用户名: 密码: 验证码:
狼疮性肾炎临床表现与病理研究
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
目的探讨狼疮性肾炎(Lupus Nephritis, LN)患者的临床表现和免疫学特点,狼疮临床活动性指标与病理分型和改变之间的关系,以进一步认识LN的病变特点,提高临床诊断与治疗水平。
     方法回顾性分析1993年4月-2009年10月期间在复旦大学附属中山医院经肾活检明确诊断为LN的227例患者的临床、实验室及病理学资料,以及同期住院的778例SLE患者的资料,采用方差分析、秩和检验和卡方检验对各项临床表现、实验室指标、免疫学指标、狼疮活动性指标与病理分型等进行描述和分类统计,以多元线性回归进行相关分析。
     结果
     1.一般情况
     (1)1993年4月-2009年10月住院治疗的SLE患者778例,其中男性75例,女性703例,男女比例1:9.4;经肾活检确诊LN患者227例,其中男性28例,女性199例,男女比例1:7.1;虽然LN的男性患者比例稍高于SLE患者,但两者间无明显差异(P=0.263)
     (2) SLE患者的发病年龄为37.62±13.54(10-80)岁,男性发病年龄早于女性患者(P=0.020);确诊LN患者的发病年龄为34.41±11.86(13-75)岁。男、女LN患者的平均发病年龄无明显统计学差异(P>0.05)。
     2.病理类型
     根据WHO国际肾脏病学会/肾脏病理学会(ISN/RPS)狼疮性肾炎分型,轻微病变型(Ⅰ型)28例(12.3%),系膜增生型(Ⅱ型)29例(12.8%),局灶节段型(Ⅲ型)41例(18.1%),弥漫增生型(Ⅳ型)85例(37.5%),膜型(V型)38例(16.7%),硬化型(Ⅵ型)6例(2.6%)。其中Ⅳ型LN比例最高,其次为Ⅲ型。男女患者在各型LN病理类型中的分布无显著性差异(P=0.626)。
     3.临床表现
     (1)分别以尿蛋白定量0.5g/24小时或+++(标准①)及0.3g/24小时或+(标准②)为界,可伴有管型(红细胞、血红蛋白、颗粒或混合管型)和/或肾功能不全;并排除其他原因引起的尿和肾功能异常定义为肾脏损害,本研究778例SLE患者按标准①1有肾脏损害表现者441例(57.6%),以肾外损害为主要表现者337例(43.3%);按标准②有肾脏损害表现者508例(65.3%),以肾外损害为主要表现者270例(34.7%)。
     (2)确诊的LN患者中单纯血尿36例(15.9%),单纯蛋白尿81例(35.7%),血尿合并蛋白尿110例(48.4%),表现为肾病综合征大量蛋白尿53例(23.4%),肾功能减退37例(16.3%)。
     (3)Ⅳ型LN患者临床表现多样,以血尿合并蛋白尿、肾病综合征大量蛋白尿及肾功能减退最多见(P=0.000);表现为单纯蛋白尿的以V型LN患者较常见,但各型比较无明显差异(P=0.081)。
     (4)肾外表现中面部红斑、关节炎的发生率以Ⅱ型最高(P=0.004);CNS损害共6例,分别见于Ⅱ型、Ⅲ型、Ⅳ型,而Ⅰ型和Ⅴ型未发现CNS损害;而光敏、口腔溃疡、浆膜炎、血液系统累及等症状在各型中的发生率无统计学差异(P>0.05)。
     (5)LN患者中高血压的发病率24.2%,以Ⅳ型发病率最高(P<0.05)。
     4.实验室指标
     (1)有肾脏损害表现患者血红蛋白、血白蛋白水平低于无肾脏损害表现患者,而有肾脏损害表现患者的血肌酐水平明显高于无肾脏损害表现患者(P=0.000);不同病理类型的LN患者血红蛋白、血小板、血白蛋白、血肌酐比较总体有差异(P<0.05或0.01),Ⅳ型LN表现最有特征性:即Ⅳ型LN患者24小时尿蛋白定量最多,血肌酐水平最高;而血红蛋白、血小板、血白蛋白水平最低。
     (2) SLE患者的ANA型态以颗粒型最多,均质型次之;有肾脏损害表现的SLE患者ds-DNA抗体滴度明显高于无肾脏损害表现患者(P=0.011);有肾脏损害表现的SLE患者抗核小体抗体(AnuA)阳性率高于无肾脏损害表现患者(P=0.032);不同病理类型的LN患者间自身抗体阳性率无明显差异(P>0.05)。
     (3)有肾脏损害表现患者其补体降低的发生率高于无肾脏损害表现患者,且降低的程度亦更明显;LN患者以Ⅳ型补体降低的最明显(P<0.05)。
     (4)不同病理类型LN患者SLEDAI、AI、CI评分及LACC评分均以Ⅳ型最高(P<0.01)。
     5.临床表现、实验室指标与病理类型的相关性分析
     血红蛋白和补体水平与SLEDAI负相关;24小时尿蛋白定量和血肌酐与AI评分正相关,补体C3水平与AI评分负相关;血肌酐水平与CI评分正相关。
     结论
     1.SLE和LN患者的好发年龄在30-50岁,女性患病率远高于男性。
     2.SLE患者临床有肾脏损害表现约占三分之二;LN患者的病理类型中,Ⅳ型最为多见,占整个LN的三分之一以上,且肾脏损害表现最突出。
     3.LN患者以血尿合并蛋白尿表现最常见,约占整个LN的一半;以肾病综合征起病者约占四分之一;约有六分之一的LN患者表现为肾功能减退。
     4.SLE有肾脏损害表现患者血红蛋白、血白蛋白水平低于无肾脏损害表现患者;而血肌酐水平明显高于无肾脏损害表现患者。Ⅳ型LN患者贫血、低蛋白血症、低补体C3血症、肾功能不全的发生率及严重程度显著高于其他各型,活动性指数(AI、CI、SLEDAI、LACC)亦最高。
     5.SLE有肾脏损害表现者抗核小体抗体阳性率显著高于无肾脏损害表现者,且ds-DNA抗体滴度明显增高。而自身抗体在不同LN病理类型的患者之间无明显差异(P>0.05)。
     6.血红蛋白和补体水平与SLEDAI负相关;24小时尿蛋白定量和血肌酐水平与AI评分正相关,补体C3水平与AI评分负相关;血肌酐水平与CI评分正相关。
     7.SLE常累及肾脏,LN的临床表现和实验室指标与其病理类型存在一定的联系,根据临床表现和实验室指标可以在一定程度上评估LN的严重程度,但是仍不能替代肾活检在LN病理诊断中的重要价值。
Objective:To analysis the relationship between clinical feathers and immunological characteristics, activity index of systemic lupus erythematosus (SLE) and renal pathological classifications in lupus nephritis (LN), to investigate the characteristics of LN, and to improve the basis for the diagnosis and treatment.
     Methods:The clinical and pathological data of 227 patients with LN were analyzed retrospectively, controlled by 778 patients with SLE in the same period. We used Kruskal-Wallis H test to investigate the relationships of the clinical and pathological features. Comparisons between different pathological classifications were by the chi-square method and a multiple linear regression.
     Results:
     1. General situation:
     (1) 778 cases of SLE patients,75 male and 703 female, the ratio of male and female patients is 1:9.4. The renal biopsy confirmed 227 cases of LN patients,28 male and 199 female, the ratio of male and female patients is 1:7.1
     (2) The mean onset age of SLE patients is (37.62±13.540) years (10-80years), the onset age of male patients is earlier than that of female patients (P=0.020). The mean onset age of confirmed LN patients is (34.41±11.86) years (13-75 years), there is no significant difference between male patients and female patients (P>0.05).
     2. Pathological types:the renal pathological types show typeⅠ12.3%; typeⅡ12.8%; typeⅢ18.1%; typeⅣ37.5%; typeⅤ16.7%; typeⅥ2.6%. TypeⅣwith the highest proportion, which followed by typelll.
     3. Clinical manifestations:
     (1) In 778 cases of SLE patients, there are 441 patients manifested by kidney injury, while 337 patients without kidney injury. In 227 cases of LN patients, hematuria only is 36 cases, proteinuria only is 81 cases, while hematuria combined with proteinuria is 110 cases. Manifested by nephritic syndrome is 53 cases, renal dysfunction is 37 cases.
     (2) TypeⅣLN is mainly showed as hematuria combined with proteinuria or nephritic syndrome, and even showed as renal dysfunction (P=0.000); TypeⅤLN showed as proteinuria only for common.
     (3) As respect to the outer-renal symptoms, the incidence of facial erythema and arthritis was highest in typeⅡLN (P=0.004). While the photosensitive, oral ulcers, serositis and blood system involved with no statistical difference.
     (4) The incidence of hypertension is 24.2%, type IV has the significant difference compared with other types.
     4. Laboratory parameters
     (1) Average hemoglobin (HGB) levels of patients with kidney injury lower than those without kidney injury, while serum creatinine (Scr) levels of patients with kidney injury is significantly higher than that of without kidney injury (P=0.000). Patients of type IV LN is with the most prominence
     (2) ANA patterns of SLE patients is most showed as particle type, followed by homogenous type. Positive rate of anti-nucleosome antibodies in SLE patients with kidney injury is higher than patient without kidney injury. And the ds-DNA antibody titer is significantly higher than the patient without kidney injury (P=0.011).
     (3) Anti-nuclear antibody series in every type are in general no significant difference (P>0.05).
     (4) AI、CI and SLEDAI scores are the highest in type IV LN compared with other types. LACC standard reflects the limitation combined with SLEDAI standard.
     5. Correlation analysis of clinical and pathological types:Hemoglobin and complement level are negative correlation with the SLEDAI score; urine protein and serum creatinine level are positive correlation with the AI score, while complement level is negative correlation with the AI score; serum creatinine level is positive correlation with the CI score. Pathological types are correlated with age, C3 level, SLEDAI score, AI score and CI score.
     Conclusion:
     1. The prevalence of SLE and LN are highest in 30-50 years old. The prevalence in female is much higher than male.
     2. The most prevalent type in LN patients is type IV LN with the most severe laboratory indicators.
     3. TypeⅣLN has the highest incidence of anemia, hemouria, proteinuria and complement decrease, and the active index is the highest.
     4. Positive rate of anti-nucleosome antibodies in SLE patients with kidney injury is higher than patient without kidney injury. Anti-nuclear antibody series in each type are in general no significant difference.
     5. Hemoglobin and complement level are negative correlation with the SLEDAI score; urine protein and serum creatinine level are positive correlate with the AI score, while complement 3 level is negative correlation with the AI score; serum creatinine level is positive correlation with the CI score. Pathological types are correlated with age, C3 level, SLEDAI score, AI score and CI score.
引文
[1]Haddouk S, Ben AyedM, Baklouti S, et al. Clinical significance of anti-nucleosome antibodies in Tunisian systemic lupus erythematosus patients. Clin Rheumatol,2005,24 (3):219-222.
    [2]Simon JA, Cabiedes J, Ortiz E, et al. Anti-nucleosome antibodies in patients with systemic lupus erythematosus of recent onset. Potential utility as a diagnostic tool and disease activity marker. Rheumatology (Oxford),2004,43 (2):220-224.
    [3]Ghirardello A, Doria A, Zampieri S, et al. Antinucleosome antibodies in SLE:a two-year follow-up study of 101 patients. J Autoimmun,2004,22 (3):235-240.
    [4]刘笑芬,黄英伟.狼疮性肾炎的病理与临床关系[J].临床肾脏病杂志,2002,2(2):55-57.
    [5]张明辉,刘艳辉,骆新兰.狼疮性肾炎144例临床和病理分析[J].广州医学,2009,3(30):453-456.
    [6]Li LS, Liu ZH. Epidemiologic data of renal diseases from a single unit in China:Analysis based on 13519 renal biopsy. Kidney Int,2004,66:920-923.
    [7]Glassack RJ, Cohen AH, Alder SG, et al. Secondary glomerular disease. In Brenner BM, Rector FC [M]. The kidney,1991,4:1280-1298.
    [8]叶任高,沈清瑞,主编。肾脏病诊断与治疗[M].北京人民卫生出版社,1995:271-280.
    [9]Cervera R, Khamashta MA, Font J, et al. Morbidity and mortality in systemic lupus erythematosus during a 10-year period:a comparison of early and late manifestations in a cohort of 1,000 patients. Medicine (Baltimore),2003,82(5):299-308.
    [10]胡伟新,刘春蓓,孙海鸥,等.1352例狼疮性肾炎的临床与免疫学特征.肾脏病与透析肾移植杂志,2006,15(5):401-408.
    [11]Baldwin DS, Lowenstein J, Rothifield NF, et al. The clinical course of the proliferative and membranous forms of lupus nephritis. Ann Intern Med,1970,73:929-942.
    [12]陶凤舞,廖履坦,吴兆龙,等.弥漫性增殖型狼疮性肾炎41例临床与病理分析[J].中华肾脏病杂志,1994,10(4):221.
    [13]Nossent HC, Henzan-Logmans SC, Vroom TM, et al.Contribution of renal biopsy data in predicting outcome in lupus nephritis, analysis of 116 patients[J]. Arthritis Rheum,1999,33:970.
    [14]James E. Balow and Howard A. Austin Ⅲ. Progress in the treatment of proliferative lupus nephritis. Current Opinion in Nephrology and Hypertension,2000,9:107-115
    [15]李敛,吴雄飞,等.1096例肾脏活检病理类型总结.重庆医学,2006,35(18):1676-1678.
    [16]Appel GB, Silva FG, PiraniCL,et al. Renal involvement in systemic lupus erythematosus (SLE):A study of 56 patients emphasizing histologic classification. Medicine,1978,75:371-410.
    [17]Najafi CC, Korbet SM, Lewis EJ, et al, Significance of histologic patterns of glomerular injury upon long term prognosis in severe lupus glomerulonephritis. Kidney Int,2001,59(6): 2156-2163.
    [18]高红宇,吕永曼,邵菊芳等.58例狼疮性肾炎病理与临床分析.临床内科杂志,2002,19(5):362.365.
    [19]Lewis EJ, Schwartz MM. Pathology of lupus nephritis. Lupus 2005;14:31-38
    [20]王海燕.肾脏病学.第2版.北京:人民卫生出版社,2001.861—881
    [21]刘笑芬,黄英伟,等.狼疮性肾炎的病理与临床关系[J].临床肾脏病杂志,2002,2(2):55-57
    [22]Cervera R, Khamashta MA, Font J,et al. Systemic lupus erythmatosus:Clinical and immunologic patterns of disease expression in a cohort of 1000 patients. Medicine,1993,72(2): 113-124.
    [23]傅辰生,徐元钊,张志刚,等.狼疮性肾炎的预后影响因素.上海医科大学学报,2000,27(5):371-374.
    [24]陈楠,李晓,狼疮性肾炎的临床特点与病理特征.诊断学理论与实践.2004,3(4):240-242.
    [25]Nossent HC, Henzen-Logmans SC, Vroom TM, et al. Contribution of renal biopsy data in predicting outcome in lupus nephritis,analysis of 116 patients. Arthris Rheum 1990;33:970.
    [26]王强,徐元钊,李明等.狼疮性肾炎患者的临床表现与病理类型的相关分析.中国麻风皮肤病杂志,2003,19(6):527-53。
    [27]姚凤祥,麻世迹,陈阳.·现代风湿病学·.北京:人民军医出版社,1995,224~227
    [28]徐建华,徐胜前,王芬,等.系统性红斑狼疮血清免疫学指标与疾病活动关系.安徽医学,1996,17(6):13
    [29]杨廷彬,严学念,·实用免疫学·长春:长春出版社185~186.
    [30]李义德,张玉蓉,王刚等,ANA、抗ds-DNA、抗ENA多肽抗体谱联合检测对SLE的临床诊断价值[J].宁夏医学杂志,2001,23(11):646~647
    [31]李碧清,黄世峰,等.SLE抗核抗体核型与受损脏器关系的探讨.重庆医学,2004,33(11):1086-1087.
    [32]李义德,张玉蓉,王刚等,ANA、抗ds-DNA、抗ENA多肽抗体谱联合检测对SLE的临床诊断价值[J].宁夏医学杂志,2001,23(11):646~647
    [33]谢红付,刘稚然,朱武等,ANA对SLE诊断与活动性的研究.湖南医科大学学报,1977,22(2):177-178.
    [34]Chubick AC,et al.An appraisal of tests for native DNA antibody in connective tissue disease.Ann Intern Med,1998,89:186.
    [35]Okamura M, Kanayama Y, Amastu K, et al. Significance of enzyme linked immunosorbent assay(ELISA) for antibodies to double stranded and single stranded DNA in patient with lupus nephritis correlation with severity of renal histology. Ann of Rheum Dis,1993,52:14
    [36]Raz E, Brezis M, Rosemann E, et al.Antibodies bind directly to renal antigen and induce kidney dysfunction in the isolated perfused rat kidney.J Immunol,1989,142:3076
    [37]Wallace DJ,et al.Lupus Erythematosus.5thed.Baltimore:Williams,1997,383~523
    [38]Bengtsson A, Nezlin R, Shoenfeld Y, et al. DNA levels in circulating immune complexes decrease at severe SLE disease activity:correlation with complement component Clq. J Autoimmun,1999,13(1):111-119
    [39]Williams RC, Malone CC, Miller RT, et al. Urinary loss of immunoglobulin G anti-F(ab) 2 and anti-DNA antibody in systemic lupus erythematosus nephritis. J Lab Clin Med, 1998,132(1):210-222
    [40]Macanovic M, HogarthMB, Lachmann PJ. Anti-DNAantibodies in the urine of lupus nephritis patients. Nephrol Dial Transplant,1999,14(2):1418-1424
    [41]Luger K, Macler AW, Richmond RK. Crystal structure of the nucleosome core paticle at 2.8 resolution. Nature,1997,389:251-261.
    [42]Berden JH. Lupus nephritis:consequence of disturbed removal of apoptotic cells? Neth J Med,2003,61:233-238.
    [43]Chairns AP, McMillan SA, Crtckard AD, et al. Antinucleosome antibodies in the diagnosis of systemic lupus erythematosus. Ann Rheum Dis,2003,62:272-273.
    [44]苏茵,韩蕾,栗占国等,抗核小体抗体测定在系统性红斑狼疮诊断中的意义.中华风湿病学杂志,2003,7:474-477.
    [45]Berden JH, Grootscholten C, Jurgen WC, et al. Lupus nephritis:a nucleosome waste disposal defect? J Nephrol,2002,15:Sl-10.
    [46]许柯,李小峰,胡学芳等,系统性红斑狼疮血清抗核小体抗体水平及意义的探讨.[J]中华风湿病杂志,2005,9:72-76.
    [47]Ho A, Barr SG, Magder LS, et al. A decrease in complement is associated with increased renal and hematologic activity in patients with systemic lupus erythematosus. Arthritis Rheum 2001; 44:2350-2357.
    [48]Stoll T, Stucki G, Malik J, et al. Further validation of the BILAG disease activity index in patients with systemic lupus erythematosus. Ann Rheum Dis 1996;55:756-760.
    [49]Belmont HM, Buyon J, Giorno R, et al. Up-regulation of endothelial cell adhesion molecules characterizes disease activity in systemic lupus erythematosus. The Shwartzman phenomenon revisited. Arthritis Rheum 1994;37:376-383.
    [50]MollnesTE, HagaHJ, Brun JG, et al. Complement activation in patients with systemic lupus erythematosus without nephritis. Rheumatology 1999;38:933-940.
    [51]]何兰,唐中,张国元,系统性红斑狼疮患者血清中ANA、抗ds-DNA抗体、C3、C4之间关系分析.川北医学院学报,1997,12(4):34~35
    [52]马英,张道友,叶任高.670例系统性红斑狼疮的血清免疫分析[J].四川医学,1999,20(1):36-37
    [53]张红,尤崇革.系统性红斑狼疮患者IgG、IgA、IgM及补体C3检测结果分析[J].齐鲁医学检验,2004,15(2):56-57
    [54]尹培达.狼疮肾炎的治疗现状与展望.中华风湿病学杂志,2002,6(2):77-79.
    [55]余英豪,郑智勇,卢起炎.狼疮性肾炎组织形态学半定量分析及其临床意义.临床与实验病理杂志,1994,10(2):139.
    [1]陈香美,蔡广研.狼疮性肾炎治疗的新认识[J].临床内科杂志,2004,21(1):49-51
    [2]Weening JJ, D Agati VD, Schwartz MM, et al. The classification of glomerulonephritis in systemic lupus nephritis revisited[J].Kidney Int,2004,65(2):521
    [3]余学清.狼疮性肾炎的诊断与治疗[J].西藏医药杂志,2004,25(4):21-23
    [4]Zoja C,Liuxu. Renal expression of monocyte chemo attractant protein in lupus autoimmune[J]. JAm SocNephrol,1997,8:720-729.
    [5]Adams DH, Shaws S. Leukocyte endothelial interactions and regulation of leukocyte migration[J]. Lancet,1994,343:831.
    [6]Wada T, Furuichik.MCP21 alpha and MCP21 contribute to crescents and interstitial lesions in human crescentic glomerulonephritis[J]. Kidney Int,1999,56:995-1003.
    [7]Zoja C, corna D, BenedettiG,et al. Bindarit retards renal disease and prolongs survial in murine lupus autoimmune disease [J].Kidney Int,1998,53:726-734.
    [8]DaiC, LiuZ, zhou H,et al.Monocyte chemo attractant protein21 expression in renal tissue is associated with monocyte recruitment and tubulointerstitial lesions inpatients with lupus nephritis[J].Chin Med J (Engl),2001,114:864-886
    [9]Rovin BH, DoeN, Tan LC. Monocyte chemo attractant peotein21 Levels in patient with glomerular disease [J].Am J kidney Dis,1996,127:640-646.
    [10]陈玲,李军,齐悦,狼疮性肾炎患者血清MMP-3、MMP-9水平hin J Diffic and Compl Cas,2008,12(7):12
    [11]Kotajima L,Aotsuka S,Fujimani M,et al. Increased levels of matrix metallo proteinase23 in sera from patients with active lupus nephritis [J].Clin Exp Rheumatol,1998,16 (4):409-415.
    [12]陈伟英,阳晓,梁鸣,等.狼疮肾炎患者肾组织基质金属蛋白酶-3和-9的表达及其意义[J]
    中国危重病急救医学,2002,14(7):411-413.
    [13]黄玉成,李冬芹,王春燕,等.血清基质金属蛋白酶-3,-9的检测及其与系统性红斑狼疮活动性的关系[J].临床皮肤科杂志,2007,36(9):556-558.
    [14]Mishra J, Mori K, Ma Q, et al. Amelioration of ischemic acute renal injury by neutrohpil gelatinize-associated lipocalin [J]. J Am Soc Nephrol,2004,15(12):3073.
    [15]Hermine I.Brunner, Michelle Mueller, Alexei Grom, et al. Urinary Neutrophil Gelatinase-Associated Lipocalin as a Biomarker of Nephritis in Childhood-Onset Systemic Lupus Erythematosus[J]. Arthritis Rheum.2006, Aug;54(8):2577-84.
    [16]Xavier BOSCH, Antonio Guilabert, Josep Font. Antineutrophil cytoplasmicantibodies[J]. Lancet,2006,368(9533):404-418.
    [17]Ho JC,Curie A,Chun SL,et al. Clinical implications of antineutrophil cytoplasmic antibody test in lupus nephritis [J].Am J Nephrol,2003,20(1):57-63.
    [18]FauziAR,Kong NC,Chua MK,et al.Antibodies in systemic Lupus antineutrophil cytoplasmicery thematosus:prevalence, Disease activity correlation associations[J].Med J Malaysia,2004,59(3):372~377.
    [19]仲人前,范列英.自身抗体基础与临床[M].北京:人民军医出版社,2006.12-13.
    [20]钟旭辉,黄建萍,杨齐云,等.自身抗体与狼疮性肾炎的发病机制[J].临床儿科杂志,2006,24(4):25-30.
    [21]Harles PJ. Defective waste disposal:does it induce autoantibodies in SL E[J].Ann Rheum Dis,2003,62(1):1-31
    [22]Rrendelenburg M, Marfurt J, Gerber I, et al. Lack of occurrence of severe lupus nephritis among anti-Clq autoantibody-negative patients[J].Arthritis Rheumatol Assoc,2004,12:11-15.
    [23]Agrawal S. Lupus nephritis:an update on pathogenesis [J].Indian Rheumatol Assoc,2004,12:11-15.
    [24]Burlingame Rw, Cervera R. Anti-chromatin (anti-nucleosome) autoantibodies [J] Autoimmun Rev,2002,1(6):321-328.
    [25]Amoura Z, Koutouzov S, Piette JC.The role of nucleosomes in lupus [J].Arthritis Rheum,2000,12 (5):369-373
    [26]Berden JH,Grootscholten C,Jurgen WC,et al. Lupus nephritis:a nucleosome waste disposal defect [J].Nephrol,2002,15(suppl 6):1-101
    [27]陈楠,李晓.狼疮性肾炎的临床特点与病理特征[J].诊断学理论与实践,2004,3(4):240-242
    [28]刘红,丁小强.狼疮性肾炎的诊断和治疗进展.郑州大学学报(医学版).2008,43(5):861-864
    [29]刘俊铎,沈克勤,刘志红等.弥漫增生性狼疮性肾炎按血管病变为基础的病理分型探讨.肾脏病透析与肾移植杂志,1998,7(3):235
    [30]张健皎.狼疮性肾炎的诊断与治疗研究进展.昆明医学院学报.2007,10(5):124-125
    [31]Austin HA, Balow JE. Natural history and treatment of lupus nephritis. Semin Nephrol,1999,19(1):2
    [32]Steinberg AD,Steinberg SC.Long term preservation of renal function in patients with lupus nephritis receiving treatment that includes cyclophosphamide versus those treated with prednisone only[J]. Arthritis Rheum,1991,34 (8):945
    [33]Mok CC, Ying KY,Lau CS, et al. Treatment of pure membranous lupus nephropathy with prednisone and azathioprine:an open21abel trial [J]. Am J KidneyDis,2004,43(2):269。
    [34]Grcevska L, Popovska MM, Dzikova S, et al. Role of mycophenolate mofetil in the treatment of lupus nephritis [J].Ann N Y Acad Sci,2007,1110:433
    [35]邹原方,叶志中.狼疮性肾炎治疗的研究进展[J].社区医学杂志,2008,6(5):234-236
    [36]胡伟新.霉酚酸酯治疗狼疮性肾炎及血管炎展望.肾脏病与透析肾移植杂,1998,7(3):264
    [37]Ong LM, Hooi LS, Randomized controlled tral of pulse intravenous cyclophosphamide versus mycophenolate mofetil in the induction therapy of proliferative lupus nephritis [J].Nephrology(Carhton),2005.10(5):504-510
    [38]沈克勤,张景红,黎磊石等.小剂量泼尼松联合环孢素A治疗难治性狼疮性肾炎.中华内科杂志,1992,31(1):38
    [39]胡伟新章海涛来氟米特维持治疗狼疮性肾炎的临床疗效J Nephrol Dialy Transplant Vol.17,No.3,Jun.2008,224-226
    [40]Chow KM, Szeto CC. Leflunomide and antiglomerular basement membrane glomerulonephritis:comment on the letter by Bruyn[J].Arthritis Rheum,2004,50(l):336-337.
    [41]Tam LS, Ii EK, Wong CK, et al. Safety and efficacy of leflunonide in the treatment of lupus nephritis refraction or intolerant to traditional immunosuppressive therapy:an open label trial[J].Ann Rheum Dis,2006,65(3):417-418.
    [42]章海涛,胡伟新,谢红浪等.普乐可复与环磷酰胺诱导治疗Ⅳ型狼疮性肾炎的疗效比较[J].肾脏病与透析肾移植,2006,15(6):501-507.
    [43]MARUYAMA M, YAMASAKI Y, SADA K, et al. Good response of membranous lupus nephritis to tacrolimus [J]. Clin Nephrol,2006,65(4):276-279.
    [44]MOK C C, TONG K H, TO C H, et al. Tacrolimus for induction therapy of diffuse proliferative lupus nephritis:an open-labeled pilot study [J]. Kidney hit,2005,68(2):813-817.
    [45]徐安平,吕军,他克莫司治疗狼疮性肾炎的前瞻性研究Journal of Sun Yat-Sen University(Medical Sciences), Vol.28 No.6,Nov.2007,716-718
    [46]BoumpasDT, Furie R, Manzi S, et al. A short course of BG9588(antiCD40 ligand antibody) imp roves serologic activity and decrea2ses hematuria in patients with proliferative lupus glomerulonephritis[J]. Arthritis Rheum,2003,48:719-727.
    [47]Sfikakis PP, Boletis JN, Lionaki S, et al Remission of p roliferative lupus nephritis following B cell depletion therapy is p receded by down-regulation of the T cell costimulatory molecule CD40 lig2 and:an open-label trial[J]. Arthritis Rheum.2005,52 (2):501-513.
    [48]Smith KG, Jones RB, Burns SM, et al. Long-term comparison of rituximab treatment for refractory systemic lupus erythematosus and vasculitis:Remission, relapse, and re-treatment [J]. Arthritis Rheum,2006,54 (9):2970-2982
    [49]李红梅,沈汉超.狼疮性肾炎的病理分型与临床特点的分析.浙江医学,2005,27(8):578-569.
    [50]Burt RK. Arthritis Rheum, An appraisal of tests for native DNA antibody in connective tissue disease.1998;41(Suppl):s241
    [51]Strohel ES,Fritschka E,Schmitt Graff A,et al. Crystal structure of the nucleosome core
    paticle at 2.8 resolution Rheumatol Int,2000; 19(6):235
    [52]张雷,马红霞,冯冬梅,等.自体外周血造血干细胞移植治疗系统性红斑狼疮9例临床疗效探讨.河南医药信息,2002,10(1):154
    [53]Goral S, Ynares C, Shappell SB, et al. Recurrent lupus nephitis in renal transplant recipients revisited:It is not rare. Transplantation,2003,75(5):651-656

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700