中成药联合普利或沙坦类药物治疗糖尿病肾病的网状Meta分析＊

目的 运用网状Meta分析方法，以单纯ACEI/ARB（angiotensin receptor blockers，ARB；angiotensin-converting enzyme inhibitor，ACE）治疗为共同参照，对比海昆肾喜胶囊、黄葵胶囊、尿毒清颗粒、肾衰宁胶囊、雷公藤多苷片、金水宝胶囊、百令胶囊、火把花根片对糖尿病肾病的临床疗效。方法 计算机检索有关海昆肾喜胶囊、黄葵胶囊，尿毒清颗粒、肾衰宁胶囊、雷公藤多苷片、金水宝胶囊、百令胶囊、火把花根片联合ACEI/ARB治疗糖尿病肾病的随机对照试验。由2名研究人员独立筛选，包括质量、评估，数据采用R、Gemtc、ＲevMan 5.3软件进行网状Meta分析和传统Meta分析。最终纳入86篇RCTs，共7413例患者，涉及9种干预措施。结果 Meta分析结果显示：①在综合疗效方面，金水宝胶囊、雷公藤多苷片、肾衰宁胶囊联合ACEI/ARB排序靠前，其中雷公藤多苷片联合ACEI/ARB降低24 h尿蛋白（24 h UPQ）和尿微量蛋白（UAER）的疗效最佳，肾衰宁胶囊联合ACEI/ARB降低血肌酐（Scr）、糖化血红蛋白（HBA1C）和空腹血糖（FPG）的疗效最佳；②在安全性方面，联合中成药均较单纯ACEI/ARB治疗有一定改善，因临床异质性较大无法定量合并，所有纳入研究未发生严重不良反应。由于纳入文献质量相对偏低，得出的结论尚有待临床验证。结论 结合网状Meta分析结果和文献信息，在治疗有效率方面，金水宝胶囊联合ACEI/ARB疗效最优；在降低24 h尿蛋白（24 hUPQ）和尿微量蛋白（UAER）方面，均为雷公藤多苷片联合ACEI/ARB疗效最优；在降低血肌酐（Scr）、糖化血红蛋白（HBA1C）和空腹血糖（FPG）方面，均为肾衰宁胶囊联合ACEI/ARB疗效最优。     

滋阴活血汤治疗早期糖尿病肾病临床研究

目的:观察滋阴活血汤治疗早期糖尿病肾病的临床疗效。方法:选取130例早期糖尿病肾病患者,随机分为对照组和观察组,各65例。对照组给予降糖等西医对症治疗,观察组在对照组基础上给予滋阴活血汤,两组疗程均为4周。观察两组治疗前后血液流变学变化,采用全自动生化分析仪进行检测;核因子(nuclear factor,NF)-κB变化,采用双抗体夹心酶联免疫吸附试验测定;24小时尿蛋白变化,采用放射免疫法测定;两组治疗前后症状总积分变化。结果:治疗后,观察组治疗后全血黏度、红细胞压积比、纤维蛋白原水平均明显低于对照组(P0.05);观察组治疗后NF-κB及24小时尿蛋白水平均低于对照组(P0.05);观察组治疗后症状总积分明显低于对照组(P0.01);对照组有效率为81.5%,观察组为93.8%,组间比较,差异有统计学意义(χ~2=4.561,P0.05)。两组治疗中未见严重不良反应。结论:滋阴活血汤治疗早期糖尿病肾病疗效确切,安全;能有效改善患者血液流变学,降低NF-κB及24小时尿蛋白水平。     

Relationship between diabetic retinopathy and diabetic nephropathy; A longitudinal follow-up study from a tertiary care unit of Karachi,Pakistan

ObjectiveTo determine the development and progression of diabetic retinopathy in subjects with diabetic nephropathy.MethodologyThis retrospective longitudinal follow up study was conducted in outpatient department of Baqai Institute of Diabetology and Endocrinology (BIDE), a tertiary care diabetes unit of Karachi Pakistan, from January 2005 to December 2016. Type 2 diabetic subjects with newly diagnosed diabetic nephropathy (DN) and sex-age matched controls were identified from the electronic database of the institute, Health Management System (HMS). Subjects with type 1 diabetes, gestational diabetes and subjects with diabetic retinopathy (DR) at the baseline of both DN and non-DN group were excluded from the study. Statistical analyses were conducted by using SPSS version 20.ResultOut of 3056 type 2 diabetic subjects, 2389 were with DN and 667 were without DN. The incidence of retinopathy was found to be 21.7 per 1000 person years. The incidence rate ratio (IRR) of 2.57 (1.92–3.43) showed that retinopathy was significantly higher in subjects with DN as compared to subjects without DN. Kaplan-Meier survival plot confirmed that subjects with DN had a worse diabetic retinopathy-free survival than subjects without DN.ConclusionDiabetic nephropathy is an independent risk factor for the development and progression of diabetic retinopathy.     

Serum anti-phospolipase A2 receptor antibodies and glomerular IgG4 in the diagnosis of membranous nephropathy

Objective To discuss the relationship between serum anti-Phosphalipase A2 receptor (PLA2R) antibodies and glomerular IgG4 subclass in patients with membranous nephropathy and evaluate the diagnostic value of the two markers. Methods Patients diagnosed as membranous nephropathy from October 2011 to April 2014 in Peking Union Medical College Hospital were included and divided into IMN and SMN groups accoding to their clinical diagnosis. Serum anti-PLA2R antibodies and glomerular IgG subclasses were both detected by indirect immunofluorescence assay. Receiver operator characteristic curves were used to evaluate the diagnostic efficiency of anti-PLA2R antibodies and glomerular IgG4. Results Prevalence of serum anti-PLA2R antibodies of IMN patients was 69.5% (41/59); prevalence of MLN patients was 4.8% (1/21). Within the IMN group, thirty-five patients showed positive results of both serum anti-PLA2R antibodies and glomerular IgG4; Six patients were positive for serum anti-PLA2R antibodies but negative for glomerular IgG4; Seventeen patients were positive for glomerular IgG4 but negative for serum anti-PLA2R antibodies; one patient was negative for both tests. The sensitivity of serum anti-PLA2R antibody was 69.5% and the specificity was 95.2%; the sensitivity of glomerular IgG4 was 89.8% and the specificity was 52.3%. The sensitivity of the combined marker consisting of serum anti-PLA2R antibody and glomerular IgG4 was 59.3% and the specificity was 100%. Four out of the six patients secondary to HBV infection, one out of the three patients secondary to Sjögren syndrome, one out of the three patients secondary to malignant tumor showed positive results of serum anti-PLA2R antibodies. Conclusions Serum anti-PLA2R antibodies were of high prevalence among IMN patients; the prevalence among SMN patients varied with etiologies. Results of serum anti-PLA2R antibodies and glomerular IgG4 were helpful to rule out secondary etiologies in the diagnosis of membrnous nephropathy.     

黄芪和山药配伍微粉对糖尿病肾病大鼠抗氧化能力的影响

目的:观察黄芪和山药配伍微粉对糖尿病肾病大鼠抗氧化能力的影响,探讨其保护大鼠肾功能的作用机制。方法:采用单侧肾脏切除合并腹腔注射链脲佐菌素的方法诱导建立糖尿病肾病大鼠模型,将造模成功的45只大鼠随机分为模型对照组12只、卡托普利组11只、微粉低剂量组11只和微粉高剂量组11只,另取10只作为假手术对照组。卡托普利组灌胃卡托普利溶液剂量为13.5 mg·kg-1,微粉低剂量组灌胃微粉溶液,剂量为5.4 g·kg-1,微粉高剂量组灌胃微粉溶液,剂量为10.8 g·kg-1,假手术对照组和模型对照组大鼠灌胃等容积蒸馏水,每日1次,连续给药6周。给药结束后,采用免疫浊度法于计算24 h尿微量白蛋白量,运用全自动生化仪测定血清血尿素氮(Blood urea nitrogen,BUN)、血肌酐(Serum creatinine,Scr)含量,采用黄嘌呤氧化酶法测定血清超氧化物歧化酶(Superoxide Dismutase,SOD)活性,硫代巴比妥酸法测定血清丙二醛(malonaldehyde,MDA)含量。结果:微粉高剂量组能明显改善糖尿病肾病大鼠的一般状况,体质量较模型对照组明显增加,肾脏肥大指数明显减小,差异具有统计学意义(P0.05)。与假手术组比较,模型对照组大鼠24 h尿蛋白定量、血清BUN、血清Scr均明显升高,微粉高剂量组和卡托普利组较模型对照组降低,差异具有统计学意义(P0.05)。与假手术组比较,模型对照组血清SOD活性明显降低,血清MDA含量明显升高,微粉高剂量组和卡托普利组与模型对照组比较,血清SOD活性升高,血清MDA含量降低,差异具有统计学意义(P0.05)。结论:黄芪和山药配伍微粉可明显降低糖尿病肾病大鼠尿蛋白的排泄,降低血清BUN和Scr水平,升高血清SOD活性,降低MDA含量,具有明显的肾脏保护作用,黄芪和山药微粉对糖尿病肾病大鼠肾脏的保护作用与提高抗氧化能力有关。     

探讨血清视黄醇结合蛋白和胱抑素C在肾脏疾病中的诊断价值

目的：探讨血清视黄醇结合蛋白（retinol blinding protein ,RBP）和胱抑素C（Cystatin C ,CysC）联合检测在肾脏疾病中的临床诊断价值。方法采用Beckman‐Coulter全自动生化仪分别检测173例肾病患者和50例健康体检者的血清尿素氮（U‐rea）、肌酐（Cr）、尿酸（UA）、视黄醇结合蛋白（RBP）、胱抑素C（CysC）的含量,并进行相关的统计学分析。结果173例肾病患者的RBP浓度为（70．86±14．41）mg／L ,CysC浓度为（3．41 ± 0．65）mg／L ,对照组RBP浓度为（41．36±5．68）mg／L ,CysC浓度为（0．98 ± 0．20）mg／L ,肾病组明显高于对照组（P＜0．05）。各疾病组 Cysc的检出阳性率最高,RBP次之,二者联合检测阳性率更高,明显高于传统肾功能指标Urea、Cr、UA。结论血清视黄醇结合蛋白和胱抑素C可作为诊断肾脏疾病的敏感指标,二者联合检测可提高诊断阳性率。     

Efficacy of mizoribine followed by low-dose prednisone in patients with idiopathic membranous nephropathy and nephrotic-range proteinuria

Abstract

Background: Idiopathic membranous nephropathy (IMN) patients with persistent high-grade proteinuria are at the highest risk for developing end-stage renal failure. We previously reported the effects of treatment with mizoribine followed by low-dose prednisone treatment in 4 IMN patients. The purpose of the present study was to further assess the effects of this combined treatment in a larger study group. Method: Thirteen patients with IMN and nephrotic-range proteinuria received combined treatment. Mizoribine was initiated at a dose of 150?mg/day, and 2–3 months later, 20?mg/day prednisone was added to the mizoribine regimen. The dosage of prednisone and/or mizoribine was tapered according to the urinary protein-to-creatinine ratio (P/C). We evaluated patient responses for up to 12 months after the initiation of combination therapy. Results: Before treatment, patient urinary P/C ranged from 3.7 to 15.9?g/g. Although these values did not decrease during mizoribine monotherapy, all patients showed dramatic P/C decreases over the course of combination therapy. At 3, 6, and 12 months after combination therapy, 15%, 31%, and 62% of patients attained complete remission, respectively, and all patients were in partial or complete remission 6 months after combination therapy. No notable side effects were observed. Conclusion: The addition of prednisone after mizoribine monotherapy can be beneficial for all IMN patients with nephrotic-range proteinuria syndrome. The risks associated with immunotherapy can be decreased by initially prescribing mizoribine alone, which might act as a base for establishing therapy, followed by low-dose prednisone treatment.