成人肾小球疾病145例临床病理分析

目的了解成人肾小球疾病的病理类型及其特点。方法分析我院145例成人肾小球疾病患者的年龄性别分布、肾病理类型及其与临床表现的关系。结果145例患者中，原发性肾小球疾病占72．4％，男／女为1／1．1；继发性肾小球疾病占22．8％，男／女为1／1．54；遗传性肾小球疾病占4．8％，男／女为2．5／1。原发性肾小球疾病病理类型以IgA肾病(IgAN)为主，占43．9％，膜性肾病(MN)占17．1％，微小病变(MCD)占17．1％，系膜增生性肾小球肾炎(MsPGN)占15．2％，毛细血管内增生性肾小球肾炎(EnPGN)占3．8％，膜增生性肾小球肾炎(MPGN)占1．0％，局灶节段性肾小球硬化(FSGS)占1．0％。继发性肾小球肾炎中以狼疮性肾炎(LN)为主，占27．3％，乙型肝炎相关性肾炎占21．2％，过敏性紫癜肾炎占18．2％，系统性血管炎占18．2％，肾淀粉样变占6．0％，流行性出血热占3．0％，多发性骨髓瘤占3．0％，糖尿病肾病(DN)占3．0％。临床表现蛋白尿和(或)血尿占34．0％，肾病综合征占47．3％，急性肾衰竭占10．7％，急性肾炎综合征占8．0％。结论原发性肾小球疾病是成人最常见的肾小球疾病，以IgAN为主。高发年龄虽在青壮年，但不应忽视老年发病。继发性肾小球疾病中以LN多见，女性多发，其它继发性肾小球疾病逐渐增多。     

乙型肝炎病毒相关性肾炎的发病机理及治疗探讨

近30年来,乙型肝炎病毒(HBV)感染在肾小球肾炎发病机制中的地位受到人们普遍关注。目前国内外学者认为,HBV感染与多种病理类型的肾小球肾炎相关,除原发性肾小球肾炎中的膜性肾病(MGN),膜增生性肾炎(MPGN),系膜增生性肾炎(MsPGN)外,IgA肾病(IgAN),狼疮肾炎(LN)也被认为可能与HBV感染有关。     

IgA肾病牛津分型:优势及不足

IgA肾病(IgA nephropathy,IgAN)是一种免疫病理诊断,特征性病变是肾小球系膜区单纯IgA或以IgA为主的免疫球蛋白沉积。IgAN是全球最常见的肾小球肾炎病理类型,在亚洲人中占原发性肾小球肾炎(primary glomerular nephritis,PGN)的30%~58.2%,在高加索人中约占30%~40%,但非裔的患病率低,仅2%左右~[1]。中国是IgAN的高发地     

10594例肾活检病理资料分析

目的回顾性分析南京军区南京总医院1979年1月～2000年10月10 594例因肾脏疾病行经皮肾活检者的病理类型,并比较前后10年间病理类型的变化.方法参照WHO(1982年及改良的1995年)肾小球疾病组织学分型修订方案,结合临床资料、实验室检查结果、免疫病理及超微结构改变特点,提出诊断设想,然后与临床医师共同讨论明确诊断.结果本组10 002例肾脏疾病患者行肾活检时的平均年龄31.4±13.0(范围1～78)岁,男女之比1.301;592例移植肾活检患者活检时的平均年龄为37.5±9.1(范围16～66)岁,男女之比为2.361.除外移植肾活检者,本组原发性肾小球疾病占70.58%,继发性肾小球疾病占22.82%,遗传性和先天性肾脏疾病占1.01%,小管间质性疾病占3.18%,新发现和罕见的肾脏疾病占0.15%,终末期肾脏疾病占0.96%,未分类者占1.30%.原发性肾小球疾病以IgA居多(39.55%),其次分别为系膜增生性病变(29.78%),膜性肾病(9.54%),FSGS(5.82%)…….最常见的继发性肾脏病变是狼疮性肾炎(57.78%).近10年来,继发性肾小球疾病的检出率逐渐增高.分析前后10年间各种原发及继发性肾脏病的检出率,证实近10年来IgA肾病、膜性肾病明显增多(P均＜0.001),新月体性肾炎(P＜0.0001)及抗GBM肾炎、HUS/TTP均有增加(P均＜0.001),而毛细血管内增生性肾炎、IgM肾病则减少(P＜0.001,P＜0.01).本组临床表现为慢性肾衰者607例行肾活检,其病因包括IgA肾病26.7%,血管炎14.3%……,临床以急性肾衰起病者则以急性间质性肾炎(29.54%)和急性肾小管坏死(26.02%)为主,新月体性肾炎(11.92%)和血管炎(10.03%)也很常见.除常见的肾小球、小管-间质和遗传性疾病外,本组还发现罕见及新认识的疾病如Niemann Pick病、Fabry病、POEMS综合征及脂蛋白肾小球病等.分析移植肾活检患者的病理类型,证实移植后肾功能减退除排斥反应外,还包括急性肾小管坏死等多种病因.结论本资料为国内最大系列的肾活检病理类型分布的研究,阐明了中国肾小球、小管-间质等疾病谱及20年来疾病的变化,并与文献进行了对比.本资料证实,近10年来原发性肾小球肾炎仍为我国最常见的肾小球疾病,其中以IgAN最常见,继发性肾脏病以LN多见,除LN外的其它继发性肾脏病和少见病逐渐增多;以慢性肾功能不全起病最常见的病理类型是IgA肾病,血管炎次之,急性肾衰则以急性间质性肾炎,急性肾小管坏死及新月体性肾炎等常见;移植后肾功能不全的病因除排斥反应外还有多种原因.     

泌尿系统疾病

990501粘附分子P选择素在人类肾小球疾病中裹达及其愈义/周同…//中华肾脏病杂志一1998,1‘(3)一1马5一1 58 检测1:33例、其中轻微病变4例、IgA肾病1续例、非19八系膜增生性肾炎34例、膜性肾病4例、毛细胞管内增生性肾炎2例、肾小球局灶节段透明变性1。例、紫瘫性肾炎2例、狼疮性肾炎44例,以硬化为主的肾小球晚期病变19例。分组I组23例:’肾小球内无明中国医学文摘·内科学1999年第20卷第l期显炎细胞浸润;双组91例:肾小球有明显炎症性改变和细胞增生;班组19例:肾小球炎症过程趋向静止及〔或)出现较多肾小球硬化;正常肾组织10例。结果:正常…     

IgA肾病系膜区IgA沉积的机制

IgA肾病(IgAN)是最常见的原发性肾小球肾炎。在我国，IgAN占原发性肾炎的39．5％。IgAN患者预后悬殊，20％～40％患者20～25年后进展至终末期肾功能衰竭。IgAN的始发因素是系膜区IgA沉积，其中主要是多聚IgA1(pIgA1)沉积，伴或不伴IgG、C3沉积。IgA沉积于系膜区后将引起肾小球炎症和损伤，病变可完全吸收消散或遗留硬化性病变，也可出现肾小管萎缩、间质纤维化，导致进行性肾功能减退。其中，     

狼疮肾炎患者肾组织中结缔组织生长因子的转录表达及意义

目的探讨人类狼疮肾炎(LN)患者肾组织中结缔组织生长因子(CTGF)的基因转录和蛋白表达与肾纤维化之间的关系。方法应用免疫组织化学和原位杂交技术,以15例正常肾组织为对照,观察了36例LN患者肾组织中CTGF表达的分布和表达量的变化,分析肾组织中CTGF表达与LN肾间质病变的内在联系。结果LN患者肾组织的CTGF表达主要分布在肾小管上皮细胞和肾间质细胞、肾小球脏层和壁层上皮细胞和系膜区细胞。正常肾组织没有或只有极弱的CTGFmRNA转录和蛋白表达;LN患者肾组织CTGFmRNA转录及蛋白表达量较正常肾组织显著增高(CTGFmRNA:8.22±3.13比1.12±0.23;CTGF蛋白:8.74±3.24比1.21±0.22,P均<0.001);LN患者肾组织CTGF表达量与肾间质病变程度呈正相关(r=0.863,P<0.01);Ⅳ型LN患者肾组织CTGF表达量显著高于非Ⅳ型LN患者(CTGFmRNA:10.73±3.61比4.78±1.82CTGF蛋白:11.03±1.12比5.02±1.31,P均<0.01);CTGF的蛋白表达量与转化生长因子(TGF)-β1、纤维结合蛋白(Fn)及ColⅢ的表达量呈正相关(r=0.704、r=0.783及r=0.756,P均<0.01)。结论CTGFmRNA转录和蛋白表达量的增加与LN患者肾小管间质病变程度加重呈正相关。作为TGF-β的下游介质,CTGF可通过促进细胞外基质如FN和ColⅢ等合成,从而在LN患者肾小球硬化及肾小管间质纤维化的     

4298例成年人肾小球疾病病理类型及流行病学特点

了解我国成年人肾小球疾病病理类型及流行产现学特点。方法：分析解放军肾脏病研究所１９８０－１９９６年间经肾活检确诊的肾小球疾病４２９８例。结果：原发性肾小球肾炎占７６．８％，继发性肾小球肾炎２２．８％，遗传性肾病０．４％；原发性肾小球肾炎男：女＝１．８１：１，继发性肾小球肾炎男：女＝０．４６：１，两组间存在统计学差异；原发性肾小球肾炎各型所占比例依次是：ＩｇＡ肾病（ＩｇＡＮ）３６．９％、系膜增生性肾     

原发性IgA肾病危险因素及危险评分研究进展

原发性IgA肾病(IgAN)是一种免疫病理定义的疾病,最显著的病理特征是以IgA为主的免疫复合物沉积于肾小球系膜区。该病的病理异质性较大,光镜下可见到接近正常结构的轻微病变,也可见到伴有新月体形成的严重增生性肾小球病变,部分患者则以局灶节段硬化样病变为主~[1]。IgAN患者临床表现差异也较大,较轻微的患者仅表现为无症     

NF-κB在IgA肾病中的表达及意义

采用免疫组化法观察36例IgA肾病(IgAN)肾组织中核因子-kB(NF-kB)的表达.结果 :在正常肾组织及IgAN Ⅰ级病变组肾组织中NF-kB的表达较弱.在IgAN Ⅱ～Ⅲ级组、Ⅳ～Ⅴ级组肾小球及肾小管间质中NF-kB表达均较对照组增强,随着肾组织病变加重其表达增强;Pearson相关分析表明NF-kB的表达与24 h尿蛋白定量和内生肌酐清除率紧密相关.认为NF-kB参与IgAN的进展,NF-kB的表达与IgAN进行性损伤有关.     

Interferon-inducible Mx1 protein is highly expressed in renal tissues from treatment-naïve lupus nephritis,but not in those under immunosuppressive treatment

Objectives: The aim of this study was to clarify the consequences of Mx1, one of the IFN-inducible proteins, in the peripheral blood as well as in renal tissues in patients with systemic lupus erythematosus (SLE).

Patients and methods: Mx1 protein concentrations in (PBMCs) from 18 SLE patients mostly in their stable disease status, 11 IgA nephropathy (IgAN) patients, 5 ANCA-associated vasculitis (AAV) patients and 16 healthy controls were measured using enzyme-linked immunosorbent assay (ELISA). Mx1 expression in renal specimens from 18 patients with lupus nephritis (LN), 18 with IgAN and 10 with AAV were evaluated using immunohistochemistry.

Results: Mx1 protein concentrations in lysates of PBMCs were significantly higher in SLE patients compared with those in other three groups. Mx1-positive area in renal tissues was significantly dominant in both glomeruli and renal tubules of LN compared with other renal diseases. Renal Mx1 protein levels were lower in LN after immunosuppressive treatment, compared with those from immunosuppressant-naïve patients.

Conclusion: Mx1 levels were upregulated in lupus peripheral blood even when their disease activities were stable. On the other hand, Mx1 was highly expressed in kidneys from patients with LN before treatment, which was decreased after immunosuppressive treatment. These results suggest that Mx1 is a potential marker for the diagnosis of SLE in the peripheral blood and also for the activity of lupus nephritis in the kidney.     

Increased expression of selectins in kidneys of patients with diabetic nephropathy

Summary In diabetic nephropathy leukocytes, mainly composed of monocytes/macrophages, which accumulate in the glomeruli and the interstitium, play an important part in the progression of glomerulosclerosis. The infiltration of leukocytes into inflammatory tissues or atherosclerotic lesions is mediated by adhesion molecules, which are expressed on the vascular endothelial cells, although little is known about the mechanism of leukocyte infiltration into diabetic renal tissues. P- and E-selectin are leukocyte adhesion molecules, which are expressed on the vascular endothelial cells and promote the adhesion of leukocytes to the endothelium. We investigated the expression of P- and E-selectin in the kidney tissue of patients with diabetic nephropathy and compared it with that of patients with other glomerular diseases (minimal change nephrotic syndrome, membranous nephropathy, IgA nephropathy, mesangioproliferative glomerulonephritis, and lupus nephritis). Expression of P- and E-selectin were both significantly increased in the glomeruli and the interstitium of patients with diabetic nephropathy as compared with those with other glomerular diseases. P- and E-selectin were both expressed along the glomerular capillaries and the peritubular capillaries in the interstitium. Neither P- nor E-selectin were correlated with the number of infiltrated leukocytes in the glomeruli, however, interestingly the E-selectin expression on peritubular capillaries was correlated with the number of infiltrated CD14 positive cells in the interstitium. These results suggest that E-selectin may play a key role in leukocyte infiltration into the renal interstitium in patients with diabetic nephropathy. [Diabetologia (1998) 41: 185–192] Received: 22 April 1997 and in final revised form: 29 September 1997     

血管紧张素转换酶抑制剂对IgA肾病的疗效及影响因素分析

目的 观察血管紧张素转换酶抑制剂（ACEI）对IgA肾病（IgAN）的疗效及其影响因素。方法 131例IgAN患者随机分为治疗组和对照组,治疗组应用ACEI（苯那普利10mg/d)治疗;对照组为非ACEI治疗组;对肾脏病理改变进行Lee氏分级并对各种病变进行半定量分析。结果 治疗组的显效率和总有效率均明显高于对照组（P均＜0.05),治疗1个月后治疗组尿蛋白即有显著下降,3个月时较1个月时仍有明显下降（P＜0.05),6、18个月与3个月时相比差异无显著性;血肌酐和肌酐清除率治疗前后比较无明显变化;对照组尿蛋白1个月时有升高趋势,3个月后较治疗前升高且有显著性（P均＜0.05）;肌酐清除率1个月时略有下降,3个月后与治疗前比较有显著下降（P均＜0.01)。单因素分析显示高血压、肾功能不全、Lee氏Ⅴ级、间质病变Ⅳ级、重度血管病变及肾小球硬化超过75％的患者,应用ACEI的疗效不如无高血压、肾功能正常、Lee氏Ⅰ-Ⅱ级、间质病变Ⅰ级、轻度血管病变和肾小球硬化小于25％的患者。多因素分析显示疗效与系膜增生程度呈正相关,与病程、肾小球硬化率及肾小动脉病变程度呈负相关。结论 应用ACEI治疗IgAN有明显降低蛋白尿和保护肾功能作用,影响疗效的主要因素为系膜增生程度、肾小球硬化率、肾小动脉病变程度及病程。     

Expressions of IL-18 and its binding protein in peripheral blood leukocytes and kidney tissues of lupus nephritis patients

To investigate the expressions of IL-18 and its binding protein (IL-18BP) in peripheral blood leukocytes and kidney tissues in patients with lupus nephritis (LN). SYBR-green-dye-I-based real-time quantitative PCR method was used to compare the gene expression levels (indicated as 2^?ΔΔCT value) of IL-18 and IL-18BP in the peripheral blood leucocytes of LN patients and those in normal controls. Serum levels of IL-18 were measured with ELISA method. Immunohistochemical evaluation of IL-18 and Il-18BP expression in LN was carried out on frozen renal biopsy sections. IL-18BP mRNA expression levels in LN patients were significantly lower than those of normal controls (P?<?0.01). Serum levels of IL-18 in LN patients were significantly higher than those of normal controls (P?<?0.01). It is noticeable that serum IL-18 levels in the patients treated with glucocorticoids and cyclophosphamide was lower than those treated with glucocorticoids only or glucocorticoids and other immune inhibitors such as chloroquine/hydroxychloroquine and azathioprine. Expression of IL-18 in renal glomeruli was higher in type-IV and type-V LN patients than in type-III LN patients. LN patients present lower IL-18BP mRNA expression and higher serum levels of IL-18 than those in normal controls. The preponderance of IL-18 in glomeruli from LN patients indicates IL-18 may be concerned with the local inflammation. Up-regulation of IL-18BP expression and control of the biological activity of IL-18 may be a therapeutic approach to LN patients.     

肾病综合征合并特发性急性肾功能衰竭10例分析

１０例肾病综合征患者在病程中合并无明显诱因的急性肾功能衰竭，其临床特征均为大量蛋白尿，高度水肿，病程中突发少尿，尿渗透压降低，肾功能急骤性恶化，血肌酐及尿素氮升，高肾脏病理组织学显示肾小球无明显病变或轻微病变，但多数病人肾间质高度水肿及部分病人有肾小管上皮细胞呈灶状脱落坏死，经利尿、肾上腺皮质激素等治疗肾功能逐步恢复正常，提示肾病综合征合并特发性急性肾功能衰竭并不少见，发生率为肾功能逐步恢复正常。     

Renal biopsy in elderly adults over 75 years of age

The results of 177 renal biopsies (RB) in patients over 75 years of age were analysed. The three most frequent histological types were: Overall: membranous nephritis (MN), minimal change disease (MCD) and IgA Nephropathy (IgAN); In nephrotic syndrome (51% of RB): MN (36%), MCD (33%) and amyloidosis (12%); In chronic renal failure without nephrotic syndrome (25% of RB): chronic interstitial nephritis (17%), benign nephrosclerosis (12%) and IgAN (12%); In acute or progressive renal failure (18% of RB): acute tubular necrosis (36%), crescentic GN (16%) and IgAN (12%). Isolated proteinuria was most frequently associated with IgAN. In only 40% of patients was the medical history relevant, and only in selected cases it allowed for accurate prediction of the histological findings. Our data favor a more liberal use of biopsy in the elderly patients.     

Determination of optimal blood pressure for patients with IgA nephropathy based on renal histology.

To evaluate the optimal BP control for patients with IgA nephropathy (IgAN) based on the histologic severity of the nephropathy and the degree of renal dysfunction. We analyzed 332 consecutive renal biopsy specimens and clinical data from patients with IgAN. Patients were divided into three groups based on their BP at the time of biopsy: an optimal BP (SBP<120 mmHg and DBP<80 mmHg), a hypertensive BP (SBP > or = 140 mmHg and/or DBP > or = 90 mmHg), and an intermediate BP group. Each biopsy specimen was evaluated for mesangial proliferation, degree of sclerosis and/or hyalinosis of the arterioles and the interlobular artery using a semiquantitative method. Creatinine clearance and the percentage of sclerosed glomeruli were also determined. Both the degree of renal dysfunction and the histologic changes correlated significantly with BP, even in patients with a BP <140/90 mmHg. The patients with an optimal BP at the time of biopsy had significantly less histologic damage with respect to mesangial proliferation and vessel changes than those with an intermediate or hypertensive BP. In the patients with a hypertensive BP, the percentage of sclerotic glomeruli was significantly higher and the creatinine clearance was significantly lower. The optimal BP proposed by the WHO in 1999 prevents histologic evidence of renal damage for patients with IgAN.     

Existence and significance of hepatitis B virus DNA in kidneys of IgA nephropathy

AIM: To investigate the existence and significance of hepatitis B virus (HBV) DNA in the pathogenesis of IgA nephropathy (IgAN). METHODS: Fifty cases of IgAN with HBV antigenaemia and/or hepatitis B virus antigens (HBAg, or HBsAg, HBcAg) detected by immunohistochemistry in renal tissues were enrolled in our study. The distribution and localization of HBV DNA were observed using in situ hybridization. Southern blot analysis was performed to reveal the state of renal HBV DNA. RESULTS: Among the 50 patients with IgAN, HBs antigenemia was detected in 17 patients (34%). HBAg in renal tissues was detected in 48 patients (96%), the positive rate of HBAg, HBsAg, and HBcAg was 82% (41/50), 58% (29/50), and 42% (21/50) in glomeruli, respectively; and was 94% (47/50), 56% (28/50) and 78% (39/50) in tubular epithelia, respectively. Positive HBV DNA was detected in 72% (36/50) and 82% (41/50) cases in tubular epithelia and glomeruli respectively by in situ hybridization, and the positive signals were localized in the nuclei of tubular epithelial cells and glomerular mesangial cells as well as infiltrated interstitial lymphocytes. Moreover, 68% (34/50) cases were proved to be HBV DNA positive by Southern blot analysis, and all were the integrated form. CONCLUSION: HBV infection might play an important role in occurrence and progress of IgAN. In addition to humoral immune damages mediated by HBAg-HBAb immune complex, renal tissues of some IgAN are directly infected with HBV and express HBAg in situ, and the cellular mechanism mediated by HBV originating from renal cells in situ may also be involved in the pathogenesis of IgAN.     

Clinical features and natural history of IgA nephropathy.

IgA nephropathy (IgAN) is the most common form of glomerulonephritis worldwide. It is characterized by recurrent gross hematuria, microhematuria and/or proteinuria and diffuse mesangial IgA deposits in glomeruli. It is predominantly a disease of young males. Apart from primary IgAN (Berger's disease), IgA deposits in the glomeruli are also seen in Henoch-Sch?nlein purpura and in association with various of other diseases, particularly liver cirrhosis. Originally it was thought that IgAN was a benign disease, but it is now known that approximately 20-40% of patients develop progressive renal disease 5 to 25 years after diagnosis and progress to end-stage renal disease. Clinical predictors of progressive disease are elevated serum creatinine concentration at presentation, increased systemic blood pressure, persistent protein excretion > 1.0 g/day and histological predictors are glomerulosclerosis, tubular atrophy/interstitial fibrosis, extension of immune deposits to the perivascular space and crescent formation. Progression correlates more closely with the severity of tubulointerstitial lesions than with the degree of glomerular lesions. These features of IgAN reported in literature were mostly, but not completely, confirmed by analysis of all consecutive patients with biopsy proven IgAN and follow-up > 12 months in the renal units of Heidelberg and Prague using univariate analysis, multiple range test and multiple regression analysis.     

粘附分子P选择素在老年肾病综合征患者肾组织中的表达和周围血流式细胞分析

目的：探讨粘附分子Ｐ选择素（ＣＤ６２Ｐ）在老年肾病综合征（ＮＳ）中的变化。方法：采用流式细胞术和直接免疫荧光标记单克隆抗体对老年ＮＳ患者周围血和肾活检组织进行了ＣＤ６２Ｐ表达的研究。结果：①２６例老年ＮＳ患者周围血ＣＤ６２Ｐ表达量较正常组显著增高（Ｐ＜０．０１）；②肾组织中显示ＣＤ６２Ｐ表达２２例（８４．６２％），表达部位常见于肾小球系膜区、血膜袢，其次为肾小管、间质小血管及球囊壁。③ＣＤ６２Ｐ在周围血表达水平与肾组织表达程度呈显著正相关（Ｐ＜０．０１），血、肾组织的表达与患者尿蛋白定量呈正相关（Ｐ＜０．０５）。结论：ＣＤ６２Ｐ在老年ＮＳ患者肾组织和周围血中表达增强，提示其在ＮＳ发病机制中具有重要作用