血清胱抑素C在高血压早期肾损害诊断中的应用价值

目的 探讨血清胱抑素C （CysC）在高血压早期肾损伤中的诊断价值。方法 选择2016年6月~12月池州市第二人民医院收治的122例高血压患者为研究对象,使用生化分析仪检测CysC、血清肌酐（SCr）、尿素（Urea）,依据CKD-EPI_SCr方程计算出估计肾小球滤过率（eGFR）,将上述患者分为eGFR正常组[G1组,eGFR ≥ 90 mL/（min·1.73 m²）]25例；轻度损害组[G2组,eGFR 60~89 mL/（min·1.73 m²）]71例；中度及以上损害组[G3组,eGFR<60 mL/（min·1.73 m²）]26例。采用Pearson相关分析CysC与eGFR的相关性,并比较各组间以及组内CysC与SCr、Urea的阳性率,logistic回归筛选有意义变量,比较CysC在G2、G3组的受试者工作曲线（ROC）下面积（AUC）。结果 CysC在G2组的阳性率为42.25%,而SCr和Urea均未检出异常,组内3个指标差异有统计学意义（P<0.05）；G3组CysC与SCr、Urea阳性率分别为88.46%、50.00%、39.28%,差异有统计学意义（P<0.05）；CysC在3组中阳性率的差异有统计学意义（P<0.05）,Pearson相关分析显示,CysC与eGFR呈负相关（r=-0.824,P<0.05）,G2和G3组logistic回归入选变量均为CysC,AUC分别为0.691、0.922。结论 CysC是高血压早期肾损伤的灵敏诊断指标之一,敏感性优于SCr、Urea。     

血清同型半胱氨酸与头颈部动脉粥样硬化的关系研究

目的 探讨血清同型半胱氨酸（HCY）与头颈部动脉粥样硬化关系。方法 选择2016年1月至2016年12月合肥市第二人民医院行头颈部CT血管造影术（CTA）明确有动脉粥样硬化病变患者119例，根据头颈部动脉CTA结果，将轻度及轻度以上狭窄的106例患者纳为试验组，将无动脉狭窄的13例患者纳为对照组，比较两组患者的血清HCY水平。再根据头颈部动脉狭窄程度，分为轻度狭窄组（28例）、中度狭窄组（29例）与重度狭窄组（49例），比较3组患者血清HCY水平。结果 试验组患者血清HCY水平为（17.76±15.14）μmol/L，对照组为（10.95±2.73）μmol/L，两组差异有统计学意义（P<0.05）。轻度狭窄组血清HCY水平（12.77±8.05）μmmol/L，中度狭窄组为（16.01±8.39）μmmol/L，重度狭窄组为（22.20±20.29）μmmol/L，重度狭窄组与中度狭窄组、轻度狭窄组的血清HCY水平比较，差异有统计学意义（P<0.05）。结论 HCY在头颈动脉粥样硬化中起着一定作用，HCY对头颈部动脉粥样硬化的作用机制及长期影响有待深入研究。     

大气细颗粒物浓度与儿童咳嗽变异性哮喘的相关性

目的 探讨大气细颗粒物（PM2.5）浓度与儿童咳嗽变异性哮喘的关系。方法 选择2015年4月至2016年4月南京医科大学附属淮安第一人民医院诊断为咳嗽变异性哮喘儿童48例（咳嗽变异性哮喘组）和典型哮喘儿童50例（典型哮喘组）,同期选择慢性肺炎儿童50例（肺炎组）和健康儿童50例（对照组）,比较发病1个月内环境中平均PM2.5浓度,检测血清淋巴细胞比率、CD⁺₄/CD⁺₈、IgE、肺通气指标水平。结果 ①咳嗽变异性哮喘组和典型哮喘组的平均PM2.5浓度高于肺炎组和对照组[（85.6±10.3）、（76.4±11.4）μg/m³ vs（41.3±12.5）、（25.9±10.5）μg/m³],差异有统计学意义（P<0.05）;②咳嗽变异性哮喘组和典型哮喘组的淋巴细胞比率和IgE水平高于其他两组,CD₄⁺/CD₈⁺低于其他两组,差异均有统计学意义（P<0.05）;③咳嗽变异性哮喘组的FEV₁% Pred、FEV₁/FVC和MMEF% Pred分别为（88.7±13.5）%、（80.2±7.8）%、（78.6±15.4）%,典型哮喘组分别为（85.4±14.6）%、（76.3±7.6）%、（72.5±16.3）%,均分别低于其他两组（P<0.05）,而咳嗽变异性哮喘组相关数据与典型哮喘组则基本一致（P>0.05）。结论 PM2.5与儿童咳嗽变异性哮喘发作有关,免疫调节和通气功能降低与典型哮喘改变可能一致。     

旋转皮瓣和改良菱形皮瓣修复面部缺损的效果比较

目的 探讨旋转皮瓣和改良菱形皮瓣在修复面部缺损方面的效果差异。方法 选取2012年12月至2015年7月在西安市第九医院接受治疗的面部缺损中度以上的患者共83例,并随机分为两组,即旋转皮瓣组35例,改良菱形皮瓣组48例,对比两组术前皮损面积、术后切口长度以及术后满意程度。结果 旋转皮瓣组患者术前皮肤缺损面积为（2.41±1.86）cm²,改良菱形皮瓣组为（2.49±1.93）cm²,差异无统计学意义（t=0.189,P=0.850）。旋转皮瓣组患者术后切口长度（5.29±0.82）cm,高于改良菱形皮瓣组的（2.62±0.76）cm,差异有统计学意义（t=8.985,P<0.001）。旋转皮瓣组额部满意度评分为（8.40±1.30）分,改良菱形皮瓣组为（8.50±1.10）分,差异无统计学意义（t=0.161,P=0.874）;旋转皮瓣组鼻部满意度评分为（7.20±1.00）,改良菱形皮瓣组为（7.10±1.20）,差异无统计学意义（t=0.208,P=0.837）;旋转皮瓣组面侧颧颊部满意度评分为（8.5±1.00）,高于改良菱形皮瓣组的（7.2±1.20）,差异有统计学意义（t=3.292,P=0.003）。结论 中等大小的皮肤缺损,旋转皮瓣和改良菱形皮瓣均拥有良好的治疗效果,但旋转皮瓣对颧颊部皮肤缺损的修复效果优于改良菱形皮瓣。     

艾塞那肽对糖尿病自主神经病变患者氧化应激状态、血糖水平及心率变异性的影响

目的 探讨艾塞那肽对糖尿病自主神经病变（DAN）患者氧化应激、血糖及心率变异性的影响。方法 选取2015年4月—2017年4月在北京航天总医院治疗的DAN患者128例,根据患者最终选取的治疗方案分为观察组（n=67）和对照组（n=61）,对照组给予常规糖尿病治疗方案,观察组在对照组基础上给予sc艾塞那肽,2次/d,5 μg/次,总疗程12周。观察两组患者氧化应激、血糖及心率变异性情况。结果 观察组治疗后餐后2 h血糖（2h-PG）、糖化血红蛋白（HbA1c）和体质量指数（BMI）分别为（7.02±1.37）mmol/L、（6.71±1.82）%和（24.89±1.03）kg/m²,均显著低于对照组（P<0.05）。观察组治疗后丙二醛（MDA）、同型半胱氨酸（Hcy）分别为（2.51±0.91）mol/L和（12.03±3.11）μmmol/L,均显著低于对照组（P<0.05）,而超氧化物歧化酶（SOD）为（37.10±5.03）mU/L,显著高于对照组（P<0.05）。观察组治疗后总体标准差（SDNN）、差值均方的平方根（RMSSD）、爱丁堡指数（PNN50）、极频（VLF）、低频（LF）、高频（HF）分别为（50.25±8.10）ms、（26.02±5.55）ms、（12.01±1.32）%、（86.02±8.22）ms²、（71.14±7.05）ms²、（42.10±8.33）ms²,均显著高于对照组（P<0.05）,而LF/HF为（1.72±0.48）,显著低于对照组（P<0.05）。结论 艾塞那肽能有效控制DAN患者血糖,改善患者BMI和心率变异指标,减轻氧化应激反应。     

外周血中性粒细胞与淋巴细胞比值对慢性鼻窦炎患者诊断及术后复发判断的价值

目的 探讨外周血中性粒细胞数与淋巴细胞数比值（NLR）对慢性鼻窦炎（CRS）患者的诊断及术后复发判断的价值。方法 收集2014年6月至2017年1月在合肥市第三人民医院就诊并确诊为CRS患者67例,作为CRS组。同时,严格筛选同期健康体检者109例作为对照组。采集空腹外周血进行白细胞、中性粒细胞、淋巴细胞计数。术后6个月再次对以上患者进行血细胞计数,并将患者分为术后复发组和术后非复发组,对CRS组、术后复发组、术后非复发组及对照组的上述血细胞指标进行分析。结果 CRS组白细胞计数（7.59±2.47）×10⁹/L、中性粒细胞计数（5.91±2.14）×10⁹/L及NLR水平（5.37±1.80）高于对照组,淋巴细胞计数（1.13±0.37）×10⁹/L低于对照组,差异均具有统计学意义（P<0.05）。ROC曲线分析显示,NLR预测CRS的最佳诊断值为4.37（95%CI：0.931～0.977,P<0.05）,ROC曲线下面积为0.954。方差分析表明,术后未复发组、对照组及CRS组3组间白细胞计数、中性粒细胞计数及NLR水平存在差异,差异具有统计学意义（P<0.05）。术后复发组白细胞计数（8.14±2.92）×10⁹/L、中性粒细胞计数（6.60±2.57）×10⁹/L及NLR水平（6.74±1.88）高于术后未复发组,淋巴细胞计数（1.00±0.36）×10⁹/L低于术后未复发组,差异均具有统计学意义（P<0.05）。结论 外周血NLR在CRS患者的诊断及术后复发评价中具有重要价值。     

70岁及以上非肥胖腹股沟疝患者临床路径预防性使用抗菌药物的临床效果

目的 探讨非肥胖腹股沟疝患者（≥70岁）围手术期是否使用预防性抗菌药物在临床路径（CP）中的效果。方法 选择合肥市第三人民医院普外科2017年2月至2019年12月CP中控制好合并症的76例非肥胖高龄腹股沟疝患者,按照随机数字表法,分为试验组（38例）与对照组（38例）。试验组患者不使用抗菌药物,对照组患者使用预防性抗菌药物。分析两组患者术后切口情况及相关指标。结果 试验组患者术后切口并发症发生率为7.89%,对照组为5.26%,两组差异无统计学意义（P>0.05）。两组患者术前白细胞计数[（5.52±1.28）×10⁹/L vs（5.73±1.59）×10⁹/L]、中性粒细胞比值[（63.91±6.55）% vs（63.77±9.18）%]、C反应蛋白（CRP）[（3.35±0.80）mg/L vs（3.30±0.79）mg/L]及最高体温[（36.59±0.44）℃ vs（36.62±0.36）℃]进行比较,差异无统计学意义（P>0.05）。两组患者术后白细胞计数[（5.98±1.37）×10⁹/L vs（6.11±1.66）×10⁹/L]、中性粒细胞比值[（65.22±6.49）% vs（64.98±9.09）%]、CRP[（7.47±0.85）mg/L vs（7.13±0.86）mg/L]及最高体温[（36.84±0.45）℃ vs（36.81±0.34）℃]进行比较,差异无统计学意义（P>0.05）。两组患者手术前后白细胞计数、中性粒细胞比值、CRP及最高体温差值进行比较,差异无统计学意义（P>0.05）。。结论 对于CP中控制好合并症的非肥胖高龄腹股沟疝患者,围手术期可以不使用预防性抗菌药物。     

磷酸西格列汀联合二甲双胍治疗初发型2型糖尿病患者的疗效

目的 分析初发型2型糖尿病患者采用磷酸西格列汀联合二甲双胍治疗的效果，为临床提高参考。方法 选取2014年6月至2016年6月黄冈市黄州区人民医院收治的初发型2型糖尿病患者90例为研究对象，依据随机数字表随机分为观察组和对照组，每组各45例，对照组采取二甲双胍治疗，观察组采用二甲双胍联合磷酸西格列汀治疗，两组患者均治疗12周，观察两组患者血糖、胰岛素抵抗指数以及血脂变化，分析两组患者治疗效果。结果 经过治疗，两组患者空腹血糖（FBG）、餐后2 h血糖（2 h PG）和糖化血糖蛋白（HbAlc）均显著降低，观察组患者[FBG（7.12±2.05）mmol/L、HbAlc（8.21±1.26）%、2 h PG（9.52±2.34）mmol/L]均低于对照组[FBG（9.36±2.05）mmol/L、HbAlc（8.27±1.69）%、2 h PG（13.10±2.37）mmol/L]，差异有统计学意义（P<0.05）。体质量指数、胰岛素抵抗指数均得到改善，观察组分别为（18.62±1.84）kg/m²、（13.25±2.36）mU/L，改善情况优于对照组[（21.65±2.05）kg/m²，（11.20±2.64）mU/L]，差异有统计学意义（P<0.05）。观察组总胆固醇、三酰甘油、低密度脂蛋白均低于对照组（P<0.05），高密度脂蛋白高于对照组（P<0.05）。观察组患者低血糖发生率2.2%，低于对照组的17.8%（P<0.05）。结论 磷酸西格列汀联合二甲双胍治疗初发型2型糖尿病患者疗效肯定，能更好地控制血糖和改善胰岛素抵抗。     

血清神经元特异性烯醇化酶缺血修饰蛋白与新生儿缺氧缺血性脑病严重程度的相关性分析

目的 探讨血清神经元特异性烯醇化酶（NSE）、缺血修饰蛋白（IMA）与新生儿缺氧缺血性脑病（HIE）病情严重程度的关系。方法 选择2016年3月至2017年2月潮州市中心医院新生儿科收治的81例HIE患儿作为HIE组,根据病情轻重,将HIE组分为轻度HIE组32例、中度HIE组24例及重度HIE组25例;选择同期30例正常足月新生儿作为对照组。分别检测对照组生后1~2 d及3组患者HIE急性期与恢复期血清NSE、IMA水平,分析两者与HIE病情严重程度的关系。采用Pearson相关分析,分析三组HIE急性期及恢复期NSE、IMA的相关性。结果 3组HIE急性期及恢复期NSE、IMA均高于对照组,差异有统计学意义（P<0.05）。其中重度HIE组急性期NSE、IMA[（61.14±30.8）μg/L,（97.26±2.46） U/mL]高于中度HIE组[（40.30±10.81）μg/L,（93.08±1.90） U/mL]及轻度HIE组[（18.75±1.40）μg/L,（83.75±0.78） U/mL],差异均有统计学意义（P<0.05）。恢复期重度HIE组NSE,IMA[（20.81±9.57）μg/L,（83.34±2.01） U/mL]及中度HIE组[（21.14±7.04）μg/L,（82.28±2.17） U/mL]均高于轻度HIE组[（10.89±5.14）μg/L,（73.17±1.91） U/mL],差异均有统计学意义（P<0.05）。Pearson相关性显示,三组患者HIE急性期,恢复期NSE与IMA均呈正相关（P<0.05）。结论 血清NSE与IMA水平的变化与HIE病情严重程度正相关。     

LiDCOrapid监测下目标导向血流动力学管理对老年胃肠手术患者术后转归的影响

目的 观察LiDCOrapid监测下目标导向血流动力学管理对老年胃肠手术患者术后转归的影响。方法 选择2018年2月至2019年7月入住安徽中医药大学第一附属医院的90例胃肠手术患者,采用随机数字表法分为LiDCOrapid监测下目标导向血流动力学管理组（L组）与经验麻醉组（E组）,每组45例。L组采用LiDCOrapid监护仪监测心脏指数（CI）、每搏量变异率（SVV）,以SVV（≤ 12%）、CI[≥ 2.5 L/（min·m²）]、平均动脉压（维持在基础值±20%）为目标,调整补液和心血管药物的使用;E组仅凭医师临床经验实施血流动力学管理。记录术中血流动力学相关指标,以及术后恢复和相关并发症发生情况。结果 L组患者术中液体输注总量为（859.16±178.61）mL、尿量为（257.83±149.22）mL,均少于E组,差异有统计学意义（P<0.05）。L组患者术后拔管时间和麻醉苏醒室留观时间分别为（25.29±10.63）min和（40.44±10.12）min,短于E组,差异有统计学意义（P<0.05）。L组患者术后首次通气时间、住院时间分别为（4.35±1.47）d和（11.91±1.89）d,均短于E组,差异有统计学意义（P<0.05）。L组患者术后第24小时血乳酸为（0.86±0.29）mmol/L,低于E组,差异有统计学意义（P<0.05）。结论 LiDCOrapid监测下的目标导向血流动力学管理,能够减少老年胃肠手术患者术中输液总量,加快术后胃肠功能恢复,缩短住院时间。     

Recent advances in the treatment of chronic hepatitis B

Introduction: At present, two strategies exist for the treatment of chronic hepatitis B (CHB): i) standard or pegylated interferon alpha (IFN) with mainly immune modulatory effects; and ii) nucleos(t)ide analogues (NA) with direct antiviral effects. The optimal treatment for an individual patient remains controversial.

Areas covered: The treatment efficacy and prediction of response to antiviral agents for chronic hepatitis B are reviewed and discussed.

Expert opinion: The rates of hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) loss or seroconversion are continuously increasing in CHB patients after stopping a finite course of IFN, whereas long-term NA therapy is usually required to improve the adverse outcomes of CHB. Lower baseline HBV DNA level is a strong predictor for both sustained viral suppression and HBeAg seroconversion in patients receiving IFN-based as well as NAs therapy. In addition, HBeAg-positive patients with genotype A or B infection have better responses to IFN-based therapy than those with genotypes C or D infection. Furthermore, on-treatment predictors such as declines of serum HBV DNA, HBsAg and HBeAg levels may be helpful in making decisions of subsequent therapy. Regarding the association of host genetic factors with responses to antiviral therapy, current evidence is limited.     

口服碳酸氢钠对慢性肾病进程的影响

目的探讨口服碳酸氢钠能否延缓慢性肾病(chronic kidney disease,CKD)肾功能下降的速率。方法 110例CKD患者随机分为碳酸氢钠组或安慰剂组,分别口服碳酸氢钠或安慰剂治疗2年,估算治疗前后肾小球滤过率(eGFR)下降的速率,eGFR快速下降[>3 mL.min 1.(1.73 m)2.y 1]和发展成终末期肾病(ESRD)患者人数[eGFR<10 mL.min 1.(1.73 m)2]比。同时测量血清白蛋白和饮食蛋白摄入。结果治疗2年后,与安慰剂组相比,碳酸氢钠组eGFR下降较慢(P<0.05),快速进展的患者少(P<0.05),发展成ESRD的患者也少(P<0.05)。碳酸氢钠组营养参数明显改善。结论碳酸氢钠可延缓CKD发展成ESRD的速率,且可改善CKD患者的营养状态。     

Comparison of the antidiabetic effects of linagliptin among groups with a normal renal function and a mild or severe renal impairment – retrospective observation study of Japanese patients with type 2 diabetes mellitus

Objective: The clinical course > 6 months after the initiation of linagliptin in patients with type 2 diabetes was compared among the groups divided by their renal function.

Methods: Two hundred and sixteen Japanese patients with type 2 diabetes treated with 5 mg once daily linagliptin were studied as the treated set. One hundred and forty-five subjects whose medications were not changed during the observation period were investigated as the full analysis set to assess the effectiveness. The subjects were divided into three groups based on an eGFR: eGFR ≥ 60, 59 – 45 and < 45 ml/min/1.73 m². The parameters were analyzed separately in the patients receiving monotherapy and additional therapy of linagliptin.

Results: The HbA1c (NGSP) levels significantly improved in both the patients receiving monotherapy and additional therapy. The changes in the HbA1c levels at 6 months were not significantly different between the groups with an eGFR ≥ 60, 59 – 45 and < 45 ml/min/1.73 m² receiving monotherapy (?1.0, ?0.8 and ?0.8%, respectively). Similarly, those were not significantly different between the different groups receiving additional therapy (?0.6, ?0.5 and ?0.7%, respectively).

Conclusions: Linagliptin is considered to be effective for patients with type 2 diabetes and renal impairment in the present analysis performed at our institution.     

基于肾功能情况的左氧氟沙星合理用药分析

目的 结合肾功能情况分析住院患者左氧氟沙星的用药合理性。方法 检索2016年7月1日-2017年6月30日住院部使用左氧氟沙星的病例,等距抽样法随机抽查200例进行详细分析。结果 男女各100例,年龄（69.1±17.3）岁,不合理用药43例,发生不良反应22例,多发于老年人和慢性肾功能不全患者。估算肾小球滤过率<50 mL·min^-1·（1.73 m²）^-1的患者31例,平均年龄（80.3±16.1）岁。超剂量给药30例,其中8例血肌酐仍在正常范围内。结论 左氧氟沙星仍未能很好地按照肾功能情况调整剂量,特别是高龄人群。临床药师可借助计算机系统开展多学科合作模式,提高左氧氟沙星的用药合理性。     

Discontinuation of Proton Pump Inhibitors in Patients With Chronic Kidney Disease

Purpose: Proton pump inhibitors (PPIs) are commonly used medications and are historically well tolerated. Recent studies have linked PPI use to the development of chronic kidney disease (CKD) and end-stage renal disease. This study investigated the impact of discontinuing PPIs on renal function in patients with CKD. Methods: We conducted a retrospective chart review of patients with established CKD, defined as 2 eGFR (estimated glomerular filtration rate) measurements of less than 60 mL/min/1.73 m² at least 90 days apart, who were on a PPI from January 1, 2014 to December 31, 2014, with a medication possession ratio greater than or equal to 70%. We compared baseline eGFR to a final eGFR after at least 6 months of discontinuation or continuation of a PPI. After power analysis, we targeted an enrollment of 200 patients (100 in each group) to achieve a power of 0.80 and an alpha of 0.05. Summary: A total of 97 patients in the PPI discontinuation group and 100 patients in the PPI continuation group met the study inclusion criteria. Baseline eGFR in the PPI continuation group was 47.9 mL/min/1.73 m² and 50.7 mL/min/1.73 m² in the discontinuation group. Final eGFR in the PPI continuation group was significantly higher than baseline at 51.1 mL/min/1.73 m² (+3.25 ± 12.8, P = .01). Final eGFR in the PPI discontinuation group was 51.8 mL/min/1.73 m² (+1.09 ± 12.8, P = .3). The average time between baseline and final eGFRs was 270 days in the PPI continuation group and 301 days in the discontinuation group. There was no statistically significant difference in the change in eGFRs between groups (95% confidence interval [CI] = −5.48-2.03, P = .37). Conclusions: Proton pump inhibitor discontinuation after prolonged continuous use in patients with CKD was not associated with a significant change in renal function after 1 year.     

Efficacy and safety profile of SGLT2 inhibitors in patients with type 2 diabetes and chronic kidney disease

ABSTRACT

Introduction: Sodium-glucose cotransporter type 2 inhibitors (SGLT2is) have a complex relationship with the kidney so that their use in patients with type 2 diabetes (T2DM) and diabetic kidney disease (DKD) has long been challenged.

Areas covered: SGLT2is in patients with DKD are discussed: renal mechanisms of action, PK/PD characteristics, clinical use in patients with stage 3 DKD, effects on estimated glomerular filtration rate (eGFR) and albuminuria, cardiovascular, and renal outcomes according to renal function, overall and renal safety, SGLT2is new place in updated guidelines.

Expert opinion: Whereas initial concerns (reduced glucose-lowering efficacy, early reduction in eGFR) led to restrictions in the use of SGLT2is in patients with DKD, recent positive observations have completely reversed the scene. Indeed, albuminuria is reduced and eGFR is preserved in the long term by SGLT2is. A significant reduction in cardiovascular events and hard renal outcomes was reported even in patients with eGFR 30–60 mL/min/1.73 m². The overall safety profile of SGLT2is is not altered in patients with mild to moderate DKD, with a reduced (rather than increased) risk of acute renal injury. This positive benefit/risk balance led recent guidelines to recommend SGLT2is in patients with T2DM and mild to moderate DKD, especially if albuminuria.     

Pharmacokinetics and pharmacodynamics of candesartan cilexetil in patients with normal to severely impaired renal function

Objective: We studied the pharmacokinetics and pharmacodynamics of single and multiple doses of candesartan cilexetil 8 mg per day in hypertensive patients with different degrees of renal function impairment. Candesartan is an angiotensin II subtype 1 (AT1) receptor antagonist that is administered orally as candesartan cilexetil which is converted in the active compound. Methods: Twenty-three patients were included, divided into groups according to creatinine clearance (cr cl. group A >60 nl · min⁻¹ · 1.73 m⁻², group B 30–60 ml · min⁻¹ · 1.73 m⁻² and group C 15–30 ml · min⁻¹ · 1.73 m⁻²). Results: Trough serum concentrations of candesartan were higher in group C compared with group A. The values did not increase after multiple dosing, indicating absence of accumulation. There was a significant negative correlation between the area under the concentration-time curve extrapolated to time infinity (AUC_inf) and the glomerular filtration rate (GFR) indicating a lower renal clearance of candesartan in patients with impaired renal function. The onset of haemodynamic and hormonal effects was gradual. During the single-dose study blood pressure as well as plasma renin activity (PRA) and angiotensin II were unchanged at peak. At day 5 of the multiple-dose study blood pressure was lower and both PRA and angiotensin II were higher compared with baseline. Conclusion: Although serum trough levels increased during repeated administration and half-life was higher in patients with impaired renal function, candesartan cilexetil at a dose of 8 mg per day does not lead to drug accumulation in these patients. This dose is effective in lowering blood pressure and appears to be suitable for patients with renal function impairment. Received: 3 August 1998 / Accepted in revised form: 19 October 1998     

Uric acid and incident chronic kidney disease in dyslipidemic individuals

Background: Elevated uric acid (UA) is a recognized risk factor for chronic kidney disease (CKD). This study aimed to investigate whether this association exists in dyslipidemic patients receiving multifactorial treatment.

Methods: An observational study conducted in Greece including 1,269 dyslipidemic individuals followed-up in a lipid clinic for ≥3 years. Estimated glomerular filtration rate (eGFR) was calculated by CKD-EPI equation and CKD was defined as ≤60?mL/min/1.73 m². The correlation was assessed between UA levels and the CKD risk after adjusting for potential confounding factors, after defining the following UA quartiles: Q1: ?6?mg/dL.

Results: After excluding patients with baseline eGFR <60?mL/min/1.73 m², gout and those taking UA-lowering drugs, 1,095 individuals were eligible; of those, 91% and 69% were treated with statins and anti-hypertensive drugs, respectively. During their follow-up (6 years; IQR?=?4–10), 11.9% of the subjects developed CKD, whereas the median annual eGFR decline was 0.69?mL/min/1.73 m² (IQR?=?0.45–2.33). Multivariate analysis showed that baseline UA levels (HR?=?1.26; 95% CI?=?1.09–1.45, p?=?.001), female gender (HR?=?1.74; 95% CI?=?1.14–2.65, p?=?.01), age (HR?=?1.10; 95% CI?=?1.07–1.12, p?p?=?.03), cardiovascular disease (HR?=?1.62; 95% CI?=?1.02–2.58, p?=?.04), decreased baseline renal function (eGFR <90?mL/min/1.73 m²) (HR?=?2.38; 95% CI?=?1.14–4.81, p?=?.02), and low-density lipoprotein cholesterol reduction (HR?=?0.995; 95% CI?=?0.991–0.998, p?=?.01) were associated with incident CKD. Additionally, patients with UA ≥6?mg/dL exhibited a higher risk of incident CKD compared with those in the lowest UA quartile (HR?=?2.01; 95% CI?=?1.11–3.65, p?=?.02).

Conclusion: Higher UA levels are correlated with a higher risk of incident CKD in dyslipidemic individuals taking multifactorial treatment.     

Worsening renal function,adverse clinical events and major determinants for changes of renal function in patients with atrial fibrillation: a Japanese multicenter registry substudy

Objective: To explore factors related to changing renal function and the prognostic effect of worsening renal function in patients with atrial fibrillation (AF).

Methods: The present substudy was based on the SAKURA AF Registry, a Japanese multicenter prospective observational registry that includes 3267?AF patients from 63 institutions in the Tokyo area. Worsening renal function was defined as an estimated glomerular filtration rate (eGFR) decrease equaling more than 20% of the patient’s baseline eGFR.

Results: During a median 39.3?month follow-up period, patients’ eGFR decreased annually by a mean value of 1.07?mL/min/1.73?m². Multivariable analysis showed that age ≥75?years, body weight ≤50?kg, a history of heart failure and initially preserved renal function (creatinine clearance [CrCl]?≥?60?mL/min) were significantly associated with a decrease in eGFR, whereas a history of AF ablation was associated with a maintain in eGFR. The 194 patients with worsening renal function were at significantly increased risk of death, stroke and major bleeding (adjusted hazard ratios [HRs]: 2.06, 1.97 and 2.23, respectively).

Conclusion: Age ≥75?years, body weight ≤50?kg, a history of heart failure and initially preserved renal function appear to promote renal dysfunction in patients with AF, but a history of AF ablation seems to have a favorable effect. Worsening renal function seems to increase AF patients’ risk of adverse clinical events. Renal function can decline quickly; thus, early intervention including AF ablation is warranted.     

Effect of telbivudine therapy on the cellular immune response in chronic hepatitis B

Weak T-cell reactivity to the hepatitis B virus (HBV) is believed to be the dominant cause of chronic HBV infection. Several lines of experimental evidence suggest that treatment with telbivudine increases the rate of HBV e antigen (HBeAg) loss, undetectable HBV DNA, and normalization of serum alanine aminotransferase (ALT) in chronic hepatitis B patients (CHB). However, it is still unclear how early antiviral therapy affects cellular immune responses during sustained telbivudine treatment. In order to investigate this issue, we measured detailed prospective clinical, virological, and biochemical parameters, and we examined the frequency of T cell subgroups as well as the ability of peripheral blood mononuclear cells (PBMC) to respond to stimuli at five protocol time points for 51 CHB patients who received telbivudine therapy for one year. The preliminary data from this study revealed that effective-treated patients showed an increased frequency of peripheral blood CD4⁺T lymphocytes, an augmented proliferative response of HBV-specific T-cells to the hepatitis B core antigen (HBcAg), and the induction of cytokines, such as interferon gamma (IFN-γ), tumour necrosis factor alpha (TNF-α) release at the site of infection compared to non-responsive patients. Enhanced HBV-specific T-cell reactivity to telbivudine therapy, which peaked at treatment week 12, was confined to a subgroup of effective-treated patients who achieved greater viral suppression.