环孢素A联合小剂量激素治疗特发性膜性肾病31例临床分析

目的特发性膜性肾病(IMN)是肾病综合征的主要病理类型之一,因其对激素不敏感而易于成为难治性肾病综合征,本文通过观察环孢素A+小剂量激素治疗IMN的临床疗效,探讨其治疗。方法观察31例经肾活检证实诊断的IMN患者对环孢素A(CsA)+小剂量激素的治疗反应。治疗方法为环孢素A2～3mg·kg-1·d-1(CsA血药浓度120～150mg/L)8周,继以1～2mg·kg-1·d-1(CsA血药浓度80～100mg/L)维持12～24个月;泼尼松给予0.25mg·kg-1·d-1开始,8周后每2周逐渐减量至0.125mg·kg-1·d-1维持。观察尿蛋白排出量、血浆蛋白和症状体征。结果完全缓解率52%,部分缓解率35%,未缓解13%,有效率达87%。结论环孢素A联合小剂量激素治疗IMN疗效肯定。     

Efficacy of cyclosporin in difficult-to-treat idiopathic membranous nephropathy

SUMMARY: Poor tolerance and the potential long-term toxicity have limited the widespread use of corticosteroids and cytotoxic drugs in the treatment of idiopathic membranous nephropathy (IMN). Cyclosporin A (CyA) has been proven to be a less toxic alternative, but its efficacy needs further confirmation. Cyclosporin A (2–3mg/kg per day) in combination with low-dose methylprednisolone (4mg/day) was given to 28 nephrotic patients with IMN who had failed to respond, or tolerate, or to complete treatments with steroids and/or cytotoxic drugs. the mean duration of treatment was 11 ± 7 months. Seven patients (25%) showed a complete remission of proteinuria, 17 (60%) a partial one, and four (15%) did not respond at all. the average time to achieve optimal remission was 4.2 ± 1.4 weeks following the initiation of therapy. In those who responded completely or partially, plasma creatinine (Per) did not change significantly from pre CyA levels during follow up (1.0 ± 0.3 vs 1.2 ± 0.3mg/dL, P =NS). the remaining four patients who had renal insufficiency already before CyA (mean Per: 2.1 ± 0.8mg/dL), showed a rapid deterioration of renal function after the initiation of CyA (mean Per: 3.1 ± 1.5 mg/dL, P <0.01), and as a consequence, the drug was discontinued. A mul-tivariate analysis on the clinical and histological features demonstrated that the degree of renal function impairment ( P <0.02), the percentage of obsolete glomeruli ( P <0.01), and the severity of interstitial fibrosis ( P <0.005) independently predicted the response to therapy. Low dose CyA is an effective and safe alternative treatment for patients with IMN and normal renal function. However, the drug should be given with caution to patients with established renal insufficiency.     

Cytotoxic therapy for membranous nephropathy and renal insufficiency: improved renal survival but high relapse rate.

BACKGROUND: Patients with idiopathic membranous nephropathy (iMN) and renal insufficiency have a high risk for progression to end-stage renal disease (ESRD). In the short term, treatment with oral cyclophosphamide and steroids attenuates the deterioration of renal function in these patients; however, the long-term efficacy is unknown. METHODS: We have studied prospectively 65 patients with iMN and renal insufficiency (serum creatinine >135 micromol/l) who were treated with oral cyclophosphamide (1.5-2.0 mg/kg/day for 12 months) and steroids (methylprednisolone pulses 3 x 1 g, i.v. at months 1, 3 and 5, and oral prednisone 0.5 mg/kg/48 h for 6 months). RESULTS: Follow-up was 51 (5-132) months. Renal function temporarily improved or stabilized in all patients. A partial remission (PR) occurred in 56 patients followed by a complete remission (CR) in 17. During follow-up, 11 patients had relapsed (28% relapse rate after 5 years), of whom nine were re-treated because of renal function deterioration. At the end of follow-up, 16 patients were in CR, 31 in PR, eight had a persistent nephrotic syndrome, one had mild proteinuria, four had progressed to ESRD and five had died. Overall renal survival was 86% after 5 years and 74% after 7 years, compared with 32% after 5 and 7 years in a historical control group. Treatment-related complications occurred in two-thirds of patients, mainly consisting of bone marrow depression and infections. One patient has developed bladder cancer, another patient prostate cancer. CONCLUSIONS: Renal survival is good if patients with iMN and renal insufficiency are treated with oral cyclophosphamide. However, side effects occur frequently and relapse rate is high during longer follow-up.     

HLA-DRB and -DQB1 alleles in Polish patients with hepatitis B associated membranous nephropathy

Abstract: We have studied the HLA-DRB and -DQB1 alleles of 42 paediatric patients who have suffered from membranous nephropathy associated with a hepatitis B infection (HBVMN). These patients were all from the Gdansk area of Northern Poland and the disease was diagnosed by light and electron microscopy. The control population consisted of 55 healthy children, approximately age matched, from schools in Gdansk. In addition we have also analysed 40 patients chronically infected with hepatitis B, without any renal involvement, as hepatitis B disease controls. The HLA alleles were defined using PCR/SSP. As idiopathic membranous nephropathy and low responsiveness to hepatitis B vaccine have been found to be associated with DR3 in Caucasoids, our hypothesis was that the HBVMN patients would show an increase in DR3. Our results indicate that, although there is a small increase in the frequency of DRBl*0301 in the HBVMN patients (16/42 38%) when compared to the healthy controls (15/55 31%), this does not approach significance. There is a significant increase in the frequency of DQBl*0303 in the HBVMN patients vs the healthy controls, after correction for the number of antigens detected ( P ) (13/42 vs 2/55, RR=11.6, P =0.0007, P _c=0.02). A similar increase in DQBl*0303 is seen in the HBVMN patients when compared to the hepatitis controls (13/42 vs 4/40) but this is only significant before correction (RR=4.3, P =0.04).     

下腔静脉膜性梗阻的手术治疗

下腔静脉肝段膜性梗阻是一种罕见的临床病征。多数病人在下腔静脉肝段有一定长度的阻塞。最后诊断须藉腔静脉造影才能确定,下腔静脉膜性梗阻有时并发肝静脉阻塞,在外科处理上存在很多问题。各种旨在把门脉血流引入下腔静脉的门体分流术显然不仅无效,甚或是禁忌证。经右心房施行下腔静脉隔膜切开术仅部分患者适用。目前,对多数患者说施行脾肺固定术作门肺分流较为有效。1983年Ono等用脾肺固定术治疗19例MOVC病人,效果良好,术后所有病人无食管曲张静脉复发出血,除1例外,其余18例未再出现腹水。通过初步临床实践,这种手术对MOVC是一种安全、有效的疗法,因此,我们加以推荐。     

Cytochrome P4501B1 mutations cause only part of primary congenital glaucoma in Ecuador

Purpose: To determine the role of cytochrome P4501B1 ( CYP1B1 ) mutations in causing primary congenital glaucoma (PCG) in a cohort of Native Americans from Quito, Ecuador. Materials and methods: Seventeen patients with PCG from 15 Native American families were recruited from the Ophthalmology Clinic at Hospital Metropolitano, Quito, Ecuador. Experienced ophthalmologists examined all affected study subjects. Purified DNA was prepared from peripheral blood samples and CYP1B1 coding exons (exons 2 and 3) were amplified and sequenced. Southern blot was performed only on those affected patients who showed no mutations in the CYP1B1 coding exons. Results: The molecular basis of PCG in two families was determined: two novel mutations (a deletion and a point mutation) and one novel polymorphism in CYP1B1 were identified in addition to a previously described single amino acid substitution. Southern blot analyses on whole genomic DNA from affected individuals in whom no mutations were identified by the direct PCR/sequencing approach did not detect any large rearrangements or mutations outside the coding region. Conclusion: These findings suggest that mutations in CYP1B1 are not a major cause of PCG in this population and that at least one additional locus for this condition is responsible for most cases. Further, the PCG phenotype did not correlate readily with the molecular basis of the disorder, suggesting that careful clinical analysis of the phenotype cannot predict the molecular basis of the disease with accuracy.     

Management of idiopathic membranous nephropathy

Importance of the field: Idiopathic membranous nephropathy (IMN) can have a variable natural course. Treatments able to induce remission can improve the long-term prognosis. However, the optimal therapy for IMN remains controversial.

Area covered in this review: We reviewed the historical and current literature from 1979 to 2010 regarding the natural course of IMN and the possible treatments giving special emphasis to randomized controlled trials and to more recent approaches.

What the reader will gain: The reader will gain a comprehensive review of the available treatments of IMN. A personal therapeutic algorithm for nephrotic patients with IMN is also provided.

Take home message: At least five different treatments showed efficacy in many (but not all) patients with IMN.     

特发性膜性肾病中医证型与临床相关因素分析

目的探讨特发性膜性肾病(IMN)中医证型与病理类型、临床生化指标的关系。方法将113例IMN患者进行辨证分型、肾脏病理分期及临床生化指标检测,并分析其间关系。结果 IMN的证型以气阴两虚证(42.5%)和脾肾气虚证(35.4%)为主,兼证以湿热证(25.7%)和瘀血证(23.9%)为主;脾肾气虚与脾肾阳虚证病理多见于Ⅰ、Ⅱ期;气阴两虚证除见于Ⅰ、Ⅱ期外,也见于Ⅲ和Ⅳ期。气阴两虚证患者24 hUpro、LDL值较高(P0.05),ALB较低(P0.05);脾肾阳(气)虚证患者血Scr水平较肝肾阴虚证高(P0.05),较气阴两虚证低(P0.05);肝肾阴虚证患者ALB水平较高(P0.05)。结论 IMN的中医证型与其病理类型、临床生化指标有一定关系,结合病理和生化改变有助于IMN微观辨证。     

细胞骨架蛋白巢蛋白在人肾足细胞中的表达及意义

目的 检测细胞骨架蛋白巢蛋白在成人正常及病理状态肾组织中的表达,并观察其表达水平与患者尿蛋白的关系,初步探讨巢蛋白与足细胞损伤的关系.方法 正常对照肾组织(外科手术切除)6例,应用免疫组织化学(SP法)和免疫电镜检测巢蛋白的表达;病理状态肾组织:IgA肾病(无蛋白尿,电镜观察无足突融合,IrA-np)4例;IgA肾病(有蛋白尿,IgA-P)17例;膜性肾病8例;局灶性节段性肾小球硬化3例.应用免疫组织化学及即时RT-PCR的方法检测巢蛋白在肾组织中的表达并进行半定量、定量分析,与患者尿蛋白水平进行比较,分析两者之间相关关系.结果 巢蛋白表达在成人正常肾组织的足细胞初级足突中;免疫组织化学半定量及即时RT-PCR结果显示:IgA-np中巢蛋白的表达水平与正常肾组织差异无统计学意义;IgA-P、局灶性节段性肾小球硬化、膜性肾病中,巢蛋白的表达比正常肾组织显著降低(P<0.05),并与24 h尿蛋白呈负相关(r=-0.43,P<0.05).结论 巢蛋白在足细胞中低表达与肾小球中足细胞的损伤有关.