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[肾损伤分子(KIM-1、MCP-1)及IV型胶原在抗中性粒细胞胞浆抗体相关性肾小球肾炎活动度评估中的作用]

[Kidney injury molecules (KIM-1, MCP-1) and type IV collagen in the assessment of activity of antineutrophil cytoplasmic antibody-associated glomerulonephritis].

作者信息

Bulanov N M, Serova A G, Kuznetsova E I, Bulanova M L, Novikov P I, Kozlovskaya L V, Moiseev S V

机构信息

I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia, Moscow, Russia.

Vladimir Regional Clinical Hospital, Vladimir, Russia.

出版信息

Ter Arkh. 2017;89(6):48-55. doi: 10.17116/terarkh201789648-55.

Abstract

AIM

To assess the significance of determining the serum and urinary concentrations of monocyte chemotactic protein-1 (MCP-1), kidney injury molecule-1 (KIM-1), and type IV collagen in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) to estimate the activity of renal involvement in AAV.

SUBJECTS AND METHODS

78 patients (32 men and 46 women) (median age 55 (45; 61) years) with AAV were examined. The patients were divided into 3 groups according to the AAV activity estimated using the Birmingham vasculitis activity Score (BVAS): 1) 25 patients with active ANCA-associated glomerulonephritis (GN); 2) 26 patients with active AAV without renal involvement; 3) 27 patients in sustained AAV remission. The serum and urinary concentrations of the markers were measured by enzyme immunoassay.

RESULTS

The urinary concentration of all 3 biomarkers was higher in patients with renal involvement (Group 1); the differences in the levels of MCP-1 and type IV collagen were statistically significant as compared to Groups 2 and 3 (p<0.01), while that in KIM-1 level was only in Group 2. There were statistically significant correlations between the urinary concentration of these biomarkers and the traditional GN activity indices (erythrocyturia, daily proteinuria (DPU), total BVAS scores that reflect renal involvement, as well as serum creatinine levels and estimated glomerular filtration rate (p<0.05). ROC curve analysis showed that the urinary MCP-1 excretion of ≥159 pg/ml had the highest (92%) sensitivity and urinary type IV collagen excretion of ≥3.09 µg/l had the highest (86%) specificity in assessing the activity of ANCA-associated GN. At the same time, their diagnostic value increased in terms of a combination of DPU and ESR (96% sensitivity, 84.9% specificity).

CONCLUSION

The urinary excretion of MCP-1, KIM-1, and type IV collagen reflects the severity of local renal inflammation in AAV patients and a study of these indicators is a promising diagnostic tool for assessing the activity of ANCA-associated GN.

摘要

目的

评估测定抗中性粒细胞胞浆抗体(ANCA)相关血管炎(AAV)患者血清和尿液中单核细胞趋化蛋白-1(MCP-1)、肾损伤分子-1(KIM-1)及IV型胶原的浓度对于评估AAV肾受累活动度的意义。

对象与方法

对78例AAV患者(32例男性,46例女性)(中位年龄55(45;61)岁)进行检查。根据使用伯明翰血管炎活动评分(BVAS)评估的AAV活动度将患者分为3组:1)25例活动性ANCA相关肾小球肾炎(GN)患者;2)26例无肾受累的活动性AAV患者;3)27例AAV持续缓解患者。通过酶免疫测定法测量标志物的血清和尿液浓度。

结果

肾受累患者(第1组)中所有3种生物标志物的尿液浓度均较高;与第2组和第3组相比,MCP-1和IV型胶原水平的差异具有统计学意义(p<0.01),而KIM-1水平仅在第2组中有差异。这些生物标志物的尿液浓度与传统GN活动指标(红细胞尿、每日蛋白尿(DPU)、反映肾受累的总BVAS评分以及血清肌酐水平和估计肾小球滤过率)之间存在统计学显著相关性(p<0.05)。ROC曲线分析表明,在评估ANCA相关GN的活动度时,尿液MCP-1排泄量≥159 pg/ml具有最高(92%)的敏感性,尿液IV型胶原排泄量≥3.09 μg/l具有最高(86%)的特异性。同时,它们在DPU和ESR联合检测时诊断价值增加(敏感性96%,特异性84.9%)。

结论

MCP-1、KIM-1和IV型胶原的尿液排泄反映了AAV患者局部肾炎症的严重程度,对这些指标的研究是评估ANCA相关GN活动度的一种有前景的诊断工具。

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