维持性血液透析患者血清FGF-23水平和血管钙化关系的研究
发布时间：2018-07-23 20:46
【摘要】：背景目前全球慢性肾脏病(CKD)发病率及发病数量呈明显增多趋势,据统计全球每年约有10%-13%的人群发病,其中约1%的患者发展至CKD5期。我国每年约有1万人进入透析阶段。钙磷代谢紊乱和心血管疾病并发症足维持性血液透析患者的严重的并发症,也是影响患者生活质量和生存率的主要因素。许多证据表明,尿毒症患者长期钙磷代谢紊乱可引起继发性甲状旁腺功能亢进、矿物质和骨代谢异常、转移性钙化,包括心肌、肺、心脏瓣膜及血管等。以上因素均与慢性肾功能衰竭的死亡率增加相关联,其中心血管并发症是导致血液透析患者死亡的首要原因。研究发现,血管钙化是发生心血管事件的主要原因。而血液透析患者发生血管钙化的机制比较复杂,有多种危险因素参与,除了传统的心血管危险因素如高龄、男性、吸烟史、高血压、糖尿病、高脂血症等外,近年的大量研究发现血管钙化的中心环节是慢性炎症和动脉粥样硬化。而动脉粥样硬化与钙磷代谢紊乱、营养不良、慢性炎症等因素有关。 成纤维细胞生长因子(Fibroblast growth factor-23, FGF-23),是一种新型的钙磷和维生素D调节因子,在维持性血液透析患者的外周血中显著增高,是血液透析患者血管钙化的独立危险因素。维持性血液透析患者普遍存在钙磷代谢紊乱和低1,25(OH)2D3,而口服维生素D受体激活剂(骨化三醇)的治疗可能引起FGF-23水平升高,那么是否会加重血管钙化的研究较少。2009年,KDIGO指南中建议采用腹部侧位片联合超声心动图检查来评估血管钙化情况。 目的观察我血液透析中心维持性血液透析患者腹主动脉及心脏瓣膜钙化、颈动脉内膜中层厚度(IMT)增厚的情况,分析引起血管钙化的危险因素,探讨FGF-23水平与血管钙化各危险因素之间的关系及长期口服小剂量维生素D治疗对血管钙化危险因素的作用。 方法选择我中心2013.3—2014.2维持性血液透析的患者63例,健康对照组20例,两组均用双抗夹心酶联ELISA法检测血清成纤维细胞生长因子-23(FGF-23)水平。记录所有血液透析患者一般资料及临床资料,完善相关实验室检查,用全自动生化分析仪检测钙(Ca)、磷(Pi)、碱性磷酸酶(ALP)、白蛋白(ALB)、胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、血糖(Glu)、肌酐(Scr)、血红蛋白(Hb)等,用免疫化学发光法测甲状旁腺素(iPTH),用免疫透射比浊法测铁蛋白(FER)、维生素B12(V-B12)和超敏C-反应蛋白(hsCRP),采用彩色多普勒超声仪检测有无心肌及瓣膜钙化、颈动脉内膜中层厚度(IMT)及有无动脉斑块形成,腰椎侧位X片查腹主动脉钙化情况。统计学处理采用SPSS17.0统计软件包,以P0.05为差异有统计学意义。 结果1、维持性血液透析患者的临床资料：63例患者平均年龄52.5±23.33岁。原发病：慢性肾小球肾炎23例(36.5%),糖尿病肾病25例(39.6%),多囊肾1例(1.6%),高血压肾病11例(17.5%),原因不明3例(4.8%)。其中已口服小剂量骨化三醇治疗3个月以上的患者有33例(占52.38%)。 2、钙化发生情况：63例维持性血液透析患者中无血管钙化的患者33例(无钙化组),有血管钙化的31例(钙化组),其中有11例发生腹主动脉血管钙化,发生率为17.5%；有心脏瓣膜钙化5例(主动脉瓣或和二尖瓣钙化、心肌钙化),发生率为7.9%；颈动脉内膜中层厚度(IMT)大于0.9mm或斑块形成的患者有8例(12.7%)；多处钙化同时存在的患者7例(11.1%)。 钙化组与非钙化组比较,年龄、透析龄、Pi、钙磷乘积、ALB、hsCRP、FGF-23有显著差别,差异有统计学意义,P0.05。骨化三醇治疗组血管钙化率(36.36%)较非骨化三醇治疗组血管钙化率(63.33%)明显降低,差异有统计学意义,P0.05。 3、多因素logistic回归分析血管钙化的危险因素,结果显示：年龄、hsCRP、Pi、FGF-23及未服用骨化三醇可能是发生血管钙化的主要危险因素,高水平的ALB为保护性因素。 4、FGF-23水平与血磷及钙磷乘积成正相关,与ALB、ALP、Ca、hsCRP、年龄、透析龄、iPTH、口服骨化三醇均无明显相关性。 5、骨化三醇治疗组血Ca(2.16±0.20mmol/L)较非骨化三醇治疗组Ca(1.9910.27mmol/L)明显升高,差异有统计学意义,P0.05。骨化三醇治疗组iPTH (33.98±22.39pmol/L)、 ALP (90.29±43.22U/L)、hsCRP (5.40±3.92mg/L)、CaxPi (56.76±13.97mg2/ml2)水平较非骨化三醇治疗组iPTH (52.9±36.49pmol/L)、ALP (128.20±82.14U/L)、hsCRP(9.05±8.34)、 Ca×Pi (49.66±14.62mg2/ml2)明显降低,差异有统计学意义,P0.05。对FGF-23无显著影响。 结论1、血液透析患者血管钙化的危险因素有：年龄、血FGF-23、Pi、hsCRP及未服用骨化三醇,高ALB为保护性因素。 2、小剂量骨化三醇治疗可能导致血钙升高,使iPTH、hsCRP、ALP、Ca×Pi下降,有可能导致血管钙化发生率减低。对FGF-23无显著影响。
[Abstract]:Background the incidence and number of CKD in global chronic kidney disease (CKD) are increasing obviously. According to the statistics, about 1% of the patients have developed to the CKD5 stage. About 10 thousand people enter the dialysis stage each year in China. The disorder of calcium and phosphorus metabolism and the complications of cardiovascular disease are serious in the maintenance hemodialysis patients. The complications are also the main factors affecting the quality of life and survival of patients. Many evidence suggests that chronic metabolic disorders of calcium and phosphorus in uremia patients can cause secondary hyperparathyroidism, abnormal mineral and bone metabolism, metastatic calcification, including myocardium, lung, heart valve and blood vessels. All of these factors are associated with chronic renal failure. Cardiovascular complications are the leading causes of death in hemodialysis patients. Studies have found that vascular calcification is the main cause of cardiovascular events. The mechanism of vascular calcification in hemodialysis patients is complex, with a variety of risk factors involved, with the exception of the traditional cardiovascular risk factors such as high. Age, male, smoking history, hypertension, diabetes, hyperlipidemia and so on. A large number of recent studies have found that the central link of vascular calcification is chronic inflammation and atherosclerosis, and atherosclerosis is associated with disorders of calcium and phosphorus metabolism, malnutrition, chronic inflammation and so on.
Fibroblast growth factor-23 (FGF-23), a new type of calcium phosphorus and vitamin D regulator, is significantly increased in the peripheral blood of maintenance hemodialysis patients. It is an independent risk factor for vascular calcification in hemodialysis patients. There is a widespread disorder of calcium and phosphorus metabolism and low 1,25 (OH) in maintenance hemodialysis patients. 2D3, while the treatment of oral vitamin D receptor activator (ossified three alcohol) may cause a higher level of FGF-23, then the study of whether or not it will aggravate vascular calcification is less.2009 years. The KDIGO guide recommends the use of abdominal side slice combined echocardiography to assess vascular calcification.
Objective To observe the calcification of abdominal aorta and heart valve and the thickness of carotid intima media thickness (IMT) in the maintenance hemodialysis patients at hemodialysis center, to analyze the risk factors of vascular calcification and to explore the relationship between the risk factors of FGF-23 and the risk factors of vascular calcification and the long-term oral dose of vitamin D in the treatment of vascular calcium. The role of the risk factors.
Methods 63 patients with 2013.3 to 2014.2 maintenance hemodialysis and 20 healthy controls were selected. The level of serum fibroblast growth factor -23 (FGF-23) was detected by double anti sandwich ELISA method in the two groups. The general data and clinical data of all hemodialysis patients were recorded, the related laboratory examination was perfected, and the automatic biochemical analysis was used. The apparatus detected calcium (Ca), phosphorus (Pi), alkaline phosphatase (ALP), albumin (ALB), cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), high density lipoprotein (HDL), blood glucose (Glu), creatinine (Scr), hemoglobin (Hb), and so on. Immunochemiluminescence was used to measure the parathyroid hormone (iPTH) and immunoturbidimetry. The hypersensitive C- reactive protein (hsCRP) was used to detect the calcification of the myocardium and valve, the thickness of the carotid artery intima media (IMT) and the atherosclerotic plaque in the carotid artery, and the calcification of the abdominal aorta at the lumbar side of the lumbar vertebra by the color Doppler ultrasound. The statistical treatment was statistically significant with the difference of the SPSS17.0 statistical package. The difference was statistically significant with the difference of P0.05.
Results 1, the clinical data of maintenance hemodialysis patients: the average age of 63 patients was 52.5 + 23.33 years old. The primary disease: 23 cases of chronic glomerulonephritis (36.5%), 25 cases of diabetic nephropathy (39.6%), 1 cases of polycystic kidney (1.6%), 11 cases of hypertensive nephropathy (17.5%), unexplained 3 cases (4.8%). There were 33 cases (52.38%).
2, calcification occurred in 63 cases of maintenance hemodialysis patients without vascular calcification in 33 cases (no calcification group) and 31 cases of vascular calcification (calcification group), of which 11 cases had abdominal aorta calcification, the incidence was 17.5%, 5 cases with cardiac valve calcification (aortic valve or mitral calcification, cardiac calcification), the incidence of 7.9%; neck 7.9%. Eight patients (12.7%) had intima-media thickness (IMT) greater than 0.9 mm or plaque formation, and seven patients (11.1%) had multiple calcifications.
Compared with the non calcification group, age, age, Pi, calcium and phosphorus product, ALB, hsCRP, FGF-23 had significant differences, and the difference was statistically significant. The vascular calcification rate (36.36%) in P0.05. three alcohol treatment group was significantly lower than that of non ossified three alcohol treatment group (63.33%), and the difference was statistically significant, P0.05.
3, the risk factors of vascular calcification were analyzed by multiple factor Logistic regression. The results showed that age, hsCRP, Pi, FGF-23 and not taking ossification three alcohol may be the main risk factors for vascular calcification, and high level ALB is a protective factor.
4. FGF-23 levels were positively correlated with serum phosphorus and calcium-phosphorus product, but not with ALB, ALP, Ca, hsCRP, age, dialysis age, iPTH and oral calcitriol.
5, the blood Ca (2.16 + 0.20mmol/L) in the three group of the ossification group was significantly higher than that in the non ossified three alcohol treatment group. The difference was statistically significant. The P0.05. ossification three alcohol treatment group was iPTH (33.98 + 22.39pmol/L), ALP (90.29 + 43.22U/L), hsCRP (5.40 + 3.92mg/L), and CaxPi (56.76 +) was more than the non ossified three alcohol treatment group (52.9). + 36.49pmol/L), ALP (128.20 + 82.14U/L), hsCRP (9.05 + 8.34), Ca * Pi (49.66 + 14.62mg2/ml2) obviously decreased, the difference was statistically significant, P0.05. had no significant effect on FGF-23.
Conclusion 1. The risk factors of vascular calcification in hemodialysis patients are age, serum FGF-23, Pi, hsCRP and no calcitriol. High ALB is the protective factor.
2, small dose of ossification of three alcohol may lead to a increase in blood calcium and decrease iPTH, hsCRP, ALP, Ca x Pi, which may lead to a decrease in the incidence of vascular calcification. There is no significant effect on FGF-23.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R692.5
本文编号：2140592
[Abstract]:Background the incidence and number of CKD in global chronic kidney disease (CKD) are increasing obviously. According to the statistics, about 1% of the patients have developed to the CKD5 stage. About 10 thousand people enter the dialysis stage each year in China. The disorder of calcium and phosphorus metabolism and the complications of cardiovascular disease are serious in the maintenance hemodialysis patients. The complications are also the main factors affecting the quality of life and survival of patients. Many evidence suggests that chronic metabolic disorders of calcium and phosphorus in uremia patients can cause secondary hyperparathyroidism, abnormal mineral and bone metabolism, metastatic calcification, including myocardium, lung, heart valve and blood vessels. All of these factors are associated with chronic renal failure. Cardiovascular complications are the leading causes of death in hemodialysis patients. Studies have found that vascular calcification is the main cause of cardiovascular events. The mechanism of vascular calcification in hemodialysis patients is complex, with a variety of risk factors involved, with the exception of the traditional cardiovascular risk factors such as high. Age, male, smoking history, hypertension, diabetes, hyperlipidemia and so on. A large number of recent studies have found that the central link of vascular calcification is chronic inflammation and atherosclerosis, and atherosclerosis is associated with disorders of calcium and phosphorus metabolism, malnutrition, chronic inflammation and so on.
Fibroblast growth factor-23 (FGF-23), a new type of calcium phosphorus and vitamin D regulator, is significantly increased in the peripheral blood of maintenance hemodialysis patients. It is an independent risk factor for vascular calcification in hemodialysis patients. There is a widespread disorder of calcium and phosphorus metabolism and low 1,25 (OH) in maintenance hemodialysis patients. 2D3, while the treatment of oral vitamin D receptor activator (ossified three alcohol) may cause a higher level of FGF-23, then the study of whether or not it will aggravate vascular calcification is less.2009 years. The KDIGO guide recommends the use of abdominal side slice combined echocardiography to assess vascular calcification.
Objective To observe the calcification of abdominal aorta and heart valve and the thickness of carotid intima media thickness (IMT) in the maintenance hemodialysis patients at hemodialysis center, to analyze the risk factors of vascular calcification and to explore the relationship between the risk factors of FGF-23 and the risk factors of vascular calcification and the long-term oral dose of vitamin D in the treatment of vascular calcium. The role of the risk factors.
Methods 63 patients with 2013.3 to 2014.2 maintenance hemodialysis and 20 healthy controls were selected. The level of serum fibroblast growth factor -23 (FGF-23) was detected by double anti sandwich ELISA method in the two groups. The general data and clinical data of all hemodialysis patients were recorded, the related laboratory examination was perfected, and the automatic biochemical analysis was used. The apparatus detected calcium (Ca), phosphorus (Pi), alkaline phosphatase (ALP), albumin (ALB), cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), high density lipoprotein (HDL), blood glucose (Glu), creatinine (Scr), hemoglobin (Hb), and so on. Immunochemiluminescence was used to measure the parathyroid hormone (iPTH) and immunoturbidimetry. The hypersensitive C- reactive protein (hsCRP) was used to detect the calcification of the myocardium and valve, the thickness of the carotid artery intima media (IMT) and the atherosclerotic plaque in the carotid artery, and the calcification of the abdominal aorta at the lumbar side of the lumbar vertebra by the color Doppler ultrasound. The statistical treatment was statistically significant with the difference of the SPSS17.0 statistical package. The difference was statistically significant with the difference of P0.05.
Results 1, the clinical data of maintenance hemodialysis patients: the average age of 63 patients was 52.5 + 23.33 years old. The primary disease: 23 cases of chronic glomerulonephritis (36.5%), 25 cases of diabetic nephropathy (39.6%), 1 cases of polycystic kidney (1.6%), 11 cases of hypertensive nephropathy (17.5%), unexplained 3 cases (4.8%). There were 33 cases (52.38%).
2, calcification occurred in 63 cases of maintenance hemodialysis patients without vascular calcification in 33 cases (no calcification group) and 31 cases of vascular calcification (calcification group), of which 11 cases had abdominal aorta calcification, the incidence was 17.5%, 5 cases with cardiac valve calcification (aortic valve or mitral calcification, cardiac calcification), the incidence of 7.9%; neck 7.9%. Eight patients (12.7%) had intima-media thickness (IMT) greater than 0.9 mm or plaque formation, and seven patients (11.1%) had multiple calcifications.
Compared with the non calcification group, age, age, Pi, calcium and phosphorus product, ALB, hsCRP, FGF-23 had significant differences, and the difference was statistically significant. The vascular calcification rate (36.36%) in P0.05. three alcohol treatment group was significantly lower than that of non ossified three alcohol treatment group (63.33%), and the difference was statistically significant, P0.05.
3, the risk factors of vascular calcification were analyzed by multiple factor Logistic regression. The results showed that age, hsCRP, Pi, FGF-23 and not taking ossification three alcohol may be the main risk factors for vascular calcification, and high level ALB is a protective factor.
4. FGF-23 levels were positively correlated with serum phosphorus and calcium-phosphorus product, but not with ALB, ALP, Ca, hsCRP, age, dialysis age, iPTH and oral calcitriol.
5, the blood Ca (2.16 + 0.20mmol/L) in the three group of the ossification group was significantly higher than that in the non ossified three alcohol treatment group. The difference was statistically significant. The P0.05. ossification three alcohol treatment group was iPTH (33.98 + 22.39pmol/L), ALP (90.29 + 43.22U/L), hsCRP (5.40 + 3.92mg/L), and CaxPi (56.76 +) was more than the non ossified three alcohol treatment group (52.9). + 36.49pmol/L), ALP (128.20 + 82.14U/L), hsCRP (9.05 + 8.34), Ca * Pi (49.66 + 14.62mg2/ml2) obviously decreased, the difference was statistically significant, P0.05. had no significant effect on FGF-23.
Conclusion 1. The risk factors of vascular calcification in hemodialysis patients are age, serum FGF-23, Pi, hsCRP and no calcitriol. High ALB is the protective factor.
2, small dose of ossification of three alcohol may lead to a increase in blood calcium and decrease iPTH, hsCRP, ALP, Ca x Pi, which may lead to a decrease in the incidence of vascular calcification. There is no significant effect on FGF-23.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R692.5
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