血清Klotho和FGF-23与慢性肾脏病患者矿物质代谢及心脏结构的关系

发布时间：2018-03-10 22:36

  本文选题：Klotho　切入点：成纤维细胞生长因子-23　出处：《大连医科大学》2014年硕士论文　论文类型：学位论文

【摘要】：目的：通过酶联免疫吸附试验（enzyme-linked immunosorbent assay，ELISA）检测慢性肾脏病（chronic kidney disease，CKD）患者不同肾功能阶段血清Klotho和成纤维细胞生长因子23（fibroblast growth factor23，，FGF-23）水平的变化，探讨其与矿物质代谢及心脏结构的关系。 方法：选取2013年7月至2014年1月在大连医科大学附属第二医院肾内科住院的CKD患者，共75例。排除标准：严重的感染、肝胆疾病、活动性消耗性疾病（如恶性肿瘤或肺结核）；急性心肌梗死、心力衰竭、急性脑血管疾病；原发性甲状旁腺疾病、甲状旁腺切除、肾移植术后患者。另选取同期在本院体检的健康查体者作为对照组，共13例。根据肾小球滤过率（estimated glomerular filtrationrate，eGRF）将CKD患者分为：CKD2期12例、CKD3期14例、CKD4期12例、CKD5期37例（其中包括非透析组21例、血透组10例和腹透组6例）。又根据左心室肥厚（left ventricular hypertrophy，LVH）诊断标准（左心室心肌质量指数[leftventricular mass index，LVMI]，男性≥135g/m2、女性≥110g/m2）将CKD2-5期非透析患者分为LVH组14例和非LVH组45例。收集所有研究对象的一般临床资料，包括性别、年龄、体重指数、原发疾病等；应用自动分析仪检测血红蛋白、血清白蛋白、甘油三酯、胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、血清肌酐、血钙、血磷；应用免疫化学荧光法检测全段甲状旁腺激素（intact parathyroidhormone，iPTH）；根据MDRD公式计算eGRF，并计算校正钙、钙磷乘积。应用ELISA法检测血清Klotho和FGF-23浓度。彩色多普勒超声测定左心室后壁厚度、室间隔厚度、左心室舒张末期内径，计算LVMI。采用SPSS13.0统计学软件进行统计分析和处理，P0.05为差异具有统计学意义。另外，应用局部加权回归散点平滑法（locally weighted scatter plot smoothing，LOESS）观察血清Klotho、FGF-23与eGRF的关系。 结果： 1. CKD2-5期患者（非透析），血清Klotho水平均低于对照组（P＜0.05）。CKD4期、CKD5期血清Klotho水平均低于CKD2期、CKD3期（P＜0.05）。CKD3-5期血清FGF-23水平均高于对照组（P＜0.05）。CKD4期血清FGF-23水平高于CKD2期、CKD3期（P＜0.05）。CKD5期血清FGF-23水平高于CKD2-4期（P＜0.05）。CKD2-5期血钙水平相近（P＞0.05）。CKD2期、CKD3期血磷较对照组略低（P＞0.05）。血清iPTH、血磷和钙磷乘积仅在对照组和CKD5期之间存在显著性差异。相关性分析显示，血清Klotho与血清FGF-23（r=-0.524，P＜0.01）、血磷（r=-0.486，P＜0.01）、钙磷乘积（r=-0.494，P＜0.01）、iPTH（r=-0.466，P＜0.01）均呈负相关。在校正年龄、性别及eGFR后，血清Klotho仍与年龄、eGFR独立相关。血清FGF-23与血磷（r=0.658，P＜0.01）、钙磷乘积（r=0.638，P＜0.01）、iPTH（r=0.603，P＜0.01）均呈正相关。 2. CKD5期血透组、腹透组和非透析组的患者中，非透析组血清Klotho水平高于血透组、腹透组（P＜0.05），血清FGF-23水平与血透组、腹透组无显著性差异，血清iPTH低于血透组（P＜0.01）、高于腹透组（P＞0.05）。血透组血清Klotho水平低于腹透组（P＞0.05），而血清iPTH明显高于腹透组（P＜0.05）。 3.应用LOESS观察CKD2-5期患者（非透析）血清Klotho、FGF-23、iPTH、血钙、磷与eGFR的关系，发现血清Klotho与eGFR呈线性相关，eGFR每下降1ml/min，血清Klotho下降4.79pg/ml（95%CI3.73-5.86pg/ml，P＜0.01）。校正年龄后，eGFR每下降1ml/min，血清Klotho下降4.75pg/ml（95%CI3.83-5.66pg/ml，P＜0.01）。血清FGF-23、iPTH、血磷均与eGFR呈非线性相关。血清FGF-23在CKD2期、iPTH和血磷在CKD2-3期变化不大，后随eGFR下降而急剧上升。FGF-23在eGFR下降至50ml/min时迅速升高，而血iPTH在eGFR下降至27ml/min时、血磷在eGFR下降至26ml/min时急剧升高。 4. CKD2-5期患者（非透析）中，LVH组体重指数、血红蛋白、低密度脂蛋白胆固醇、FGF-23均高于非LVH组（P0.05），而血清Klotho明显低于非LVH组（P0.01）。LVMI与FGF-23呈正相关（r=0.313，P＜0.01），LVMI与Klotho呈负相关（r=-0.283，P＜0.01）。进一步行多因素Logistic回归分析显示，血清Klotho（OR=0.995，P＜0.01）和血清FGF-23（OR=1.002，P＜0.05）均为CKD患者LVH发生的相关因素。 结论： 1.慢性肾脏病非透析患者血清FGF-23的升高早于血磷和血甲状旁腺激素的增高，而血清Klotho的下降先于血清FGF-23的升高，故Klotho可能是慢性肾脏病矿物质代谢紊乱的早期生物标志物。 2. Klotho、FGF-23可能是慢性肾脏病非透析患者左心室肥厚的影响因素，Klotho是保护性因素，而FGF-23是独立危险因素。
[Abstract]:Objective: by enzyme-linked immunosorbent assay (enzyme-linked immunosorbent, assay, ELISA) detection of chronic kidney disease (chronic kidney, disease, CKD) in patients with different renal function stage serum Klotho and fibroblast growth factor 23 (fibroblast growth, Factor23, FGF-23) level changes, discuss the relationship between the mineral metabolism and cardiac structure.
Methods: from July 2013 to January 2014 on renal function in patients with CKD hospitalized in Second Affiliated Hospital of Dalian Medical University, a total of 75 cases of hepatobiliary disease. Exclusion criteria: severe infection, active wasting diseases (such as cancer or tuberculosis); acute myocardial infarction, heart failure, acute cerebral vascular disease; primary parathyroid diseases, parathyroidectomy, patients after renal transplantation were selected in our hospital. The other healthy subjects served as control group, 13 cases in total. According to glomerular filtration rate (estimated, glomerular filtrationrate, eGRF) CKD patients were divided into 12 cases of stage CKD2, stage CKD3 14 cases, CKD4 12 cases, stage CKD5 in 37 cases (including 21 cases of non dialysis patients, hemodialysis and peritoneal dialysis group and 10 cases in group 6 cases). According to the left ventricular hypertrophy (left ventricular, hypertrophy, LVH) diagnostic criteria (left ventricular mass index [LEFTVENTRICULAR mass index, LVMI], The male is more than 135g/m2, 110g/m2 or CKD2-5) female non dialysis patients were randomly divided into LVH group of 14 cases and 45 cases in non LVH group. The clinical data were collected from all participants, including gender, age, body mass index, primary disease detection; application of automatic analyzer hemoglobin, serum albumin, triglyceride, cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, serum creatinine, blood calcium, blood phosphorus; detection of parathyroid hormone by immunohistochemistry fluorescence method (intact parathyroidhormone, iPTH); eGRF was calculated according to MDRD formula, and calculate the corrected calcium, calcium and phosphorus product. ELISA method was used to detect the serum Klotho and FGF-23 concentration. The color Doppler ultrasound of left ventricle determination of posterior wall thickness, interventricular septum thickness, left ventricular end diastolic diameter, calculation of LVMI. using SPSS13.0 statistical software for statistical analysis and processing, P0.05 differed significantly In addition, locally weighted scatter plot smoothing (LOESS) was used to observe the relationship between serum Klotho, FGF-23 and eGRF.
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