红斑狼疮肾损害诊治进展

狼疮肾炎的病理分型是临床诊治及预后判断的基础。狼疮肾炎的治疗策略与进展更是建立在不断累积的循证医学证据之上。增生性狼疮肾炎因其相对较差的预后而更受关注,其治疗强调序贯使用诱导与维持治疗。经济条件许可,可考虑把MMF与环磷酰胺一样作为活动性狼疮肾炎诱导治疗的一线选择用药,而其他新型免疫制剂的疗效尚缺乏足够证据。维持治疗目前推荐硫唑嘌呤或MMF。部分难治性狼疮肾炎可以尝试其他治疗方法,但疗效都不确定。     

钙神经调节蛋白抑制剂对狼疮性肾炎治疗作用的Meta分析

目的 系统评价钙神经调节蛋白抑制剂环孢素A和他克莫司治疗狼疮性肾炎的临床治疗作用.方法 采用Cochrane系统综述方法,检索时间截至2010年5月,检索范围包括www.guideline.gov,www.nice.org.uk,mdm.ca/cpgsnew/cpgs/index.asp,www.show.scot.nbs.uk,www.nzgg.org nz,www.eguidelines.c o.uk,www.-n.net,Cochrane图书馆、EMBASE、MEDLINE、万方数据库,中国期刊全文数据库,重庆维普中文科技期刊数据库,同时手工检索了相关杂志、专业资料和网络信息,对同质资料进行研究.采用Cochrane协作网提供的RevMan4.2软件进行Meta分析.结果 共检索出符合纳入标准的共7篇随机对照试验(RCT),其中环孢素A与环磷酰胺(CTX)治疗对照的RCT4篇,他克莫司与CTX治疗对照的RCT3篇.无论是环孢素A治疗组还是他克莫司治疗组,24 h尿蛋白量均有明显下降.与CTX治疗组比较,他克莫司治疗组24 h尿蛋白下降量差异有统计学意义(Z=2.8,P=0.005),但环孢素A治疗组差异无统计学意义(Z=1.08,P=0.28).他克莫司治疗组完全缓解率大于CTX治疗组(Z=3.64,P=0.0003),不完全缓解率两组差异无统计学意义(Z=0.53,P=0.6),总有效率他克莫司治疗组优于CTX治疗组(Z=2.2,P=0.03).结论 钙神经调节蛋白抑制剂能明显降低狼疮性肾炎患者24 h蛋白尿,且他克莫司的疗效优于CTX,但可靠的结论 仍需要大样本、多中心、设计良好的RCT的进一步验证.

Abstract：

Objective To systematically evaluate the clinical effects of cyclosporine A(CsA)and tacrolimus,which are calcineurin inhibitors,on lupus nephritis.Method In this study,the clinical trials on treatment of lupus nephritis with cyclosporine A and tacrolimus published until May 2010 were searched at www.guideline.gov, www.nice.org.uk, mdm.ca/cpgsnew/cpgs/index.asp, www.show.scot.nhs.uk,www.nzgg.org.nz,www.eguid elines.co.uk,www.gin.net, Cochrane library, EMBASE, MEDLINE,Wanfang database,Chinese Journal full-text Database,Chongqing Weipu Database by using the methods of Cochrane systematic review.At the same time the information from related journals,professional data and network were hand-searched.The homogeneous evaluation was performed by meta-analysis.Statistical analysis of clinical data was performed by using RevMan 4.2 software provided by the Cochrane Collaboration.Result A total of 214 reports were found,while only 7 randomized controlled trials met the inclusion criteria,4 of them were on the treatment with CsA(treatment group)and cyclosporine(CTX)group(control group),and 3 of them were the on treatment with FK506(treatment group)and CTX group(control group).There were 148 reports in the treatment of CsA and CTX group,while 185 reports in the treatment of FK506 and CTX group.Both CsA and tacrolimus group could decrease daily urinary protein.Tacrolimus group was good at reducing daily urinary protein as compared with CTX group,and the difference was statistically significant (Z = 2.8 ,P = 0.005),but there was no significant difference between CsA and CTX groups(Z = 1.08 ,P =0.28).Tacrolimus group was good at complete remission as compared with CTX group(Z = 3.64,P =0.0003),partial remission was similar in both groups(Z = 0.53,P = 0.6),and tacrolimus group was good at total remission(Z =2.2,P =0.03).There was no significant difference between CsA and CTX group in side effect within a short period,while FK506 had less side-effect than CTX group.Conclusion Compared with the treatment with CTX,tacrolimus was good at reducing daily urinary protein.CsA and CTX were similar in reducing daily urinary protein in the treatment of lupus nephritis.Tacrolimus resulted in better total remission than CTX and had less side effect.CsA and CTX groups were similar in side effect.On the whole,calcineurin inhibitor could significantly decrease daily urinary protein,and tacrolimus was better in treatment and had less side- effect than CTX.However,large scale,multicenter,well-designed clinical trials should be adopted to further confirm the conclusions.     

儿童肾小管间质性肾炎诊治进展

近年来,大量动物实验和人类肾小球疾病临床病理研究发现,肾小球疾病的发展和预后不仅与肾小球本身的损害有关(肾小球上皮、内皮细胞损伤、系膜细胞增殖、细胞外基质堆积、肾小球硬化等),更与其肾小管-间质病变的严重程度密切相关.     

Intermittent intravenous cyclophosphamide therapy for lupus nephritis

We carried out a preliminary study to determine whether intermittent intravenous cyclophosphamide therapy could be safely and effectively used in the treatment of childhood lupus nephritis. Sixteen children (4 to 18 years of age) with lupus nephritis were treated with cyclophosphamide monthly for 6 months and then every 3 months. Eight children were treated because of corticosteroid-unresponsive active lupus nephritis, with a fall in their creatinine clearance to less than 100 ml/min/1.75 m2, and eight children were treated because of corticosteroid-dependent nephrotic syndrome or active lupus nephritis with unacceptable corticosteroid-induced side effects. Cyclophosphamide treatment was associated with significant improvement at 1 year in mean levels of hemoglobin (11.3 +/- 0.5 to 13.1 +/- 0.3 gm/dl), C3 (52 +/- 5.9 to 108 +/- 13.7 mg/dl), and C4 (7.6 +/- 0.9 to 15.9 +/- 2.2 mg/dl) (all p less than 0.005), despite a significant reduction in mean prednisone dosage (31 +/- 5 to 14 +/- 2 mg/day; p less than 0.005). There was a decrease in 24-hour urine protein excretion from 3121 +/- 913 to 1016 +/- 364 mg/24 hours (p less than 0.05). For children whose initial creatinine clearance was less than 100 ml/min/1.75 m2, creatinine clearance also improved significantly (57.5 +/- 11 to 121 +/- 24.5 ml/min/1.75 m2; p less than 0.05). The long-term safety of intravenous cyclophosphamide therapy and its long-term efficacy in comparison with prednisone alone remain to be established. In the interim, intravenous cyclophosphamide therapy should be reserved for children with severe, unacceptable corticosteroid side effects or with corticosteroid-resistant and potentially life-threatening disease.     

Current topics in childhood lupus nephritis

Lupus nephritis is a major predictor of the prognosis of systemic lupus erythematosus (SLE). The present paper discusses lupus nephritis from clinical and immunopathological points of view. Although recent advances in diagnosis and treatment improve the prognosis of children with SLE, there remain many unsolved clinical problems. One of the current topics in the treatment for SLE is intermittent intravenous cyclophosphamide therapy which is effective even for the steroid-resistant patients with severe lupus nephritis, at least for short-term observation. Immunopathologically, the following issues are discussed: (i) The C5b-9 terminal complement complex plays an important role in the pathogenesis of lupus nephritis. The possible interaction of vitronectin and SP-40,40 is also mentioned; (ii) A semi-quantitative analysis of the charge barrier of the glomerular basement membrane reveals that the charge barrier dysfunction plays an important role in the pathogenesis of proteinuria in lupus nephritis. This study also demonstrates that the charge of immune deposits is important for the initiation of glomerular injury in lupus nephritis; (iii) It is demonstrated that the histopathological diversity of lupus nephritis is based on biological properties of nephritogenic autoantibodies in murine lupus models.     

Sex differences in childhood lupus nephritis

The renal status of 60 children (15 male and 45 female) with systemic lupus erythematosus seen over a 21-year period was evaluated clinically and by renal biopsy. The occurrence of serious clinical renal disease at initial observation, more severe renal impairment at outcome, and diffuse proliferative lupus nephritis were more common in male than in female patients. Although lupus is relatively uncommon in male subjects, our epidemiologic study shows that there is a sex difference in the severity of lupus nephritis, with male subjects being more severely affected than female subjects.     

Modern therapeutic strategies for paediatric systemic lupus erythematosus and lupus nephritis

There is still a significant morbidity and mortality associated with childhood‐onset systemic lupus erythematosus (SLE), despite an increasing armamentarium of immunosuppressive agents. The ideal therapeutic strategy for children and adolescents with SLE should provide the right amount of treatment to allow normal growth, development and fertility while reducing the disease activity and damage that can be accrued over the years. Each patient should have individualized treatments tailored to their organ involvement, disease severity and history of flares together with recent clinical, haematological and immunological parameters to avoid further flares of disease activity and side‐effects of treatment, especially severe infections and future malignancies. The most commonly cited side‐effects of medications include Cushingoid features of corticosteroids, infective complications of cyclophosphamide and gastrointestinal side‐effects of mycophenolate mofetil. There is increasing evidence to support the use of oral mycophenolate mofetil as opposed to cyclophosphamide for both induction and maintenance therapies in many children with SLE with or without lupus nephritis (LN). Recently, case series utilizing B‐lymphocyte depletion therapies with rituximab look promising for patients with severe or refractory disease activity. In this article, we explore current evidence to effectively treat children and adolescents with SLE with or without LN. Conclusion: Modern therapeutic strategies include reduced doses and use of corticosteroids and intravenous cyclophosphamide respectively, with increased use of azathioprine, MMF and rituximab.     

Improvement in lupus nephritis following treatment with a Chinese herbal preparation.

OBJECTIVE: To study the effect of a Chinese herbal decoction (CM), which contained 21 different herbs, on clinical remission in a patient with lupus nephritis and chronic nephrotic syndrome. DESIGN: Case report describing the clinical and laboratory markers of lupus activity in the patient before and after treatment with CM. We also studied the in vitro effect of CM and its hydrophobic extract on spontaneous IgG production by peripheral blood mononuclear cells (PBMCs) from 12 patients with systemic lupus erythematosus (SLE) compared with 9 healthy control subjects. RESULTS: Spontaneous PBMC IgG production was significantly higher in patients with SLE (mean +/- SD, 20.4+/-10.6 x 10(-5) g/L) compared with controls (4.7+/-1.9 x 10(-5) g/L) (P<.001). Addition of CM and its hydrophobic extract to PBMCs from patients with SLE resulted in significant suppression of spontaneous IgG production. CONCLUSIONS: The CM may contain some active pharmacological compound with immunosuppressive properties useful in the treatment of SLE. Further controlled studies are important to evaluate the efficacy of this medicine, potential toxic effects, and the possible immunosuppressive mechanisms of the active component(s).     

儿童系统性红斑狼疮治疗进展

系统性红斑狼疮 (ｓｙｓｔｅｍｉｃｌｕｐｕｓｅｒｙｔｈｅｍａｔｏｓｕｓ ,ＳＬＥ)以全身血管和结缔组织的广泛炎症为特征 ,常常存在抗核抗体 (ＡＮＡｓ) ,特别是存在抗双链ＤＮＡ (ｄｓ ＤＮＡ)抗体。临床表现多样 ,除发热、皮疹等共同表现外 ,因受累器官不同而表现不同。常常先后或同时累及泌尿、神经、心血管、血液、呼吸、消化、关节等多个器官系统。如不积极治疗 ,病情会逐渐进展 ,预后严重。ＳＬＥ的病因及发病机制尚不清楚 ,大量研究表明其发病是在遗传易感素质的基础上 ,在多种因素如免疫调节功能紊乱、激素水平失衡以及环境因素 (…