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肾损伤分子1(KIM-1):抗中性粒细胞胞浆抗体相关性肾小球肾炎患者急性肾损伤和肾小管间质损伤的潜在生物标志物。

Kidney injury molecule 1 (KIM-1): a potential biomarker of acute kidney injury and tubulointerstitial injury in patients with ANCA-glomerulonephritis.

作者信息

Brilland Benoît, Boud'hors Charlotte, Wacrenier Samuel, Blanchard Simon, Cayon Jérôme, Blanchet Odile, Piccoli Giorgina Barbara, Henry Nicolas, Djema Assia, Coindre Jean-Philippe, Jeannin Pascale, Delneste Yves, Copin Marie-Christine, Augusto Jean-François

机构信息

Service de Néphrologie-Dialyse-Transplantation, Université d'Angers, CHU Angers, Angers, France.

Univ. Angers, Nantes Université, Inserm, CNRS, CRCI2NA, SFR ICAT, Angers, France.

出版信息

Clin Kidney J. 2023 Apr 3;16(9):1521-1533. doi: 10.1093/ckj/sfad071. eCollection 2023 Sep.

Abstract

BACKGROUND

Kidney injury molecule 1 (KIM-1) is a transmembrane glycoprotein expressed by proximal tubular cells, recognized as an early, sensitive and specific urinary biomarker for kidney injury. Blood KIM-1 was recently associated with the severity of acute and chronic kidney damage but its value in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis with glomerulonephritis (ANCA-GN) has not been studied. Thus, we analyzed its expression at ANCA-GN diagnosis and its relationship with clinical presentation, kidney histopathology and early outcomes.

METHODS

We assessed KIM-1 levels and other pro-inflammatory molecules (C-reactive protein, interleukin-6, tumor necrosis factor α, monocyte chemoattractant protein-1 and pentraxin 3) at ANCA-GN diagnosis and after 6 months in patients included in the Maine-Anjou registry, which gathers data patients from four French Nephrology Centers diagnosed since January 2000.

RESULTS

Blood KIM-1 levels were assessed in 54 patients. Levels were elevated at diagnosis and decreased after induction remission therapy. KIM-1 was associated with the severity of renal injury at diagnosis and the need for kidney replacement therapy. In opposition to other pro-inflammatory molecules, KIM-1 correlated with the amount of acute tubular necrosis and interstitial fibrosis/tubular atrophy (IF/TA) on kidney biopsy, but not with interstitial infiltrate or with glomerular involvement. In multivariable analysis, elevated KIM-1 predicted initial estimated glomerular filtration rate (β = -19, 95% CI -31, -7.6,  = .002).

CONCLUSION

KIM-1 appears as a potential biomarker for acute kidney injury and for tubulointerstitial injury in ANCA-GN. Whether KIM-1 is only a surrogate marker or is a key immune player in ANCA-GN pathogenesis remain to be determined.

摘要

背景

肾损伤分子1(KIM-1)是一种由近端肾小管细胞表达的跨膜糖蛋白,被认为是肾脏损伤的早期、敏感且特异的尿液生物标志物。血液中的KIM-1最近与急性和慢性肾损伤的严重程度相关,但其在抗中性粒细胞胞浆抗体(ANCA)相关的肾小球肾炎(ANCA-GN)中的价值尚未得到研究。因此,我们分析了其在ANCA-GN诊断时的表达情况及其与临床表现、肾脏组织病理学和早期预后的关系。

方法

我们评估了缅因-安茹登记处纳入患者在ANCA-GN诊断时及6个月后的KIM-1水平和其他促炎分子(C反应蛋白、白细胞介素-6、肿瘤坏死因子α、单核细胞趋化蛋白-1和五聚素3),该登记处收集了自2000年1月以来在四个法国肾脏病中心诊断的患者数据。

结果

对54例患者进行了血液KIM-1水平评估。诊断时水平升高,诱导缓解治疗后降低。KIM-1与诊断时的肾损伤严重程度及肾脏替代治疗需求相关。与其他促炎分子不同,KIM-1与肾活检时急性肾小管坏死和间质纤维化/肾小管萎缩(IF/TA)的程度相关,但与间质浸润或肾小球受累无关。在多变量分析中,KIM-1升高预测了初始估计肾小球滤过率(β = -19,95%CI -31,-7.6,P =.002)。

结论

KIM-1似乎是ANCA-GN中急性肾损伤和肾小管间质损伤的潜在生物标志物。KIM-1在ANCA-GN发病机制中仅是一个替代标志物还是关键的免疫参与者仍有待确定。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c81/10468750/3fd2fce165fc/sfad071fig1.jpg

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