Zhang Yuanyuan, Li Aiju, Wen Jiliang, Zhen Junhui, Hao Qiufa, Zhang Yidan, Hu Zhao, Xiao Xiaoyan
Department of Nephrology, Qilu Hospital of Shandong University, Jinan, China.
Department of Geriatrics, Qilu Hospital of Shandong University, Jinan, China.
Arch Med Res. 2017 Jul;48(5):449-458. doi: 10.1016/j.arcmed.2017.10.005. Epub 2017 Nov 6.
Kidney injury molecule-1 (KIM-1) was identified the most highly upregulated protein in chronic kidney diseases and prolonged KIM-1 expression may be maladaptive. The present study was aimed to investigate urinary, renal and plasma KIM-1 levels and to analyze association between KIM-1 levels with clinical and pathological indexes in adult Henoch-Schönlein purpura (HSP) patients.
Twenty healthy individuals, 20 HSP patients without nephritis and 35 HSP patients with nephritis were recruited. Urinary and plasma KIM-1 levels were determined by ELISA and Luminex, respectively. Renal KIM-1 expression was evaluated by immunohistochemistry.
HSP patients with nephritis were characterized as elevated levels of urinary, renal and plasma KIM-1. Those with more severe tubular injury of renal biopsy tissues presented significantly higher urinary and renal KIM-1 levels compared to control and patients without nephritis. Urinary and renal levels of KIM-1 were positively correlated with blood urea nitrogen and proteinuria, while they were negatively correlated with eGFR at both baseline and after two years follow-up. Moreover, plasma KIM-1 levels were associated with blood urea nitrogen and proteinuria as well. Further univariate correlation analysis indicated urinary and renal KIM-1 levels were positively correlated with interstitial inflammation index and tubulointerstitial chronicity index. Only urinary KIM-1 levels were associated with interstitial inflammation index, tubulointerstitial chronicity index and extracapillary glomerular activity index, after logistic regression analysis. The area under the curve (AUC) for urinary KIM-1/Cr predicting progression of renal damage was significantly greater than the AUC for proteinuria.
This finding suggests that measurement of urinary and renal KIM-1 level may be helpful to evaluate severity of renal pathological damage and prognosis in adult HSP patients with nephritis.
肾损伤分子-1(KIM-1)被确定为慢性肾脏病中上调最为显著的蛋白质,而KIM-1的持续表达可能具有不良适应性。本研究旨在调查成人过敏性紫癜(HSP)患者尿液、肾脏及血浆中KIM-1水平,并分析KIM-1水平与临床及病理指标之间的关联。
招募20名健康个体、20名无肾炎的HSP患者以及35名有肾炎的HSP患者。分别采用酶联免疫吸附测定法(ELISA)和Luminex技术测定尿液和血浆中的KIM-1水平。通过免疫组织化学评估肾脏KIM-1表达。
有肾炎的HSP患者尿液、肾脏及血浆中的KIM-1水平升高。与对照组及无肾炎患者相比,肾活检组织肾小管损伤更严重的患者尿液及肾脏中的KIM-1水平显著更高。在基线期及两年随访后,尿液和肾脏中的KIM-1水平与血尿素氮及蛋白尿呈正相关,而与估算肾小球滤过率(eGFR)呈负相关。此外,血浆KIM-1水平也与血尿素氮及蛋白尿相关。进一步的单变量相关性分析表明,尿液和肾脏中的KIM-1水平与间质炎症指数及肾小管间质慢性化指数呈正相关。经逻辑回归分析后,仅尿液中的KIM-1水平与间质炎症指数、肾小管间质慢性化指数及肾小球球囊外活动指数相关。尿液KIM-1/肌酐比值预测肾损伤进展的曲线下面积(AUC)显著大于蛋白尿的AUC。
这一发现表明,检测尿液及肾脏中的KIM-1水平可能有助于评估成人肾炎性HSP患者肾脏病理损伤的严重程度及预后。