【作者】 张怡；

【导师】 钟一红； 刘红；

【作者基本信息】 复旦大学 ， 内科学， 2010， 硕士

【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。更多还原

【Abstract】 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.更多还原