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中华肾病研究电子杂志

中华肾病研究电子杂志 ›› 2017, Vol. 06 ›› Issue (02) : 58 -63. doi: 10.3877/cma.j.issn.2095-3216.2017.02.003

所属专题： 文献；

论著

狼疮肾炎肾小管间质损伤的临床特点及其对预后的影响
张岩1, 蔡广研1,†(), 刘述文1, 张雪光1, 寇佳1, 陈仆1, 吴杰1, 孟金铃1, 尹忠1, 张利1, 陈香美1   
  1. 1. 100853　北京，解放军总医院肾脏病科、解放军肾脏病研究所、肾脏疾病国家重点实验室、国家慢性肾病临床医学研究中心
  • 收稿日期:2016-10-28 出版日期:2017-04-28
  • 通信作者: 蔡广研

Clinical characteristics of tubulointerstitial lesions and their impacts on prognosis of lupus nephritis

Yan Zhang1, Guangyan Cai1,†(), Shuwen Liu1, Xueguang Zhang1, Jia Kou1, Pu Chen1, Jie Wu1, Jinling Meng1, Zhong Yin1, Li Zhang1, Xiangmei Chen1   

  1. 1. Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing 100853, China
  • Received:2016-10-28 Published:2017-04-28
  • Corresponding author: Guangyan Cai
  • About author:
    Corresponding author: Cai Guangyan, Email:
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引用本文：

张岩, 蔡广研, 刘述文, 张雪光, 寇佳, 陈仆, 吴杰, 孟金铃, 尹忠, 张利, 陈香美. 狼疮肾炎肾小管间质损伤的临床特点及其对预后的影响[J]. 中华肾病研究电子杂志, 2017, 06(02): 58-63.

Yan Zhang, Guangyan Cai, Shuwen Liu, Xueguang Zhang, Jia Kou, Pu Chen, Jie Wu, Jinling Meng, Zhong Yin, Li Zhang, Xiangmei Chen. Clinical characteristics of tubulointerstitial lesions and their impacts on prognosis of lupus nephritis[J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2017, 06(02): 58-63.

目的

了解狼疮肾炎肾小管间质损伤的临床特点及其对预后的影响。

方法

收集1990年1月1日至2011年6月30日在解放军总医院肾脏病科经肾活检确诊为狼疮肾炎的309例患者的临床及病理资料，所有患者均符合1997年美国风湿病学会推荐的系统性红斑狼疮(SLE)分类标准。采用2003年国际肾脏病协会及肾脏病理学会修订的狼疮肾炎病理分型标准对所有患者进行重新病理分型。计算该组狼疮肾炎肾间质炎细胞浸润、肾小管萎缩、间质纤维化、肾小管上皮细胞变性的发生率；采用秩和检验分析不同类型狼疮肾炎之间肾小管间质损伤的差异及发生病理转型的Ⅳ型狼疮肾炎转型前后肾小管间质损伤的差异。采用Kaplan-Meier曲线分析肾小管间质损伤对狼疮肾炎预后的影响。

结果

①本组狼疮肾炎病例中肾间质出现炎细胞浸润、肾小管萎缩、间质纤维化、肾小管上皮细胞变性的比例分别为86.5%，66.5%，66.9%和55.1%。②不同类型的狼疮肾炎其间质炎细胞浸润、肾小管萎缩、间质纤维化程及肾小管上皮细胞变性程度不同(均P﹤0.05)；其中，Ⅲ型和Ⅳ型狼疮肾炎患者肾小管间质损伤较重(χ2＝13.857, P<0.001)。本组病例中有47例IV型狼疮肾炎患者行重复肾活检，其中有14例在第二次肾活检时转为Ⅱ型(29.7%)，但其重复肾活检时间质炎细胞浸润、肾小管萎缩、间质纤维化及肾小管上皮细胞变性程度与转型前比较差异无统计学意义(均P>0.05)。③间质炎细胞浸润、肾小管萎缩及间质纤维化可影响患者的预后，病变越重，预后越差(均P﹤0.001)；而各种程度的肾小管上皮细胞变性对患者预后无影响(P＝0.07)。

结论

狼疮肾炎肾小管间质损伤发生率高，不同类型的狼疮肾炎的肾小管间质病变程度不同。肾小管间质损伤程度不影响IV型狼疮肾炎的病理转型，且病理转型前后肾小管间质损害改变不明显。肾小管间质损伤可影响患者的预后，损伤越重预后越差。

关键词: 狼疮肾炎, 肾小管间质损伤, 预后
Objective

To investigate the clinical characteristics of tubulointerstitial lesions (TIL) and their impacts on prognosis of lupus nephritis.

Methods

Three hundred and nine patients with lupus nephrits from the Department of Nephrology, Chinese PLA General Hospital, were confirmed by renal biopsy. Clinical and pathological parameters of this cohort were collected. All patients were reviewed and reclassified according to the 2003 Classification System of International Society of Nephrology (ISN)/Renal Pathology Society (RPS). Semiquantitative score was used to assess the severity of renal injury. Kaplan-Meier curve was used to analyze the outcomes of patients with different TIL.

Results

The percentages of interstitial inflammatory cells infiltration, tubular atrophy, interstitial fibrosis, and tubular epithelial cell degeneration were 86.5%, 66.5%, 66.9%, and 55.1%, respectively. Class Ⅱ, Ⅲ, Ⅳ, and Ⅴ lupus nephritis were different from each other in the interstitial inflammatory cells infiltration, tubular atrophy, interstitial fibrosis, and tubular epithelial cell degeneration (all P<0.05). The severity of TIL in class Ⅲ and Ⅳ lupus nephritis were more severe than those in class Ⅱ and Ⅴ (χ2 =13.857, P﹤0.001). 47 patients with class Ⅳ lupus nephritis received repeat-biopsies, among whom 14 cases transformed to class Ⅱ, but the differences in interstitial inflammatory cells infiltration, tubular atrophy, interstitial fibrosis, and tubular epithelial cell degeneration were not significant (all P>0.05). The interstitial inflammatory cells infiltration, tubular atrophy, and interstitial fibrosis were associated with the patients′ prognosis: the more severe TILs, the poorer prognosis (all P<0.001).

Conclusions

The incidence of TILs in lupus nephritis was high. TILs in different classes of lupus nephritis were different from each other. The degree of TILs did not affect the pathological transformation of class IV lupus nephritis, and the changes of TILs before and after pathological transformation were not obvious. TILs may predict the renal outcomes: the more severe TILs, the poorer prognosis.

Key words: Lupus nephritis, Tubulointerstitial lesions, Prognosis
表1 309例狼疮肾炎患者临床特征及病理数据
项目 例数(%)或(±s)
女性 242(78.32)
年龄(岁) 31.18±11.72
高血压 120(38.83)
大量蛋白尿 141(45.63)
血尿 226(73.14)
贫血 232(75.08)
血小板减少 50(16.18)
白细胞减少 70(22.65)
血清肌酐升高 110(35.60)
高脂血症 224(72.49)
低补体 267(86.41)
抗核抗体阳性率a 239/289(82.70)
抗ds-DNA抗体阳性率b 127/251(50.60)
活动性指数 6.09±3.89
慢性化指数 3.00±2.70
细胞增殖 1.94±0.86
肾小球白细胞浸润 0.84±0.81
袢坏死和(或)核碎裂 0.90±1.35
微血栓 0.19±0.51
细胞性新月体 1.05±1.65
球性硬化 0.66±0.85
纤维性新月体 0.21±0.53
间质炎细胞浸润 1.40±0.89
肾小管上皮细胞变性 0.33±0.52
肾小管萎缩 1.04±0.98
间质纤维化 1.06±0.98
血管壁增厚 0.64±0.99
透明样变 0.06±0.27
纤维素样坏死 0.03±0.25
表2 各型狼疮肾炎小管间质损伤评分比较(±s)
项目 间质炎细胞浸润 肾小管萎缩 间质纤维化 肾小管上皮细胞变性
Ⅱ型 0.70±0.59 0.45±0.56 0.42±0.61 0.36±0.60
Ⅲ型 1.28±0.65 1.21±0.62 1.07±0.75 0.69±0.76
Ⅳ型 1.66±0.92 1.22±1.08 1.27±1.05 0.91±0.93
Ⅴ型 0.96±0.51 0.64±0.68 0.64±0.62 0.71±0.71
t值 41.30 40.27 25.99 11.60
P值 <0.001 0.003 <0.001 0.018
图1 各型狼疮肾炎肾小管间质病变程度分布
表3 狼疮肾炎Ⅳ型两次肾活检相关指标的比较(±s)
组别 例数 转为Ⅱ型的患者
间质炎细胞浸润 肾小管萎缩 间质纤维化 肾小管上皮细胞变性 AI CI
首次 14 1.33±0.72 0.73±0.80 0.93±0.70 1.00±0.76 8.67±4.01 2.27±2.15
重复 14 1.00±0.65 0.93±0.59 0.93±0.59 2.53±0.92 2.53±0.92 2.53±1.60
t值 ? 1.810 0.966 0.287 1.164 3.904 1.149
P值 ? 0.096 0.317 0.799 0.291 0.002 0.250
组别 例数 维持Ⅳ型或转为Ⅲ型的患者
间质炎细胞浸润 肾小管萎缩 间质纤维化 肾小管上皮细胞变性 AI CI
首次 33 1.81±0.79 1.17±0.90 1.25±0.94 1.24±0.92 9.31±3.69 3.33±2.45
重复 33 1.61±0.87 1.47±0.91 1.56±0.91 1.09±0.90 5.36±2.74 4.83±0.91
t值 ? 0.736 0.810 1.160 0.345 4.460 2.17
P值 ? 0.469 0.418 0.246 0.730 ﹤0.001 0.03
t值1 ? 1.726 1.312 0.987 0.692 0.312 1.022
P值1 ? 0.073 0.171 0.324 0.531 0.604 0.235
表4 狼疮肾炎肾小管间质不同病变对肾脏预后的影响
? 评分 例数 删失数 百分比 中位生存时间(月) 标准误 95%置信区间 P值
低 高
间质炎细胞浸润 0 16 14 87.5 180 0 － － ﹤0.001
1 34 24 70.6 196 68.713 61.322 330.678
2 22 10 45.5 108 32.707 43.895 172.105
3 13 2 15.4 20 11.504 0.000 42.547
肾小管萎缩 0 40 32 80 196 0 － － ﹤0.001
1 25 13 52 168 46.874 76.127 259.873
2 10 4 40 25 26.089 0 76.134
3 10 1 10 20 18.974 0 51.188
间质纤维化 0 36 29 80.6 180 － － － ﹤0.001
1 30 16 53.3 196 60.009 78.383 313.617
2 10 5 50 48 － － －
3 9 0 0 20 11.926 0.000 43.374
小管上皮细胞变性 0 39 27 69.2 180 75.083 32.837 327.163 0.07
1 33 18 54.5 196 59.861 32.837 313.327
2 9 4 44.4 96 53.666 0.000 201.18
53 3 0 0 36 27.761 0.000 90.411
图2 狼疮肾炎患者肾小管间质不同病变对肾脏预后的影响
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