(guān)分析FGF23與骨堿性磷酸酶(BAP)、抗酒石酸酸性磷酸酶5b(TRACP-5b)、25羥基維生素D(25-OH-VD)及臨床鈣磷代謝指標(biāo)的相關(guān)性,另外還利用多元逐步線性回歸分析進一步探討FGF23含量的影響因素。研究結(jié)果:ELISA檢測結(jié)果顯示隨著CKD患者腎功能的惡化,FGF23的含量逐漸上升,Klotho蛋白水平降低,并且從CKD3-4期開始,FGF23與Klotho蛋白的含量較前期的差異具有統(tǒng)計學(xué)意義(P0.05)。CKD5期患者與CKD1-4期相比,BAP、TRACP-5b含量明顯升高,25-OH-VD含量降低,水平的差異均有統(tǒng)計學(xué)意義(P0.05);各組Pearson相關(guān)分析顯示FGF23與BAP、TRACP-5b、堿性磷酸酶、血P、Scr、胱抑素C、尿素氮等指標(biāo)呈正相關(guān)(P0.05),與Klotho蛋白、血鈣、25-OH-VD呈負相關(guān)(P0.05),與血白蛋白無顯著性相關(guān)(P0.05)。另外多元逐步線性回歸方程顯示血磷、Scr是FGF23的獨立影響因素。研究結(jié)論:FGF23與慢性腎臟病非透析患者腎功能及礦物質(zhì)代謝紊亂的進展緊密相關(guān),并且可能是CKD患者骨代謝紊亂及腎功能損害病程進展的獨立危險因子。
[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.

【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R692

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