利妥昔单克隆抗体不宜作为继发性难治性肾病的挽救治疗措施

背景　利妥昔单克隆抗体（RTX）用于肾小球疾病的治疗已近20年,近年来其在治疗原发性和继发性肾病方面积累了一些循证医学证据,但对于较为明显的肾功能不全患者是否适合应用RTX进行挽救性治疗,目前尚无相关研究。目的　观察RTX挽救性治疗继发性难治性肾病患者的有效性和安全性。方法　回顾性选取2018-2019年北京大学国际医院收治的所有住院使用RTX治疗的成年难治性肾病患者48例。根据原发病诊断结果将患者分为原发性肾病（PN）组和继发性肾病（SN）组,再将SN组依据RTX治疗前血肌酐（Scr）分为SN-NST亚组（Scr<300 μmol/L）和SN-ST亚组（Scr≥300 μmol/L）。收集所有患者的一般资料（包括性别、年龄、体质量、身高、体表面积、原发病）,RTX治疗前、后实验室检查结果〔24 h尿蛋白（Upro）、白细胞计数（WBC）、红细胞计数（RBC）、血小板计数（PLT）、白蛋白（Alb）、Scr、CD4+细胞计数〕,计算CD4+细胞计数/WBC比例,记录RTX治疗期间严重不良事件〔包括严重感染全身（应用抗生素≥7 d或联合应用2种及以上抗感染药物）、肾脏替代治疗（RRT）、多脏器功能衰竭综合征（MODS）、死亡等〕,RTX末次治疗后3个月肾脏转归情况（即是否行维持性血液透析）。结果　48例使用RTX治疗的难治性肾病患者均进行肾穿刺活检;PN组19例（39.6%）,SN-NST亚组14例（29.2%）,SN-ST亚组15例（31.2%）。SN-ST亚组患者年龄小于PN组和SN-NST亚组（P<0.05）。PN组患者RTX治疗前24 hUpro、RBC、PLT高于SN-NST亚组、SN-ST亚组,Alb低于SN-NST亚组、SN-ST亚组（P<0.05）;SN-ST亚组患者RTX治疗前Scr高于PN组、SN-NST亚组,CD4+细胞计数低于PN组、SN-NST亚组（P<0.05）。SN-ST亚组患者RTX治疗后Scr高于PN组、SN-NST亚组（P<0.05）。PN组、SN-NST亚组患者RTX治疗后24 hUpro较同组治疗前降低（P<0.05）。SN-NST亚组、SN-ST亚组患者RTX治疗后WBC较同组治疗前降低（P<0.05）。SN-ST亚组患者RTX治疗后RBC较同组治疗前升高（P<0.05）。PN组患者RTX治疗后PLT较同组治疗前降低,SN-ST亚组患者RTX治疗后PLT较同组治疗前升高（P<0.05）。PN组、SN-NST亚组患者RTX治疗后Alb较同组治疗前升高（P<0.05）。三组患者RTX单位时间体表面积的累积剂量比较〔PN组、SN-NST亚组、SN-ST亚组依次为（437±322）、（503±344）、（331±312）mg?月-1?（m2）-1〕,差异无统计学意义（F=1.048,P=0.359）。SN-ST亚组患者RTX治疗期间严重感染发生率、行RRT者比例及RTX末次治疗后3个月行维持性血液透析者比例高于PN组（P<0.05）;SN-ST亚组患者RTX治疗期间行RRT者比例、RTX末次治疗后3个月行维持性血液透析者比例高于SN-NST亚组（P<0.05）。结论　Scr≥300 μmol/L的继发性难治性肾病患者应用RTX治疗对其肾病改善作用不明显,且会明显增加其严重感染和肾衰竭发生风险,故RTX不应作为这部分患者的挽救治疗措施。     

无症状性脑梗死与睡眠障碍共病的研究进展

无症状性脑梗死（SBI）是指常无明确的卒中史、典型的临床症状及神经系统阳性体征,需通过颅脑影像学或尸检发现的脑梗死。随着研究的深入,SBI已被证实并非完全无症状,部分患者可能存在头晕、头痛、睡眠障碍、记忆力下降等非特异性神经功能损害表现。同时,大量临床报道显示,睡眠障碍是脑卒中后常见的并发症,并常会对患者的预后和生活质量产生不利影响。SBI作为脑梗死类型中的一种,与睡眠障碍也存在一定的联系,但由于SBI的临床特征,本身常被临床医生忽视,睡眠问题便更不受关注,国内外也缺乏相关研究报道。因此,本文对SBI与睡眠障碍共病的可能发生机制以及可能伴发的负面影响进行了综述,以便提高临床医生对其的关注度,做到早期诊治。     

百令胶囊联合来氟米特治疗慢性肾小球肾炎的临床研究

目的研究百令胶囊联合来氟米特片治疗慢性肾小球肾炎的临床疗效。方法选取2013年12月—2017年12月河南科技大学第一附属医院接收的100例慢性肾小球肾炎患者作为研究对象,将患者随机分为对照组和治疗组,每组各50例。对照组患者口服来氟米特片,2片/次,1次/d。治疗组患者在对照组基础上口服百令胶囊,4粒/次,3次/d。两组患者均持续治疗12周。观察两组患者的临床疗效,同时比较两组治疗前后的肾功能指标和尿液检查指标水平。结果治疗后,对照组和治疗组的总有效率分别为84.00%、96.00%,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者尿素氮(BUN)和血肌酐(Scr)水平均显著降低,同组治疗前后比较差异具有统计学意义(P0.05);治疗后,治疗组肾功能指标水平显著低于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者24h尿蛋白定量(24 hUpro)、尿β2-微球蛋白(β2-MG)和尿红细胞计数(RBC)水平均显著降低,同组治疗前后比较差异具有统计学意义(P0.05);治疗后,治疗组尿液检查指标水平显著低于对照组,两组比较差异具有统计学意义(P0.05)。结论百令胶囊联合来氟米特片治疗慢性肾小球肾炎具有较好的临床疗效,能显著改善患者肾功能和尿液检查指标,安全性较高,具有一定的临床推广应用价值。     

以大量蛋白尿、水肿为主要表现的乙型肝炎病毒相关性肾炎临床特征分析

[目的]探讨以大量蛋白尿、水肿为主要表现的乙型肝炎病毒相关性肾炎(HBV-GN)的临床特征,以提高对该病的认识。[方法]对我院近5年来收治的5例以大量蛋白尿、水肿为主要表现的HBV-GN患者的临床资料进行回顾分析,并结合文献进行复习。[结果]全部患者均有明显水肿和蛋白尿,3例有腹水,尿蛋白定量为3.58~7.50g/d,(平均5.42g/d),血浆白蛋白为20.4~28.2g/L(平均24.5g/L);4例表现为肾病综合征,1例为肾炎综合征;病理类型4例为膜性肾病,1例为局灶性节段性肾小球硬化。阿德福韦酯与泼尼松联合治疗取得了很好的近期疗效。[结论]以大量蛋白尿、水肿为主要表现的HBV-GN患者大多以肾病综合征、膜性肾病为主要表现,应早期给予抗病毒与糖皮质激素联合治疗。消化内科医师应不断提高对该病的认识,早诊早治,减少误诊。     

Meta-analysis of combined therapy for adult hepatitis B virus-associated glomerulonephritis

AIM: To investigate the efficacy and safety of combined antiviral and immunosuppressant therapy in adult hepatitis B virus-associated glomerulonephritis (HBV-GN) patients.METHODS: A computerized literature search was carried out in the PubMed database, Embase, the Cochrane Library, Chinese BioMedical Literature on disc, Chinese Medical Current Contents, Chinese National Knowledge Infrastructure, Wanfang and VIP (Chinese Technological Journal of Database) to collect articles between June 1980 and December 2010 on therapy with immunosuppressants, e.g., glucorticosteroids, mycophenolate mofetil and leflunomide, combined with antivirals, e.g., interferon, lamivudine, entecavir and adefovir dipivoxil, in adult HBV-GN patients. The primary outcomes were remission of proteinuria, clearance of HBV e-antigen, and elevation of serum albumin. The secondary outcomes were blood levels of alanine aminotransferase, serum creatinine, and HBV-DNA titer. Meta-analysis was performed using Review Manager 5.1. Fixed or random effect models were employed to combine the results after a heterogeneity test. The effects of the combined therapy were analyzed for different doses of glucorticosteroid and different types of HBV-GN.RESULTS: Twelve clinical trials with 317 patients were included. A significantly higher incidence of HBV-GN was found in male patients (relative risk = 2.40, 95% CI: 1.98-2.93). Combined therapy reduced the proteinuria significantly with a mean difference of 4.19 (95% CI: 3.86-4.53) and increased the serum albumin concentration significantly with a mean difference of -11.95 (95% CI: -12.97-10.93) without significant alterations of liver function (mean difference: 4.62, 95% CI: -2.55-11.79) and renal function (mean difference: 10.29, 95% CI: 0.14-20.45). No significant activation of HBV-DNA replication occurred (mean difference: 0.12, 95% CI: -0.37-0.62). There was no significant difference between the high dose glucorticosteroid group and the low dose glucorticosteroid group in terms of proteinuria remission (P = 0.76) and between different pathological types of HBV-GN [membranous glomerulonephritis (MN) vs mesangial proliferative glomerulonephritis, P = 0.68; MN vs membranoproliferative glomerulonephritis, P = 0.27].CONCLUSION: Combined antiviral and immunosuppressant therapy can improve the proteinuria in HBV-GN patients without altering HBV replication or damaging liver and renal functions.     

Asymptomatic pancreatic lesions: New insights and clinical implications

Despite great efforts in experimental and clinical research, the prognosis of pancreatic cancer (PC) has not changed significantly for decades. Detection of pre-invasive lesions or early-stage PC with small resectable cancers in asymptomatic individuals remains one of the most promising approaches to substantially improve the overall outcome of PC. Therefore, screening programs have been proposed to identify curable lesions especially in individuals with a familial or genetic predisposition for PC. In this regard, Canto et al recently contributed an important article comparing computed tomography, magnetic resonance imaging, and endoscopic ultrasound for the screening of 216 asymptomatic high-risk individuals (HRI). Pancreatic lesions were detected in 92 of 216 asymptomatic HRI (42.6%). The high diagnostic yield in this study raises several questions that need to be answered of which two will be discussed in detail in this commentary: First: which imaging test should be performed? Second and most importantly: what are we doing with incidentally detected pancreatic lesions? Which ones can be observed and which ones need to be resected?