Serotonergic mechanisms are involved in the hemostatic action of erythropoietin in uremic patients

Summary Recombinant human erythropoietin was administered to 12 patients with end-stage renal failure on long-term hemodialysis. They responded to the therapy with a shortening of the prolonged bleeding time, starting from the 1st week of therapy, before a significant increase in hemoglobin concentration was achieved. We also observed an increase in the activity of tissue plasminogen activator and a decrease in the activity of its inhibitor. There were no changes in platelet count but a significant increase in blood and platelet serotonin concentration was found. The shortening of the prolonged bleeding time before the correction of the anemia correlated with the rise in blood and platelet serotomin concentration during erythropoietin therapy. We suggest the possible involvement of an serotonergic mechanism in the hemostatic action of recombinant human erythropoietin.     

Effects of different treatment methods on renal anemia in maintenance hemodialysis patients with hyperparathyroidism secondary to uremia

Objective To observe the effects of three treatment methods on renal anemia in maintenance hemodialysis patients with hyperparathyroidism secondary to uremia and analyze the influencing factors of erythropoietin (EPO) dosage. Methods A total of 55 maintenance hemodialysis patients with secondary hyperparathyroidism at the hemodialysis center of Huashan Hospital affiliated to Fudan University from January 2015 to December 2016 were retrospectively divided into three groups according to different treatment methods, parathyroidectomy +forearm transplantation group (surgery group, n=16), cinacalcet treatment group (n=6), and calcitriol treatment group (n=33), respectively. The hemoglobin level and erythropoietin dosage were measured before treatment and in the 3rd month, the 6th month and the 12th month after treatment. The changes of hemoglobin and erythropoietin dosage in the three groups before and after treatment were observed, and the mixed effect model was used to analyze the difference of the change of hemoglobin and erythropoietin dosage among three groups. Multiple linear regression analysis was used to analyze the influencing factors of EPO dosage after one year. Results The levels of intact parathyroid hormone (iPTH) in the surgery group and the cinacalcet group before treatment were significantly higher than that in the calcitriol group (both P＜0.05). In the 12th month after treatment, the levels of iPTH decreased significantly in the patients of surgery group and the cinacalcet group compared with those before treatment (both P＜0.05). The levels of serum alkaline phosphatase, serum calcium and serum phosphorus in the surgery group also decreased significantly compared with those before treatment (all P＜0.05). The mixed effect model analysis showed that the hemoglobin level of surgery group was on an upward trend after the treatment, and the overall level was significantly higher than cinacalcet and calcitriol treatment group (P=0.007). There was no significant difference in the dosage change of erythropoietin (EPO) in the three groups over time. However, the intra-group comparison of the mixed effect model showed that the dosage of EPO in the 12th month was significantly lower than that of before the treatment in surgery group (P=0.007). Multiple linear regression analysis showed that dialysis vintage (B=-0.064, P=0.012) and ferritin ≥ 500 μg/L (B=0.645, P=0.032) were independent influencing factors of EPO dosage. The longer the dialysis vintage, the less EPO dosage, and more EPO dosage were observed in patients with ferritin ≥ 500 μg/L. Conclusions Parathyroidectomy and forearm transplantation is more effective in reducing EPO dosage and improving renal anemia in maintenance hemodialysis patients with secondary hyperparathyroidism. Dialysis vintage and ferritin are independent influencing factors for the dosage of EPO.     

尿毒症患者淋巴细胞亚群改变的研究

目的了解尿毒症患者淋巴细胞亚群的改变。方法采用血液细胞计数仪对血液细胞进行分类与计数;使用单激光三色流式细胞仪,分析带荧光标记单克隆抗体染色的淋巴细胞及其亚群。结果①血常规计数表明:尿毒症患者存在淋巴细胞减少症(P<0.005),中性粒细胞百分比高于正常对照组(P<0.005);②淋巴细胞亚群分析提示:尿毒症患者CD3 、CD4 、CD8 细胞百分数以及CD4/CD8比值,与正常对照组相比差异无显著性(P>0.05);NK细胞百分数明显增高(P<0.005),透析组CD8 细胞数较未透析组增加[(27.45±7.26)%Vs(20.33±7.01)%,P=0.042],单核细胞数高于正常对照组[(75.6±9.68)%Vs(63.98±12.82)%P=0.039];B淋巴细胞数低于正常对照组[(4.33±1.69)%Vs(9.49±3.30)%P=0.001];③尿毒症患者表现为Th2细胞优势(P<0.05),Th1/Th2比值显著降低(P<0.05),长期透析后上述表现无改善。结论尿毒症患者T细胞亚群表现为Th2优势,透析患者存在B淋巴细胞减少,淋巴细胞亚群的这些改变可能参与了血液透析患者免疫功能下降的发病机理。     

血液透析患者自主神经损伤及β-受体阻滞剂应用的临床研究

目的评价血液透析患者自主神经损伤及β-受体阻滞剂应用等相关因素影响.方法选择长期透析的患者及同期门诊体检人群80例.分为正常对照组、尿毒症组、常规血液透析组和β-受体阻滞剂组,分别校测患者心率变异性(HRV)时域指标并同步监测患者动态血压.进行显著性差异检验.结果①正常对照组与尿毒症组、常规血液透析组;倍他乐克组与尿毒症组、常规血液透析组间主要HRV指标存在差异显著性(P＜0.05或P＜0.01);而尿毒症组与常规血液透析组间,HRV指标两两相比差异均无显著性;②尿毒症血压正常组与尿毒症肾性高血压组之间HRV各指标比较差异有显著性(P＜0.05).结论①尿毒症患者有明显心脏自主神经系统损害;②常规血液透析不能改善尿毒症患者心脏自主神经损害,而β-受体阻滞剂治疗可明显改善尿毒症患者心脏自主神经损害,对延缓心血管并发症的发生有积极的预防作用;③尿毒症肾性高血压可加重尿毒症患者心脏自主神经系统损害,所以,除了β-受体阻滞剂的应用外,严格控制好血压亦可延缓长期透析尿毒症患者其心血管并发症的发生.     

使用不同透析膜时IL-8表达的改变

目的 了解不同透析膜对血液透析患者IL-8表达的影响。方法 采用酶联免疫吸附试验(ELISA)测定IL-8血浆水平及外周血单个核细胞(PBMC)培养上清液IL-8水平,逆转录多聚酶链反应(RT-PCR)检测基因表达。结果 聚砜膜组的IL-8血浆水平及mRNA表达低于铜仿膜组及铜氨膜组,而铜仿膜组及铜氨膜组之间无显著差异。各组透析后的IL-8血浆水平及mRNA表达均较透析前升高。铜仿膜组透析前PBMC受LPS刺激后产生的IL-8多于聚砜膜组,血透后聚砜膜组产生的IL-8较透析前升高,而铜仿膜组较透析前无明显改变。结论 再生纤维素膜(尤其是铜仿膜)导致IL-8表达改变的能力强于聚砜膜,测量IL-8表达有助于评价不同透析膜的生物相容性。     

不同透析方式对细胞因子mRNA表达和血浆水平的影响

目的 研究不同透析方式对细胞因子mRNA表达及其血浆水平的影响。方法 利用酶联免疫吸附分析(ELISA)方法和逆转录聚合酶链反应(RT-PCR)、斑点杂交方法检测了正常人(10例)、尿毒症未透析患者(10例)、腹膜透析患者(10例)及血液透析患者(14例)血浆IL-1β、TNFα、IL-6水平及外周血单个核细胞的mRNA表达。结果 正常人血浆IL-1β、TNFα、IL-6水平很低,外周血单个核细胞(PBMC)中未检测到它们的mRNA表达。尿毒症未透析患者血浆IL-1β,IL-6水平显著高于正常(P<0.05)。血液透析和腹膜透析患者PBMC细胞因子的mRNA表达均较未透析者显著升高(P<0.05),其中血透组显著高于腹膜透析组。结论 尿毒症状态可刺激细胞因子的基因表达及合成释放,透析治疗可不同程度增加细胞因子mRNA表达,腹膜透析对外周血单个核细胞的刺激作用低于血透。     

一次性使用树脂吸附柱治疗尿毒症的临床观察

目的探讨1次性使用树脂吸附柱治疗尿毒症患者的疗效与安全性。方法维持性血液透析患者31例,采用血液灌流与血液透析(HP/HD)联合治疗方法与常规血液透析(HD)方法对比(自身对照)。治疗前后检测中分子物质(MMS)、血尿素、肌酐、白蛋白、血细胞及临床症状。结果树脂吸附柱治疗血液透析患者能显著清除尿毒症患者体内的中分子物质,单次使用治疗2hMMS平均下降25.0%,最高达44.4%。而普通透析对MMS无多大影响,两者差异具有显著性(P<0.001)。同时患者的睡眠、食欲、皮肤瘙痒有不同程度的改善。未发生其他任何不良事件和副作用。结论作为MMS的清除治疗措施,1次性使用树脂吸附柱临床使用安全、疗效可靠,无毒副反应。     

尿毒症患者微炎症状况与心血管事件的相关性研究

目的 探讨维持性血液透析患者微炎症与心血管事件及存活率的关系。方法 回顾性分析广东省人民医院肾内科维持性血液透析患者178例，以超敏C反应蛋白（C-reactive protein，CRP）作为微炎症标志物，按观察开始时血清超敏CRP水平分为2组：超敏CRP正常组87例，超敏CRP升高组91例。定期监测血液透析患者的血压、超敏CRP、血红蛋白（Hb）、白蛋白（Alb）、血脂、血尿素氮（BUN）、肌酐（Scr），计算尿素清除指数（Kf／V），B超测定心脏左心房前后径（LAD）、室间隔厚度（IVST）、左心室前后径（LVD）、左心室重量指数（LVMI）及左心室射血分数（LVEF）。回顾性分析60个月，观察两组心血管事件发生率，心血管疾病致死率和总死亡率的情况。利用统计学分析两组患者CRP与心室结构功能的关系，两组生存曲线及评价微炎症与死亡危险度的关系。结果 存在微炎症的超敏C-反应蛋白升高组心室结构指标LAD、IVST、LVD、LVMI均大于正常组（P〈0．05）；而LVEF低于正常组（P〈0．05），血清超敏C反应蛋白水平与LAD、IVST、LVD、LVIM呈正相关（严0．298，r=0．331，r=0．321，r=0．342，P均〈0．05），而与LVEF呈显著负相关（r=0．343，P〈0．01）。超敏C-反应蛋白升高组心血管事件发生率及心血管事件死亡率明显高于正常组（P〈0．05）；60个月存活率升高组较正常组显著降低（P〈0．05）。生存分析显示，血清超敏CRP独立于性别、年龄、维持透析时间、血浆白蛋白、血脂、平均动脉压等因素之外，与死亡危险度显著相关（P〈0．05）。结论 尿毒症患者存在微炎症时超敏-CRP持续增高，持续增高的超敏-CRP是心血管事件发生率的独立危险因素，也是判断血液透析患者预后的重要预测因子。     

腹膜透析对尿毒症患者QT离散度的影响

目的探讨持续不卧床腹膜透析对尿毒症患者QT离散度的影响,并分析导致QT离散度延长的原因。方法:以首次进入透析并进行标准、规则腹膜透析六个月的患者为研究对象,共28例。于透析前后检测血清钾、镁、钙、磷、肌酐、尿素氮以及血HCO3-,血浆白蛋白等,做心脏彩超检查,测算出左心室重量指数;做标准十二导联心电图检查,测出QT离散度(QTd)及校正的QT离散度(QTcd),并对结果进行统计学分析。结果经过透析后,患者血清钾、磷、镁、肌酐和尿素氮水平均较透析前明显降低,具有显著意义。血钙、HCO3-较前升高,也具有显著意义。左心室重量指数较前增加,但差异无显著性,QTd较前延长,无显著意义,QTcd较前延长,有显著差异。对透析前数据进行多元相关分析显示:透析前尿毒症患者QT离散度的增加与左心室重量指数和血清肌酐水平呈显著正相关,而与血钙水平呈显著负相关。透析后患者QT离散度的增加与左心室重量指数和血清肌酐水平呈显著正相关。结论腹膜透析可能导致QT离散度延长,出现这种结果的原因与透析使左心室肥厚进一步加重有密切关系,而且本研究还发现透析后尿毒症状态改善的程度对QT离散度也有显著影响。     

尿毒症并发上消化道出血24例临床观察

对近几年收住入院的慢性肾功能衰竭（CRF）86例，对其中并发上消化道出血24例，从出血诱因、临床表现、胃镜、出血前后功能检查分析。结果发现：恶心呕吐、饮食不节、继发感染是诱发出血的主要原因一出血特点为少量、间歇出现，持续时间长而腹部症状轻微。出血后肾功能急骤恶化，与出血前相比有显著性差异（P＜0．01），是导致死亡的主要原因。