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
Service de Néphrologie-Dialyse-Transplantation, Université d'Angers, CHU Angers, Angers, France.
Univ. Angers, Nantes Université, Inserm, CNRS, CRCI2NA, SFR ICAT, Angers, France.
Clin Kidney J. 2023 Apr 3;16(9):1521-1533. doi: 10.1093/ckj/sfad071. eCollection 2023 Sep.
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.
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.
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).
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.
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。
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。
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)。
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。