三种实验性IgA肾病模型的比较

目的探讨建立一种理想的IgA肾病（IgAN）动物模型方法。方法分别采用葡聚糖G200、大肠杆菌外膜蛋白和金葡菌的细胞膜20肽抗原决定簇诱导小鼠IgA肾病模型。用分子生物学和病理学方法对3组IgAN模型小鼠进行鉴定和比较。结果（1）葡聚糖组尿蛋白增高，伴有血尿；免疫荧光显示部分肾小球大量IgA沉积；光镜下肾小球系膜细胞增多，肝和脾可见弥漫性的粉染物质沉积；电镜下肾小球系膜区少量低电子密度的致密沉积物，肝和脾可见淀粉丝样物质沉积。（2）大肠杆菌外膜蛋白组尿蛋白增高，伴有血尿；免疫荧光显示肾小球有少量IgA沉积；光镜下肾小球系膜细胞轻度增多，间质炎细胞浸润明显；电镜下肾小球系膜区无电子致密沉积物。（3）金葡菌细胞膜20肽抗原决定簇组尿蛋白增高，伴有血尿；免疫荧光显示多数肾小球均可见大量IgA沉积；光镜下肾小球系膜细胞增多，伴系膜基质轻度增生；电镜下肾小球系膜区和基底膜的内皮细胞下可见高电子密度的致密沉积物。结论金葡菌细胞膜20肽抗原决定簇组诱导的IgAN模型从临床表现和病理学变化与人IgAN极其相似，是3种IgAN模型中最理想的IgAN模型。     

IgA肾病和非IgA系膜增殖性肾小球肾炎抗内皮细胞抗体的检测

对１２７例ＩｇＡ肾病（ＩｇＡＮ）患者和２５例非ＩｇＡ系膜增殖性肾炎血清进行了抗内皮细胞抗体ＡＥＣＡ的检测。结果表明：ＩｇＡ肾病患者和非ＩｇＡ系膜增殖性肾炎患者血清ＡＥＣＡ－ＩｇＧ较正常对照组高，而ＩｇＡＮ患者较非ＩｇＡ系膜增殖性肾炎患者ＡＥＣＡ－ＩｇＧ的水平高，Ｐ〈０．０５。ＩｇＡＮ患者的ＡＥＣＡ－ＩｇＡ水平较正常对照组高。ＩｇＡＮ患者按ＡＥＣＡ水平分为阳性与阴性组，对两组硬化面积比进行比较，未见     

IgA肾病小管间质病变TGF-β1检测的临床意义

目的观察IgA肾病（IgAN）小管间质病变患者转化生长因子-β1（TGF-β1）水平的相关性及临床意义。方法43例IgAN患者行肾活检，按小管间质损害程度积分大小分级，用ELISA法检测尿α1微球蛋白（a1-MG）、尿视黄醇蛋白（RBP）、尿B2微球蛋白（β2-MG）、血TGF-β1。结果IgA肾病的病理类型与其间质损害程度存在相关性，43例IgAN尿α1-MG、尿RBP、尿β2-MG、血TGF-β1均较正常对照组显著增高（P〈0．01），IgAN小管间质病变与尿α1-MG、尿RBP、尿β2-MG、血TGF—β1均显著正相关（P〈0．01）。结论血TGF-β1可作为诊断IgAN小管间质损伤又一可靠指标。     

End-Stage Renal Disease and Mortality Outcomes Across Different Glomerulonephropathies in a Large Diverse US Population

Objective

To compare renal function decline, incident end-stage renal disease (ESRD), and mortality among patients with 5 common glomerular diseases in a large diverse population.

HIV感染合并IgA肾病4例临床和病理分析

目的 研究HIV感染合并IgA肾病患者的临床和病理特点及治疗转归.方法 选择2002-2012年在北京协和医院住院的HIV感染合并肾脏损害,并经肾脏活检证实为IgA肾病的4例患者为研究对象,回顾分析这4例IgA肾病患者的临床、病理资料及治疗随诊情况.结果 4例患者均有不同程度蛋白尿和镜下血尿,血肌酐水平在正常范围,肾脏活检病理提示为不同程度的IgA肾病.4例患者均接受了高效联合抗反转录病毒治疗(HAART).3例患者的初始治疗使用了ACEI/ARB,其中2例效果不佳联合使用糖皮质激素治疗.1例肾脏病变好转后再次出现大量蛋白尿,考虑与抗病毒药物替诺夫韦有关,调整抗病毒治疗后再次缓解.治疗过程中所有患者的HIV病毒复制并未增加.结论 HIV感染合并肾脏病变除了经典塌陷型FSGS之外还可以合并IgA肾病,肾脏活检有利于明确诊断并指导治疗.     

Efficacy of immunosuppressive therapy in IgA nephropathy presenting with isolated hematuria

The role of immunosuppressive therapy in the management of IgA nephropathy (IgAN) remains controversial. No consensushas yet emerged on the specific treatment of IgAN and this ismostly related to the lack of complete understanding of themultifactorial pathogenesis of the disease. Choice of appropriatetherapeutic agents is further limited by the difficulty inidentifying patients who would most likely benefit from therapy.Immunosuppressive therapy has not been recommended in patientswith isolated hematuria and well preserved renal function becauseof their generally favourable prognosis and there are no clinicaltrials in this area. Considering that mild IgAN may be an earlystage of the disease and can be reversed by immunosuppressiveagents we have used prednisolone and azathioprine in patientswith isolated hematuria in a prospective, randomized, controlledstudy since 1988. In this prospective study we have evaluated theeffect of prednisolone with azathioprine on the clinical courseof IgAN and its impact on histologic parameters and preventionof progression in patients with isolated hematuria. We studied 43biopsy-proven IgAN patients (29 males and 14 females, agedbetween 13–63 years, mean age 28 ± 6) with isolated hematuria andwell-preserved renal function (C_cr 89.2 ± 10.2 ml/min). Thepatients were assigned to two groups: 21 patients receivedprednisolone (40 mg/day) and azathioprine (100 mg/day) orally forfour months (group A) and 22 patients received no specifictreatment for IgAN and served as a control group (group B). InGroup A prednisolone was reduced to 20 mg/day at the end of thesecond month, then slowly tapered over a two-month period andstopped. The median duration of follow-up was 60 months (range12–120 months). At the end of the therapy hematuria disappearedin 17 patients. In three patients who did not respond to therapy,microscopic hematuria persisted. Of the 22 patients of group B,three had episodes of gross hematuria and proteinuria >500mg/day. No significant changes in biochemical profile wereobserved in either group. Thirteen patients (eight from thetreated, five from the untreated group) underwent a repeat biopsyafter 12 ± 6 months (range 10–25). An improvement ofhistopathological features was noted in Group A, whiledeterioration was noted in Group B. We conclude that earlytreatment with prednisolone and azathioprine appears to bebeneficial in preventing the progression of immunologic renalinjury and in improving histopathological features in IgANpatients with isolated hematuria.     

TGF-β_1在IgA肾病中的作用

转化生长因子β1(TGF-β1)被认为是最重要的促纤维化因子之一。在IgA肾病中,一方面它能增加细胞外基质的合成并抑制其降解,从而导致肾小球硬化;另一方面它可调节肾小管上皮细胞向间充质细胞转化,从而导致肾间质纤维化。血管紧张素转化酶抑制剂和血管紧张素受体抑制剂不能完全阻断TGF-β1的表达。修饰素cDNA注入骨骼肌内可阻止纤维化进程,有可能成为治疗肾脏纤维化疾病的有效药物。     

Characteristics of patients with coexisting IgA nephropathy and membranous nephropathy

Background: Coexistence of IgA nephropathy (IgAN) and membranous nephropathy (MN) in the same patient is rare. Few studies have reported the clinical and pathological features of patients with combined IgAN and MN (IgAN–MN).

Methods: The clinico-pathological features, levels of galactose-deficient IgA1 (Gd-IgA1) and autoantibodies against M-type transmembrane phospholipase A₂ receptor (anti-PLA₂R) in sera were compared among IgAN–MN, IgAN, and MN patients.

Results: Twenty-six patients with biopsy-proven IgAN–MN were enrolled. The mean age at biopsy was 43.6?±?15.9?years, and 65.4% were male. Proteinuria and estimated glomerular filtration rate (eGFR) levels in patients with IgAN–MN were similar to that of MN patients. Compared with the IgAN patients, IgAN–MN patients showed a higher median proteinuria level (4.3 vs. 1.2?g/day, p?2, p?IgAN–MN patients presented with milder pathological lesions than IgAN patients according to the Oxford Classification. IgAN–MN patients had comparable serum levels of Gd-IgA1 with those of IgAN patients (353.4?±?95.5 vs. 347.0?±?109.6?U/mL, p?=?.801). Percentage of IgAN–MN patients with detectable serum levels of anti-PLA₂R was lower than that of MN patients (38.5% vs. 68.6%, p?=?.011).

Conclusions: IgAN–MN patients display similar clinical features to MN patients and milder pathological lesions than IgAN patients. IgAN–MN patients have similar levels of Gd-IgA1 to those of IgAN patients, and a lower proportion of anti-PLA₂R than MN patients.     

白细胞介素13在系膜增生性肾小球肾炎患者血浆及肾组织的表达

目的 探讨系膜增生性肾小球肾炎(MsPGN)患者血浆及肾组织白细胞介素13(IL—13)的表达，进一步了解MsPGN的分子病理机制，为临床治疗探索新的途径。方法 应用酶联免疫吸附试验(ELISA)和免疫组化ABC技术检测30例MsPGN患者血浆IL—13水平及其在肾组织的表达、定位和分布。结果 MsPGN患者血浆IL—13水平较正常对照组明显增高，以IgAN增高明显MsPGN患者肾小球及肾小管间质区IL—13表达较正常对照组增高，而以肾小管间质区表达更强，non-Iga MsPGN与IgAN相比，肾小管间质区IL—13表达无明显差异。结论 IL—13可能参与了MsPGN分子病理机制。