发病时的蛋白尿和足突融合在IgA肾病预后判断上的价值

目的：探讨发病时的蛋白尿〉1．0g／d和广泛足突融合在IgA肾病预后判断上的价值。方法：以1998年1月～2005年1月间肾活检诊断为IEA肾病-局灶硬化性肾小球肾炎（IgAN-FSGN）99例为研究对象，分析广泛足突融合和蛋白尿〉1．0g／d与肾小球硬化及小管间质病变的相关性。结果：电镜下显示肾小球脏层上皮细胞足突广泛融合24例（24．2％），足细胞无明显改变（包括足突细胞部分融合）75例（75．8％）。广泛足突融合组的重度肾小球硬化发生率为54．2％（13／24例）明显高于足细胞无明显改变组的28．0％（21／75例）；临床表现尿蛋白〉1．0g／d组44例（44．4％），尿蛋白〈0．5g／d组23例（23．2%）。尿蛋白〉1．0g／d组足突广泛融合的发生率为29．5％（13／44例）明显高于尿蛋白〈0．5g／d组的4．3％（1／23例），尿蛋白〉1．0g／d组的重度肾小球硬化发生率为40．9％（18／44例）明显高于尿蛋白〈0．5g／d组的13．0％（3／23例）。结论：广泛足突融合或蛋白尿〉1．0g／d均与IgAN-FSGN肾小球硬化的加重呈正相关，广泛足突融合可作为IgAN-FSGN病变进展的一个病理学标志，尿蛋白〉1．0g／d可作为反映IgAN—FSGN病变进展的一个临床标志。     

IgA肾病患者血清IgA1与系膜细胞共培养上清诱导足细胞凋亡

目的 探讨IgA肾病(IgAN)患者血清IgA1与系膜细胞共培养上清对足细胞凋亡的影响。 方法 用Jacalin 亲和层析柱和Sephacryl S-200 分子筛纯化蛋白。单体IgA1（mIgA1）热聚合为聚合体IgA1（aIgA1）。实验分为患者上清组、健康上清组和对照组，系膜细胞分别与IgAN患者的aIgA1、健康对照的aIgA1和5%胎牛血清共培养，收集上清，与同步化的足细胞作用。流式细胞仪检测细胞凋亡情况。实时定量PCR 检测凋亡相关基因Bcl-2、Bax、Fas和Fas-L表达情况。 结果 患者上清可诱导足细胞凋亡，其凋亡率显著高于健康上清组和对照组[（28.5±5.9）%比（22.5±5.8）%、（20.5±4.5）%， 均P < 0.05]。患者上清可诱导足细胞Fas mRNA 升高，为对照组的1.89倍（P < 0.05）， 而Bcl-2 mRNA下调为对照组的72%（P < 0.05）。患者上清组的AngⅡ和TGF-β1水平均高于健康上清组[（13.2±3.4） ng/L比（8.2±2.3） ng/L，P < 0.05；（15.4±3.4） ng/L比（10.8±3.2） ng/L，P < 0.05]。 结论 IgAN患者血清IgA1与系膜细胞共培养上清可诱导足细胞凋亡，可能参与IgAN的进展。     

伴足细胞尿的IgA肾病的临床病理特征

目的 探讨伴足细胞尿的IgA肾病（IgAN）患者的临床病理特点。方法 入选IgAN患者36例,其中男性20例,女性16例,平均年龄（34．1±12．2）岁。10例健康志愿者为健康对照。足细胞排泄的定量检测采用尿沉渣涂片免疫组化染色直接计数。进行尿液足细胞排泄与肾脏病理的相关分析。结果 （1）IgAN患者尿细胞podocalyxin阳性率为61%,健康对照组为0（P＜0．05）。（2）与非大量蛋白尿（＜3．0 g/24 h）IgAN患者比较,大量蛋白尿（≥3．0 g/24 h）IgAN患者的尿液足细胞检测阳性率、尿液足细胞排泄数、足细胞与尿肌酐的比值以及足细胞占尿液小管上皮细胞的百分数均显著增高（P＜0．05）。IgAN患者足细胞排泄水平与蛋白尿水平呈正相关（r=0．446,P=0．007）。（3）与无足细胞尿的患者比较,伴足细胞尿的IgAN患者的蛋白尿水平显著增高,血浆白蛋白水平显著降低,肾小管上皮细胞与尿肌酐的比值亦显著增高（P＜0．05）。但伴与不伴足细胞尿的2组IgAN患者在年龄、性别、血压、Scr、血红蛋白水平以及血浆脂质代谢等方面差异均无统计学意义（P＞0．05）。（4）尿足细胞的排泄与细胞新月体或细胞纤维性新月体、小球血管襻腔狭窄和足突广泛融合病变有关,而与系膜、内皮细胞病变及局灶基底膜增厚无关。伴足细胞尿的患者肾小球和肾小管间质纤维化更明显（P＜0．05）。伴有新月体的患者其尿液足细胞排泄水平、尿液上皮细胞和管型的排泄均增加（P＜0．05）。结论 足细胞尿不仅是IgAN患者肾小球损伤的结果,也是IgAN患者活动性损伤的指标。足细胞尿排泄的水平与蛋门尿水平呈正相关,与肾脏病理类型也有一定的关系。     

IgA肾病患者尿足细胞数及肾组织podocalyxin表达与临床病理的相关分析

目的 探讨尿足细胞数和肾组织中足细胞顶膜区的特异性标记蛋白podocalyxin（PCX）的表达与IgA肾病(IgAN)患者临床和病理改变的关系。 方法 收集50例IgAN患者活检前3 d的每天晨尿和20例体检健康对照者的晨尿各100 ml,离心去上清于TXD3细胞离心涂片机上制成涂片。用抗人PCX单克隆抗体分别对尿沉渣涂片和肾组织切片进行免疫组化染色,于光学显微镜下计数尿足细胞排泄数,以及用计算机图像分析系统测量和计算肾小球PCX平均吸光度值。IgAN按Lee分级分成5组,并用Katafuchi半定量积分法记分。比较各组尿足细胞数和肾组织PCX平均吸光度值,并与各项病理指标评分和临床生化指标进行相关性分析。 结果 IgAN组尿中足细胞数显著高于健康对照组（P < 0.01）。IgAN Lee分级各组组间尿足细胞中位数两两比较,Ⅰ-Ⅱ级组低于Ⅲ、Ⅳ、Ⅴ级组（P < 0.05）;Ⅲ级组显著低于Ⅴ级组（P < 0.05）;Ⅲ级组低于Ⅳ级组和Ⅳ级组低于Ⅴ级组,但差异无统计学意义。尿足细胞阳性率在Ⅳ、Ⅴ级组最高（100%）,在LeeⅠ-Ⅱ级组最低（55%）。IgAN患者随着Lee分级升高,肾小球足细胞PCX表达下调,两两比较结果显示,Ⅰ-Ⅱ级组显著高于Ⅲ、Ⅳ、Ⅴ级组（P < 0.05）;Ⅲ、Ⅳ级组显著高于Ⅴ级组（P < 0.05）;Ⅲ级组稍高于Ⅳ级组（P > 0.05）。IgAN患者尿足细胞排泄数与肾小球PCX表达量呈负相关（r = -0.702,P < 0.01);与24 h尿蛋白量呈正相关（r = 0.465,P < 0.01）;与肾小球和肾小管病理积分均呈正相关（r = 0.233,r = 0.307,均P < 0.05）。肾小球PCX表达量分别与肾小球和肾小管病理积分呈负相关（r = -0.560,r = -0.377,均P < 0.05）;与24 h尿蛋白量呈负相关（r = -0.367,P < 0.05）。 结论 IgAN患者尿足细胞排泄量可反映肾组织足细胞缺失程度,肾小球足细胞损伤脱落可能参与IgAN的发生发展,其尿足细胞数有可能作为反映疾病进展的重要指标。     

足细胞损伤与IgA肾病

近年来,许多不同的病因基本是通过足细胞的损伤而启动IgA肾病的进程,尤其对足细胞多种蛋白分子的研究可进一步了解IgA肾病的发病机制.     

IgA肾病中足细胞损伤机制的研究进展

IgA肾病（IgAN）是一种常见的原发性肾小球疾病,在我国占原发性肾炎患者的25%～33%,是引起终末期肾衰竭最常见的原因之一[1]。IgAN在诊断后5～25年内,约有15%～40%患者进入终末期肾衰竭而不得不接受肾脏替代治疗[2]。近年来足细胞在IgAN中的损伤成为研究热点,现将足细胞的损伤机制阐述如下。     

足细胞损伤与IgA肾病

近年来,许多不同的病因基本是通过足细胞的损伤而启动IgA肾病的进程,尤其对足细胞多种蛋白分子的研究可进一步了解IgA肾病的发病机制.     

足细胞损伤与IgA肾病

近年来,许多不同的病因基本是通过足细胞的损伤而启动IgA肾病的进程,尤其对足细胞多种蛋白分子的研究可进一步了解IgA肾病的发病机制。     

尿足细胞阳性IgA肾病患者不同蛋白尿水平临床病理分析

目的：探讨尿足细胞阳性的IgA肾病患者不同蛋白尿水平的临床病理特点.方法：选取原发性IgA肾病尿足细胞阳性患者41例,收集患者临床病理资料,根据尿蛋白水平分成3组：组1（≤0.5 g/24 h）（n=9）,组2（〉0.5 g/24 h,〈1.0 g/24 h）（n=14）,组3（≥1.0 g/24 h）（n=18）,比较3组临床病理特点.结果：（1）临床特点：组1患者收缩压、eGFR、UA均较组3差异有统计学意义（P〈0.05）,且这些指标在三组间随蛋白尿水平呈现递进表现.组2和组3仅在收缩压、UA方面差异有统计学意义（P〈0.05）;（2）病理特点：组1在节段性肾小球病变比例及间质炎细胞浸润方面较组3轻,差异有统计学意义（P〈0.05）;组1在节段性肾小球病变比例及节段损伤积分方面较组2轻,差异有统计学意义（P〈0.05）;组2和组3两组病理改变差异无统计学意义（P〉0.05）.结论：尿足细胞阳性的IgA肾病患者中,尿蛋白水平仍然是肾脏病轻重的一个指标,与临床病理关系密切.     

肾炎康复片治疗对IgA肾病患者尿足细胞nephrin的影响

近年来,随着对肾小球足细胞研究的不断深入,人们逐渐认识到肾小球足细胞受损不仅可导致蛋白尿的发生,还是肾小球硬化的始动环节,各种损伤如血流动力学改变、足细胞基因突变（包括nephrin、a—actin4、CD2AP等）等均可直接引起足细胞脱落,进而导致肾小球基底膜裸露、肾小球硬化等一系列改变。IgA肾病是我国常见的慢性肾小球疾病之一,其预后不良,最终可导致慢性肾衰竭。我们采用肾炎康复片治疗IgA。肾病,观察其对患者尿足细胞的影响。     

少量蛋白尿和（或）血尿IgA肾病临床病理分析

目的 了解表现为少量蛋白尿和（或）血尿IgA肾病（IgAN）患者的肾脏病理特征及其与临床表现的关系。 方法 对1993年1月至2009年10月肾活检确诊为IgAN,且表现为少量蛋白尿 （<1 g/24 h）和（或）血尿,Scr<133 μmol/L的患者的临床和病理资料进行回顾性分析。病理学分级参照Lee分级及Katafuchi半定量积分标准。应用多因素logistic回归法分析肾脏病理损伤的危险因素。 结果 符合入选标准共316例,男123例,女193例,肾穿时年龄（33.10±10.69）岁。蛋白尿伴血尿占84.5%、单纯血尿占7.6%、单纯蛋白尿占7.9%。16.5%患者伴有高血压。CKD1、2、3期分别占76.9%、20.9%和2.2%。Lee Ⅲ级及以上患者占31.3%。52.8%患者有不同程度肾小球硬化;20.3%伴新月体形成;22.5%伴小管萎缩;16.8%有间质纤维化;24.7%有血管病变。肾小球硬化积分与估算肾小球滤过率（eGFR）呈负相关;与蛋白尿及平均动脉压（MAP）呈正相关。肾小管间质病变积分与eGFR及血红蛋白(Hb)呈负相关;与尿蛋白量呈正相关。血管病变积分与MAP呈正相关;与eGFR呈负相关(均P < 0.05)。多因素logistic回归分析结果显示,肾活检时尿蛋白量（OR = 8.564,P < 0.01）、Scr（OR = 1.031,P< 0.01）及Hb（OR = 0.975,P < 0.01）是肾脏病理损伤（LeeⅢ级以上）的独立危险因素。 结论 部分表现为少量蛋白尿和（或）血尿IgAN患者的病理改变并不轻,且肾功能已减退。尿蛋白量、Scr、Hb是预测肾脏病理损伤程度的独立危险因素。肾活检对这些患者明确诊断、判断病情和预后、制定个体化治疗方案十分重要。     

IgA肾病呈单纯血尿和(或)轻度蛋白尿临床病理分析

目的 探讨单纯血尿和／或轻度蛋白尿IgA肾病患者病理特点及临床病理相关性,并进行危险因素分析。方法 选取肾脏疾病数据库1988-2001年我科收住的248例临床表现为单纯血尿和／或伴有轻度蛋白尿(尿蛋白定量≤1.0 g／d)的IgA肾病患者,血压、肾功能均正常,采用单盲法进行临床和病理分级(Haas分级),多因素回归分析法进行病理损伤的危险因素评估。结果(1)临床特点:49％(121例)患者同时存在血尿和蛋白尿,47％(117例)为单纯血尿,4％(10例)为单纯蛋白尿;(2)病理特点:35.5％(88例)病理损伤偏重,Haas分级Ⅱ-Ⅳ级。蛋白尿是病理损伤偏重(HaasⅡ级以上)的独立危险因素(OR=3.46,95％CI:1.54-7.79,P=0.002)。随着蛋白尿程度的增加,其病理损伤偏重的危险性亦明显增加。结论 相当一部分临床表现轻微的IgA肾病患者病理偏重,蛋白尿是危险因子,即使轻度蛋白尿亦和病理损伤明显相关。对于怀疑IgA肾病患者,尽管只有少量蛋白尿亦应进行肾活检,有助于发现病理损伤偏重的患者。     

Efficiency of glucocorticoid treatment in IgA nephropathy with massive proteinuria

Objective To investigate the clinicopathological characteristics of IgAN patients with massive proteinuria, as well as their treatment response to glucocorticoids and long-term prognosis. Methods Clinical and pathological parameters were collected in patients diagnosed with IgA nephropathy in our hospital from Jan 2003 to Oct 2015. Patients were followed up for at least six months under the treatment with full dosage of glucocorticoids. Responses of patients with and without nephrotic syndrome were compared. Results A total of 156 patients were enrolled for the analysis (86 patients in the nephropathic proteinuria group, and 70 patients in the nephrotic syndrome group). Patients presented with nephrotic syndrome showed higher proportion of IgM deposition in renal slides. There exited no difference in treatment response to glucocorticoids between the two groups. Patients with full or partial remission showed a better prognosis by Kaplan-Meier analysis than no remission group (P＜0.001). The ratio of segmental sclerosis was negatively correlated with treatment response to glucocorticoids by multiple linear regression (β value=-0.330, P＜0.001). Multivariate Cox regression model showed that glomerular density (HR=0.45, P=0.02) and eGFR (HR=0.95, P=0.001) were independent influential factors for renal survival. Conclusions Patients presented with nephrotic syndrome show higher proportion of IgM deposition in renal slides. Patients in remission after treatment with 6-month glucocorticoids present a better prognosis than no remission patients, and glomerular density as well as eGFR are independent influential factors for renal survival.     

Determination of plasma antiglycan autoantibodies in patients with IgA nephropathy and the correlation with clinical characteristics

Objective To establish the measurement of IgA1 O-glycan-specific antiglycan autoantibodies in patients with IgA nephropathy (IgAN), and evaluate their role in the development and progression of IgAN. Methods In the IgAN regular follow-up cohort of Peking University Institute of Nephrology from January 2006 to December 2015, 170 patients drawn by stratified randomization were enrolled in this study. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of plasma galactose-deficient IgA1 (Gd-IgA1) and antiglycan autoantibody (IgG and IgA1). The correlation between antiglycan autoantibodies and clinicopathological parameters was analyzed by linear correlation and multiple linear regression analysis. The receiver operating characteristic curve (ROC) was used to evaluate the value of plasma anti glycide antibodies in the diagnosis of IgAN. Results IgG and IgA1 antiglycan autoantibodies that specifically recognized Fab-hinge region (Fab-HR) antigens could be detected in both IgAN and healthy control group. Agglutinin inhibition test showed that the specific antigen epitope was N-acetylgalactosamine (GalNAc) residue exposed to galactose deficiency in IgA1 hinged region. There was no significant difference in the absolute levels of plasma IgG antiglycan autoantibodies between IgAN and healthy controls (P=0.963). After adjustment of the plasma level of IgG, the normalized antiglycan autoantibody (ln[IgG antiglycan antibody/IgG]) in patients with IgAN was significantly higher than that in healthy controls (0.58±0.31 vs 0.37±0.11, P﹤0.01). The normalized level of IgG antiglycan autoantibody in IgAN patients was positively correlated with 24 h urine protein level during renal biopsy (Spearman r=0.183, P﹤0.05), and was also significantly correlated with 24 h urinary protein level after adjusting for baseline clinical and pathological factors (β=0.713, 95%CI 0.323-1.102, P﹤0.01). The area under ROC curve (AUC) of normalized IgG antiglycan autoantibody in the diagnosis of IgAN was 0.764 (95% CI 0.682-0.845, P﹤0.05). Using the cut-off value of 0.396, the sensitivity and specificity of normalized IgG antiglycan autoantibody for IgAN were 0.729 and 0.700 respectively. There was no significant difference in the absolute or normalized levels of IgA1 antiglycan autoantibodies between IgAN patients and healthy controls. Conclusions Gd-IgA1-specific antiglycan autoantibodies can be detected both in IgAN patients and healthy controls. They are elevated in some patients with IgAN and possibly involved in the development of IgAN.     

IgA肾病患者血压节律及其与临床病理指标的关系

目的 探讨IgA肾病患者血压昼夜节律与临床病理指标的关系.方法 采用横断面调查研究.选择2009年3月至8月在IgA肾病数据库登记的原发性IgA肾病患者,收集临床病理资料,并通过动态血压监测IgA肾病患者血压昼夜节律情况.用(日间血压平均值-夜间血压平均值)/日间血压平均值判断血压昼夜节律状况.比较血压节律正常组及异常组的临床病理指标.结果 共93例患者完成动态血压监测并纳入分析.其中68例(73％)血压节律消失,在慢性肾脏病(CKD)1期、2期及3期以上组血压节律消失的比例分别70％、70％及81％,3组间差异无统计学意义(P=0.587).非勺型血压在血压正常组与高血压组比例分别为69％和77％(P=0.373).血压节律消失与年龄、性别、血压、蛋白尿、肾功能以及肾脏病理损伤程度无相关.在随访时间超过12个月的54例中,非勺型血压组eGFR下降速率虽快于勺型血压组,但差异无统计学意义(P=0.329);在其中29例并发高血压患者中,非勺型血压组eGFR下降速率快于勺型血压组,且差异有统计学意义[(-6.79±11.58)比(-0.34±1.74)ml·min-1·(1.73 m2)-1·年-1,P=0.019].结论 IgA肾病早期即可出现明显的血压节律消失.IgA肾病伴高血压患者的血压节律消失可能是影响肾功能进展的危险因素.     

少量蛋白尿IgA肾病临床研究现状

少量蛋白尿IgA肾病(24 h尿蛋白<1 g)的患者既往认为长期预后良好,且肾活检比例低,普遍未予积极有效的治疗。近年来陆续有研究表明,少量蛋白尿IgA肾病患者长期预后并不乐观,因此需提高对少量蛋白尿IgA肾病临床、病理、治疗及预后的认识及理解。本文将对少量蛋白尿IgA肾病临床表现、肾脏病理、治疗及预后4个方面予以综述。     

Study on glomerular microvascular injury and repair in patients with IgA nephropathy and its relationship with intermedin

Objective To investigate the glomerular microvascular injury and repair in patients with IgA nephropathy (IgAN) as well as its relationship with intermedin (IMD). Methods Eighty cases of renal tissue taken from patients first diagnosed as IgAN in Shanxi Provincial People's Hospital Affiliated to Shanxi Medical University and 15 cases of normal renal tissue were detected by the expression of glomerular IMD, CD31, and VE-cadherin through immunohistochemical method. ELISA method was used to detect VEGF and IMD of plasm from 31 normal subjects and 36 cases chosen from the IgAN patients. Their changes and internal relationship were analyzed according to Lee's and chronic kidney disease (CKD) classification. Results (1) Compared with the control group the expressions of CD31, IMD, and VE-cadherin in IgAN patients were statistically significant (P＜0.01). Compared with the control group the levels of IMD and VEGF in plasma of IgAN patients in early stage of CKD group and late stage of CKD group were statistically significant (P＜0.01). (2) Correlation analysis: the expression of glomerular CD31 and Lee's classification were negatively correlated (r=-0.232, P＜0.05); glomerular IMD was negatively correlated with Lee's classification (r=-0.241, P＜0.05), while positively correlated with glomerular VE-cadherin (r=0.417, P＜0.01). VEGF in plasma of IgAN patients was positive correlated with CKD classification, BUN (r=0.458, 0.409, P＜0.05), and negatively correlated with serum ALB (r=-0.532, P＜0.01). Conclusion Microvascular injury exists in patients with IgAN. The expression of VE-cadherin and IMD are positively correlated, suggesting that IMD may be involved in the progression of vascular protection and angiogenesis in IgAN. The contents of IMD and VEGF in plasma of IgAN patients increase, indicating that they may play a role in the progression of IgAN.