慢性肾脏病中、晚期患者矿物质和骨代谢紊乱的知晓率、治疗率和控制率

目的 调查我院慢性肾脏病（CKD）中、晚期非透析和透析患者矿物质和骨代谢紊乱的知晓率、治疗率和控制率。 方法 选取503例CKD 3期以上的非透析和透析患者,通过问卷的形式,结合实验室检查了解患者对矿物质和骨代谢紊乱的知晓率、治疗率和控制率。 结果 CKD中、晚期患者矿物质和骨代谢紊乱知识知晓率以血液透析患者最高,腹膜透析患者其次,非透析患者最低,差异有统计学意义（P < 0.01）。知识调查总得分显示,腹膜透析[11（9,12）]和血液透析[13（11,15）]患者显著高于非透析患者[6（5,8）]（P < 0.01）。相关知识的了解程度与年龄（r = -0.11,P < 0.05）呈负相关;与文化程度（r = 0.226,P < 0.01）、肾脏病病程（r = 0.597,P < 0.01）和透析龄（r = 0.366,P < 0.01）呈正相关。医护人员宣教是CKD中、晚期患者获取知识的主要渠道,在非透析、腹膜透析和血液透析患者中分别占94.0%、79.5%和69.4%。腹膜透析（88.6%）和血液透析（96.9%）患者的矿物质和骨代谢紊乱治疗率均显著高于非透析患者（58.2%）（均P < 0.01）。在控制率方面,以K/DOQI指南为标准,非透析患者血钙、血磷、钙磷乘积和甲状旁腺素（PTH）等的达标率明显优于透析患者;在各项指标的达标数量上也显著优于透析患者（均P < 0.01）。以KDIGO指南为标准,非透析（46.7%）和腹膜透析（36.9%）患者的血磷达标率均显著高于血液透析患者（23.6%）（均P < 0.01）。 结论 CKD中、晚期非透析患者矿物质和骨代谢紊乱的知晓率和治疗率较低,控制率较高;而透析患者的知晓率和治疗率较高,但控制率较低。     

血浆不对称二甲基精氨酸与慢性肾脏疾病非透析患者心血管并发症的关系

目的 探讨不对称二甲基精氨酸（ADMA）与慢性肾脏疾病（CKD）非透析患者心血管并发症（CVD）的关系。 方法 高效液相色谱-质谱联用仪检测76例患者的血浆ADMA水平，分析其与颈动脉超声、心脏超声等相关指标及既往CVD病史的关系。 结果 CKD非透析患者的血浆ADMA水平较健康对照组显著升高[(41.56±12.76) 比 (17.12±7.09) mg/L, P < 0.01]。逐步多元回归分析显示ADMA是颈总动脉内-中膜厚度（β = 0.544, P < 0.01）和左室心肌重量指数（β = 2.521, P < 0.01）的独立危险因素。既往有CVD史者其血浆ADMA水平较既往无CVD史者显著升高[(47.60±15.14)比 (36.93±8.10) mg/L，P < 0.01]。Logistic回归分析显示血浆ADMA（β = 1.117，95%CI：1.013~1.232, P < 0.05）是CKD非透析患者CVD的独立危险因素。 结论 CKD患者普遍存在CVD，ADMA可能参与了CKD非透析患者CVD的发生发展。     

慢性肾脏病患者成纤维细胞生长因子23与心脏瓣膜钙化的关系研究

目的 观察慢性肾脏病(chronic kidney disease,CKD)患者血中成纤维细胞生长因子23(fibroblast growth factor 23,FGF23)水平,探讨CKD患者FGF23的水平与心脏瓣膜钙化之间的关系.方法 选择CKD患者89例为CKD组,28例非CKD患者为对照组;将CKD组患者根据肾脏病/透析的临床实践指南(Kidney Disease Outcome Quality Initiative,K/DOQI),按估算肾小球滤过率(estimated glomerular filtration rate,eGFR)水平分为CKD 1～2期组16例,CKD 3～4期组20例,CKD 5期组16例及CKD 5D期组37例.应用酶联免疫分析法测定血清FGF23,同时测定血清全段甲状旁腺激素水平(parathyroid hormone,iPTH)、血钙、血磷、三酰甘油、血总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇等指标.所有患者应用超声心动检测心脏瓣膜是否存在钙化.比较对照组及CKD 1～2期组、CKD 3～4期组、CKD 5期组及CKD 5D期组年龄、血钙、血磷、三酰甘油、血总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、iPTH、FGF23水平及糖尿病、心血管疾病、瓣膜钙化比例.根据是否存在心脏瓣膜钙化将CKD患者89例分为瓣膜钙化组14例和无瓣膜钙化组75例,比较2组间年龄、相关指标、糖尿病、冠心病及透析所占比例.结果 ①CKD 5期组Log iPTH(2.40±0.26)及CKD 5D期组(2.47±0.20)较对照组(1.57±0.14)、CKD 1～2期组(1.54±0.10)、CKD 3～4期组(1.82±0.29)明显升高(P＜0.001),CKD 5D期组(2.67±0.54)的Log FGF23较对照组(1.37±0.11)、CKD 1～2期组(1.42±0.12)、CKD 3～4期组(1.62±0.26)、CKD 5期组(1.83±0.37)明显升高(P＜0.001).CKD 5D期组的心脏瓣膜钙化比例(12/37)明显高于对照组(2/28)、CKD 1～2期组(2/26)、CKD 3～4期组(1/20)及CKD 5期组(0/16),差异有统计学意义(P＜0.05);②瓣膜钙化组的年龄[(73.3±9.9)岁]、三酰甘油[(4.10±2.09) mmol/L]、Log FGF23 (2.52±0.71)、透析患者所占比例(11/14)较无钙化组的年龄[(64.8±12.6)岁]、三酰甘油[(1.90±1.59)mmol/L]、Log FGF23(1.96±0.62)、透析患者所占比例(26/75)明显升高,差异有统计学意义(P＜0.05);③Logistic回归分析显示,年龄、Log FGF23、血总胆固醇及糖尿病病史是影响心脏瓣膜钙化的独立影响因素.结论 CKD患者血清FGF23升高,且随着肾功能的恶化,FGF23水平呈升高趋势,FGF23升高为心脏瓣膜钙化的危险因素.     

慢性肾脏病患者成纤维细胞生长因子23与肾功能及钙磷代谢的关系

目的 探讨慢性肾脏病（CKD）患者随着肾功能的变化,其成纤维细胞生长因子23（FGF23）与钙磷代谢的关系。 方法 研究对象为2008年8月至2009年4月在上海交通大学附属第一人民医院肾内科住院的初诊CKD患者72例,按照肾小球滤过率（GFR）水平分为5组,另设健康对照组20例。抽取受试者静脉血并分离血清,以酶联免疫法检测FGF23、25（OH）VitD3、1,25（OH）2VitD3;全自动生化分析仪测量钙（Ca）、磷（P）、血肌酐（Scr）、尿素氮（BUN）、白蛋白（Alb）水平;免疫放射法测定全段甲状旁腺激素（iPTH）。 结果 CKD患者血清FGF23水平随GFR降低逐渐升高,在CKD4期和5期时,血FGF23、P、iPTH上升明显,1,25（OH）2VitD3显著下降,与CKD1期差异有统计学意义（均P < 0.05）。CKD2~3期与CKD1期的FGF23、P、Ca、iPTH、活性维生素D水平差异均无统计学意义。血Ca、25（OH）VitD3随着肾功能下降有降低趋势,但各期间差异均无统计学意义。Pearson相关分析显示,CKD1~5期logFGF23与P、logiPTH呈正相关（r = 0.653,P < 0.01;r = 0.800,P < 0.01）,与GFR、1,25（OH）2VitD3呈负相关（r = -0.753,P < 0.01;r = -0.265,P < 0.05),与Ca、25（OH）VitD3无相关。CKD1~3期logFGF23与logiPTH呈正相关(r = 0.374,P < 0.05),而与Ca、P、25（OH）VitD3、1,25（OH）2VitD3、GFR均无相关。CKD4~5期log FGF23与P、logiPTH呈正相关（r = 0.381,P < 0.05;r = 0.515,P < 0.01）,与GFR呈负相关（r = -0.654,P < 0.01）,与Ca、25（OH）VitD3、1,25（OH）2VitD3无相关。 结论 随着肾功能减退,血清FGF23、P、iPTH水平逐渐升高,活性维生素D水平逐渐下降,尤以CKD4~5期明显。在肾脏病早期阶段（CKD1~3期）血iPTH水平与FGF23有关。当GFR<30 ml/min时,肾功能状态、血磷、血iPTH均可影响血FGF23水平。     

慢性肾衰竭患者血清骨保护素浓度与心脏瓣膜钙化的关系

目的探讨慢性肾衰竭（CRF）患者血清骨保护素（OPG）水平与心脏瓣膜钙化的关系。方法以75例CRF患者[非透析组（ND）25例,腹透组（PD）28例,血透组（HD）22例1和10例健康人（对照组）为研究对象,采用酶联免疫复合物法测定患者血清OPG水平,分析其与心脏瓣膜钙化之间的关系。结果各组CRF患者血清中OPG水平[ND组（4.77±1.74）μg/L、PD组（5.22±1.57）μg/L、HD组（5.35±1.72）μg/L]显著高于对照组[（2.04±0.57）μg/L,P〈0.01]。OPG水平与年龄（r=0.311,P〈0.05）和C反应蛋白水平（r=0.353,P〈0.01）呈正相关。根据有无心脏瓣膜钙化分组后发现,存在瓣膜钙化的CRF患者OPG水平较无瓣膜钙化组显著升高[（6.28±1.66）μg/L比（4.59±1.40）μg/L,P〈0.01]。Logistic回归分析显示血清OPG水平是CRF患者心脏瓣膜钙化发生的一项独立危险因素（P〈0.01）。结论在CRF患者中,血清OPG水平与心脏瓣膜钙化相关。     

慢性肾脏病患者血栓调节蛋白与动脉粥样硬化的相关性

目的 探讨慢性肾脏病(CKD)患者血栓调节蛋白（Tm）水平与动脉粥样硬化（AS）的相关性。 方法 以北京朝阳医院肾内科住院的96例CKD患者为对象,其中血液透析32例,非透析64例;30例健康志愿者为对照。参试者均于清晨空腹采静脉血,分别测定Scr、胆固醇、三酰甘油、高密度脂蛋白、低密度脂蛋白、C反应蛋白、血红蛋白及血栓调节蛋白。应用彩色多普勒超声检测颈动脉内膜中层厚度（IMT）。对血栓调节蛋白与IMT及相关参数进行相关分析。 结果 CKD患者血栓调节蛋白为（12.15±3.04） mg/L,显著高于健康对照组的（3.12±0.23） mg/L（P < 0.01）。血液透析组血栓调节蛋白为（16.89±3.35） mg/L,显著高于非透析组的（9.78±2.49） mg/L（P < 0.01）。血液透析组IMT值为（1.13±0.31） mm,斑块检出率为48.5%,均显著高于非透析治疗组的（0.95±0.33） mm和28.7%（均P < 0.05）。96例CRF患者的Tm水平与IMT呈正相关（r = 0.335,P < 0．01）。动脉病变程度越重者,血浆Tm水平越高。多元逐步回归分析结果显示,Tm（OR=1.13,95%CI 1.010~1.121）、SBP（OR=1.09,95%CI 1.009~1.114）、CRP（OR=1.22,95%CI 1.216~2.007）分别与CKD患者IMT独立相关。 结论 CKD患者Tm水平与IMT独立相关。血管内皮细胞损伤与CKD患者动脉粥样硬化并发症密切相关。Tm有可能成为血管内皮细胞损伤或功能紊乱的标志物。     

中晚期CKD患者腹主动脉钙化发生情况及危险因素分析

目的：分析中晚期CKD患者腹主动脉钙化的发生情况和危险因素。方法：63例透析及非透析CKD患者进行腹部侧位片的检查,分析腹主动脉钙化发生情况及影响因素。结果：中晚期CKD患者腹主动脉钙化发生率为54%;腹主动脉钙化与年龄、血磷水平、钙磷乘积和低密度脂蛋白水平呈正相关（P〈0.05）。结论：中晚期CKD患者腹主动脉钙化高发,远端起病,年龄、血脂、钙磷水平影响其程度。     

维持性血液透析患者主动脉瓣和二尖瓣钙化的危险因素

目的 探讨主动脉瓣和二尖瓣钙化发病的相关危险因素。 方法 对符合标准的维持性血液透析（MHD）患者（年龄≥18岁,透析龄>6个月,排除曾因瓣膜疾病行外科手术或介入治疗者）,采用超声心动图检查心脏瓣膜钙化情况。采用Logisitc回归分析主动脉瓣和二尖瓣钙化的危险因素。 结果 在入选的181例（男98例,女83例）MHD患者中,94例（51.9%）主动脉瓣或二尖瓣钙化,其中主动脉瓣钙化90例（49.7%）,二尖瓣钙化30例（16.6%）,主动脉瓣和二尖瓣双瓣膜钙化26例（14.4%）。多因素Logistic回归分析表明年龄（β = 5.52, P = 0.007）、透析龄（β = 6.99,P = 0.039）和前白蛋白（β = -12.616,P = 0.004）与主动脉瓣钙化独立相关;年龄（β = 0.085,P = 0.05）与二尖瓣钙化呈弱正相关;透析龄（β = 6.057,P = 0.002）、原发性高血压病病史（β = 3.054,P = 0.008）、血红蛋白（β = -0.061,P = 0.035）和β2微球蛋白（β = 7.63,P = 0.01）与二尖瓣钙化独立相关。 结论 MHD患者主动脉瓣及二尖瓣钙化多发,且以主动脉瓣钙化更多见。年龄、透析龄和低前白蛋白血症是主动脉瓣钙化的危险因素,而二尖瓣钙化的危险因素包括年龄、透析龄、原发性高血压病病史、贫血和高β2微球蛋白血症。     

结直肠癌患者手术前后循环DNA 水平的变化及其意义

目的：探讨结直肠癌患者手术前后循环DNA水平的变化及其临床意义。方法：检测42例结直肠癌患者术前、术后3,14,30 d循环DNA水平,并检测同期14例健康体检者循环DNA水平作为对照。结果：结直肠癌患者术前循环DNA水平明显高于健康人[（92.25±46.88）ng/mL vs.（22.14± 16.16）ng/mL]（P<0.01）;结直肠癌术前循环DNA水平在不同年龄、性别、肿瘤部位分组间差异无统计学意义（P=0.293,P=0.244,P=0.135）。结直肠癌患者术后3 d循环DNA水平达（114.95±62.41）ng/mL,较术前明显升高（P<0.01）,但在术后14,30 d分别为（38.50± 37.71）ng/mL与（31.69±41.48）ng/mL,明显低于术前（均P<0.01）。结论：循环DNA水平在结直肠癌患者中升高,且术后早期一过性进一步升高,随后明显下降。循环DNA水平有望成为结直肠癌术后监测肿瘤状态和评价疗效的标志物。

     

血液透析患者颈总动脉僵硬度与胰岛素抵抗的关系

目的 探讨维持性血液透析患者颈总动脉僵硬度与胰岛素抵抗的关系。 方法 选取80例非糖尿病、病情稳定的血液透析患者为研究对象。采用超声血管壁跟踪系统（Echo-tracking）在血液透析结束后1 h测定颈总动脉硬化参数β作为评价大动脉僵硬度的指标。胰岛素抵抗用内环境稳定模型评估胰岛素抵抗法（HOMA-IR）进行评价。常规检测血红蛋白、白蛋白、总胆固醇、高密度脂蛋白、低密度脂蛋白、三酰甘油、脂蛋白(a)、载脂蛋白A1、载脂蛋白B、C反应蛋白、钙、磷、肌酐。用独立样本t检验、Pearson及多元逐步回归法分析各参数关系。 结果 既往有心血管病史者颈总动脉硬化参数β大于无心血管病史者（11.41±4.13比9.75±3.63，P < 0.05）。Pearson相关分析显示，颈总动脉硬化参数β与HOMA-IR（r = 0.321，P < 0.01、年龄（r = 0.376，P < 0.01）、脉压（r = 0.267，P < 0.05）、透析龄（r = 0.219，P < 0.05）呈正相关。多元逐步回归结果显示，HOMA-IR（β = 0.228，P < 0.05）、年龄（β = 0.308，P < 0.01）是颈总动脉硬化参数β增加的独立危险因素。 结论 在血液透析患者，胰岛素抵抗可能通过参与大动脉僵硬的发生，导致心血管疾病发病率和病死率增加。     

Serum levels of soluble secreted α-Klotho are decreased in the early stages of chronic kidney disease, making it a probable novel biomarker for early diagnosis

Background

α-Klotho was first identified as an aging gene and was later shown to be a regulator of phosphate metabolism. Fibroblast growth factor 23 (FGF23) is the key regulator of phosphate metabolism. Serum levels of soluble α-Klotho in chronic kidney disease (CKD) patients have not previously been determined, especially in relation with FGF23 and creatinine levels. This study was designed to investigate whether serum soluble α-Klotho levels are modulated by renal function, age, and FGF23 level in CKD patients. This study is the first report on the utility of measuring soluble α-Klotho levels in human CKD.

Methods

A total of 292 CKD patients were enrolled. Serum samples were collected, and FGF23 and soluble α-Klotho levels were measured using enzyme-linked immunosorbent assay kits. In addition, serum creatinine, hemoglobin, albumin, calcium, and phosphate levels were measured.

Results

Serum soluble α-Klotho levels were associated positively with estimated glomerular filtration rate (eGFR) (P?P?P?=?0.0001). Serum FGF23 levels were associated positively with serum creatinine and negatively with eGFR. FGF23 levels were significantly increased in stage 5 compared with stage 1 CKD. Soluble α-Klotho was associated inversely with log-transformed FGF23 level (P?Conclusion Our data indicate that soluble α-Klotho levels are significantly decreased in stage 2 CKD compared to stage 1, and not only in the advanced stages of the disease. Soluble α-Klotho may thus represent a new biomarker for the diagnosis of CKD, especially in the early stage.     

Expression of core?binding factor alpha 1 and collagen Ⅱ in patients with chronic kidney disease stage 5

Objective To study the relationship between the medial artery calcification and expression of core?binding factor alpha 1 (Cbfα?1) and collagen Ⅱ (ColⅡ) in chronic kidney disease(CKD) stage 5 patients. Methods Pieces of radial arteries were taken from 40 patients with CKD stage 5 during internal arteriovenous fistula operation. Ten patients with subtotal gastrectomy and normal renal function were chosen as control. The vessels were examined for calcification by von Kossa stain and for the presence of Cbfα?1 and ColⅡ by immunohistochemistry. According to von Kossa stain, CKD stage 5 patients were divided into no calcification group, mild?moderate calcification group and severe calcification group. Other related factors including serum calcium，phosphate, intact parathyroid hormone (iPTH), C?reactive protein (CRP), triglyceride(TG), cholesterol(TC) and low?density lipoproteins(LDL) were also detected. Results Seventeen (42.5%) of CKD Stage 5 patients showed vascular calcification, while calcification was not found in controls. Most calcification occurred in medial layer．Positive immunohistochemical staining of core?binding factor and ColⅡ was found in the smooth muscular cell plasma of medial layer in the vessels with calcification. However, above positive staining was also observed in 78.3% of no calcification group. But there was little staining in control group. Positive staining score of Cbfα?1 and ColⅡ in severe calcification group was significantly higher than that in no calcification group. Same findings were obtained in mild?moderate calcification group, but the difference between them was not statistically significant. CRP and Ca×P were positively correlated with staining score of Cbfα?1 and ColⅡ. Serum phosphate was positively correlated with Cbfα?1 (r=0.786, P<0.01) and ColⅡ (r=0.785, P<0.01) respectively． Conclusions 42.5% of CKD stage 5 patients in our group shows vascular calcification, which occurrs mainly in medial layer. High expression of Cbfα?1 and ColⅡ can be observed in vascular calcification of radial arteries, which is earlier than vascular histological changes. Cbfα?1 and ColⅡ may be involved in the development of vascular calcification.     

终末期肾病患者心血管事件与血清胎球蛋白A及冠脉钙化的关系

目的探讨终末期肾病（ESRD）患者心血管事件发生与血清胎球蛋白A及冠脉钙化的关系。方法对38例ESRD初始血液透析患者进行血清胎球蛋白A及相关因素检测，对其中的29例患者进行冠状动脉多层螺旋CT钙化评价研究。所有38例患者随访时间为18个月。22例非ESRD慢性肾脏病（CKDⅡ～Ⅲ期）患者人选对照组。结果38例ESRD初始透析患者在18个月随访期内出现心血管事件30例次，因心血管事件死亡者6例，占15．79％，而非ESRD患者心血管事件仅3例次（P〈0．01）且无一例死亡（P〈0．05）。ESRD血清低胎球蛋白A组心血管事件显著高于ESRD血清高胎球蛋白A组（P〈0．01）。多元逐步回归分析显示，心血管事件与血清胎球蛋白A（P〈0．01）、C反应蛋白（CRP）（P=0．0014）及低密度脂蛋白C（LDL-C）（P=0．008）密切相关。18／29例（62．07％）有冠状动脉钙化。冠状动脉钙化患者心血管事件比无冠状动脉钙化患者显著增多（P〈0．01）。冠脉钙化的ESRD患者血清胎球蛋白A水平较无冠脉钙化的ESRD患者明显下降（P〈0．01）。冠脉钙化与胎球蛋白A下降及高血磷有关（P〈0．01，P〈0．01）。结论ESRD透析患者心血管事件和（或）心血管事件死亡可能与血清胎球蛋白A下降及冠状动脉钙化有关。     

Relationship of Fibroblast Growth Factor 23 with Left Ventricle Mass Index and Coronary Calcificaton in Chronic Renal Disease

Background : to evaluate the relationship between FGF23 and changes in biochemical parameters, left ventricle mass index, coronary, aortic and, valve calcifications. Methods : Totally 185 patients with chronic renal disease were included in this prospective, cross-sectional study. The patients were stratified according to GFR levels (mL/min/1.73m(2)) into 5 groups: ≥60, 45-59, 30-44, 15-29 and <15 (group 1-5 respectively).Biochemical parameters, serum FGF23 levels were measured. Echocardiographic assessments and Coronary artery calcification (CAC) with multidetector computerized tomography (MDCT) were done, left ventricle muscle mass (LVMI) was measured all patients. Results : Left ventricular hypertrophy (LVH), aortic and valve calcification were detected in 27.8%, 25.3% and 12% of patients respectively. CAC was detected in 18 patients. LVMI and FGF23 levels were found to increase proportionally with the severity of renal failure. A significant positive correlation between FGF-23 level and serum phosphate, log(PTH), and CaxP product was found. While a correlation between FGF-23 and valve calcification was detected, no correlation could be detected with LVMI, LVH, coronary and aortic calcification. Conclusion: In CKD, circulating FGF-23 and LVMI levels gradually increase with declining renal function such that by the time patients reach end-stage renal disease. Correlation between log(FGF23 )and valve calcification was significant, whereas no statistically significant relationship was found between log(FGF23 )and LVMI, LVH, aortic and coronary artery calcifications.     

尿毒症患者桡动脉钙化与骨密度及血清骨代谢指标的关系

目的 观察尿毒症患者桡动脉钙化情况并分析其与骨密度及血清骨代谢指标改变的关系.方法 以67例尿毒症患者为对象,取内瘘手术切除的桡动脉段,von Kossa染色及透射电镜检测血管钙化情况;检测Scr、血钙、磷、甲状旁腺素(iPTH);测定腰椎、股骨颈骨密度(BMD);放射免疫法测定血清25羟维生素D3 (25OHD)、1,25羟维生素D3[1,25(OH) 2D];ELISA法测定成纤维生长因子(FGF) 23、骨特异性碱性磷酸酶(BAP)、骨钙素(BGP)与Ⅰ型胶原吡啶交联物(ICTP).以23例健康体检者为对照,仅接受血清及骨密度检查.结果 von Kossa染色见24例(35.8％)尿毒症患者桡动脉中膜明显钙沉积;电镜发现中膜平滑肌细胞由 收缩型向分泌型转化,胞内有较多含钙囊泡,基质胶原明显增加伴钙磷结晶附着,程度与钙化评分一致.与对照组比较,尿毒症患者血磷、iPTH、FGF23、BGP、ICTP显著增加(均P＜0.05),血钙、25OHD、1,25(OH)2D显著降低(均P＜0.01),腰椎、股骨颈BMD也显著降低(均P＜0.01).相关分析显示,桡动脉钙化与糖尿病、股骨颈及腰椎骨密度Z值、ICTP、FGF23相关(r=0.62、-0.43、-0.25、0.34、0.86,P=0.000、0.012、0.001、0.018、0.000),与iPTH无相关(r=-0.08,P=0.306).按iPTH水平分层后,低iPTH(＜150 ng/L)组、高iPTH(＞300 ng/L)组患者iPTH与钙化相关(r=-0.41、0.31,P=0.044、0.023).多元回归分析显示,股骨颈骨密度Z值、ICTP、FGF23是桡动脉钙化的独立危险因素(β=-0.221、0.181、0.260,P=0.021、0.024、0.036).结论 尿毒症桡动脉钙化与平滑肌细胞合成和分泌较多的含钙基质有关,骨密度降低、骨转化率异常、骨吸收增加、血清FGF23水平增加是其危险因素.     

Mineral and bone disorder in patients with chronic kidney disease: a cross - sectional single center study

Objective To investigate and analyze the mineral and bone disorder (MBD) in the patients with chronic kidney disease (CKD), reveal the change of related indexes of CKD-MBD. Methods A cross-sectional study was carried out in the First Affiliated Hospital of Harbin Medical University. From October 2011 to May 2014, 1318 inpatients and hemodialysis outpatients were enrolled. Parameters related to MBD, including serum phosphorus (P), total calcium (t - Ca), intact parathyroid hormone (iPTH) and alkaline phosphatase (AKP) were analyzed. Last, it was analyzed with multiple regression analysis to related factors of the secondary hyperparathyroidism (SHPT) in patients with CKD. Results Serum calcium, phosphorus and iPTH had no obvious abnormalities at the early stages of CKD [GFR＞60 ml•min-1•(1.73 m2）-1], and relatively stable before GFR＞30 ml•min-1•(1.73 m2)-1. After entering the CKD4 stage, serum phosphorus, iPTH increased sharply and serum calcium decreased obviously along with the decreased glomerular filtration rate (GFR). Serum P, t-Ca and iPTH levels were statistically significant in CKD 1 to 5D patients, respectively, serum P: (1.13±0.20) mmol/L, (1.14±0.22) mmol/L, (1.26±0.23) mmol/L, (1.48±0.34) mmol/L, (2.05±0.61) mmol/L and (2.08±0.58) mmol/L; serum t-Ca (mmol/L) (2.35±0.13) mmol/L, (2.35±0.12) mmol/L, (2.35±0.15) mmol/L, (2.26± 0.18) mmol/L, (2.07±0.29) mmol/L and (2.31±0.26) mmol/L; iPTH: 57.8(45.6, 91.8) ng/L, 54.1(37.8, 74.6) ng/L, 71.6(45.8, 102.2) ng/L, 131.1(81.7, 205.1) ng/L, 277.5(173.6, 395.3) ng/L and 354.9 (194.4, 720.3) ng/L; The stepwise logistic regression analysis showed: hypocalcemia (OR=3.32, P＜0.01) and decreased GFR (OR=5.28, P＜0.01) were independent risk factors of iPTH elevation at stage CKD3～5. Conclusions From the beginning of the CKD3 stage, serum t - Ca, P, iPTH level began to be relatively abnormal as renal function declined. Hyperphosphatemia, SHPT has not been improved significantly in CKD5D stage patients even with hemodialysis. The regulation of hemodialysis on serum calcium showed "overcorrecting" phenomenon.     

血液透析患者血清FGF23水平的影响因素及其与矿物质骨代谢异常的关系研究

目的分析维持性血液透析患者血清成纤维细胞生长因子23(FGF23)水平的影响因素,并探究其与矿物质骨代谢异常及血管钙化的关系。 方法2018年1月至2月期间纳入在南方医科大学附属东莞市人民医院进行维持性血液透析3个月以上患者380例,记录其性别、年龄、透析龄、透析充分性及降磷药物使用情况。透析前抽取血清检查钙、磷、全段甲状旁腺素(iPTH)及碱性磷酸酶等矿物质骨代谢指标,以及血红蛋白、白蛋白、血糖、血脂、血清超敏C反应蛋白(hs-CRP)、血清β2微球蛋白等指标。使用酶联免疫吸附法(ELISA)检测血清FGF23,多层螺旋CT进行冠状动脉钙化评分(MSCT)。采用t检验和卡方检验对维持性血液透析患者FGF23的影响因素进行单因素分析,之后使用多元线性逐步回归方法进行多因素分析。 结果本中心维持性血液透析患者血清FGF23中位数水平为8 905.3 ng/L,根据患者的FGF23水平50%中位数将患者分为低水平组(组1)和高水平组(组2)两组。单因素分析结果表明,透析龄、每次透析时间、透析超滤量及使用非含钙降磷药物和透析频次为FGF23水平的影响因素。透析龄更大,每次透析时间长,每周透析次数多、透析超滤量大的患者FGF23水平更高(均P<0.05)。在FGF23水平高于中位数的患者中,尿素氮、血肌酐和血清β2微球蛋白水平更高(均P<0.05)。多元线性回归分析显示,透析龄长和血肌酐升高是FGF23升高的危险因素(均P<0.001)。同时,高FGF23水平与血清钙、血清磷、iPTH水平和高冠状动脉钙化评分相关。 结论透析龄、每次透析时间、透析超滤量、透析频次、尿素氮、血肌酐、血清β2微球蛋白水平与维持血液透析患者FGF23升高有关。透析龄长和血肌酐高是FGF23升高的危险因素。FGF23与维持性血液透析患者矿物质骨代谢和冠状动脉钙化明显相关。     

Association of serum FGF23 with abdominal aortic calcification and outcomes in maintenance hemodialysis patients

Objective To explore the association of fibroblast growth factor-23 (FGF23) with abdominal aortic calcification(AAC) and adverse outcomes in maintenance hemodialysis patients. Methods One hundred and fourteen cases of MHD patients were collected prospectively. Serum intact FGF23 was detected by ELISA. Abdomen lateral plain was used as a criteria to determine the abdominal aortic calcification and the abdominal aortic calcification score was counted. Logistic regression analysis was used to determine the risk factors of AAC. Kaplan-Meier analysis was applied to compare the survival rate among different groups and COX regression analysis was used to determine the association of FGF23 and mortality in MHD patients. Results Seventy-six patients present abdominal aortic calcification. The median of AACS was 4.0(0.0, 11.0). The median level of FGF23 was 7277.4(2535.0, 9990.8) pg/ml. The median follow-up duration was 72.0(67.8, 72.8) months. During the follow-up, 22 patients (19.3%) died of all-cause death and 17 cases (14.9%) died of cardiovascular diseases. Serum FGF23 level was positively correlated with AAC (r=0.285, P=0.002). Logistic regression analysis showed that longer age (OR=1.059, 95%CI: 1.020-1.100, P=0.003) and dialysis vintage (OR=1.009, 95%CI 1.000-1.017, P=0.039), smoking history (OR=3.010, 95%CI 1.177-7.696, P=0.021) and higher FGF23 level(OR=2.831, 95%CI 1.010-7.937, P=0.048) were independent risk factors of moderate to severe AAC in MHD patients. Kaplan-Meier survival curves showed that the patients with AACS≥5 had significantly higher all-cause mortality(P=0.028) and CVD mortality (P=0.035) than those with AACS＜5. However, the Kaplan-Meier analysis showed no significant difference regarding the level of serum FGF23 with the all-cause and CVD mortality. Cox regression demonstrated that FGF23 was not associated with increased mortality risk, neither in crude nor in multivariate adjusted models. Conclusions Abdominal aortic calcification had a high prevalence in MHD patients. The all-cause and CVD mortality was higher in patients with moderate to severe AAC. FGF23 was an independent risk factor of moderate to severe AAC, but it can't yet be a predictor for the all-cause and CVD mortality of MHD patients.     

Effects of Phosphate Binders in Moderate CKD

Some propose using phosphate binders in the CKD population given the association between higher levels of phosphorus and mortality, but their safety and efficacy in this population are not well understood. Here, we aimed to determine the effects of phosphate binders on parameters of mineral metabolism and vascular calcification among patients with moderate to advanced CKD. We randomly assigned 148 patients with estimated GFR=20-45 ml/min per 1.73 m(2) to calcium acetate, lanthanum carbonate, sevelamer carbonate, or placebo. The primary endpoint was change in mean serum phosphorus from baseline to the average of months 3, 6, and 9. Serum phosphorus decreased from a baseline mean of 4.2 mg/dl in both active and placebo arms to 3.9 mg/dl with active therapy and 4.1 mg/dl with placebo (P=0.03). Phosphate binders, but not placebo, decreased mean 24-hour urine phosphorus by 22%. Median serum intact parathyroid hormone remained stable with active therapy and increased with placebo (P=0.002). Active therapy did not significantly affect plasma C-terminal fibroblast growth factor 23 levels. Active therapy did, however, significantly increase calcification of the coronary arteries and abdominal aorta (coronary: median increases of 18.1% versus 0.6%, P=0.05; abdominal aorta: median increases of 15.4% versus 3.4%, P=0.03). In conclusion, phosphate binders significantly lower serum and urinary phosphorus and attenuate progression of secondary hyperparathyroidism among patients with CKD who have normal or near-normal levels of serum phosphorus; however, they also promote the progression of vascular calcification. The safety and efficacy of phosphate binders in CKD remain uncertain.