Renal Division, Department of Medicine, Peking University First Hospital; Institute of Nephrology, Peking University; Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, People's Republic of China.
Renal Pathology Room, Peking University First Hospital, Beijing, People's Republic of China.
Am J Physiol Renal Physiol. 2019 Sep 1;317(3):F584-F592. doi: 10.1152/ajprenal.00176.2019. Epub 2019 Jul 10.
Acute tubulointerstitial nephritis (ATIN) is a common cause of acute kidney injury characterized by inflammatory cells infiltrating in the interstitium. The present study aimed to explore noninvasive biomarkers that might indicate activity of pathological injuries and help direct treatment. Fifty-four patients with clinical-pathologically diagnosed ATIN from January 1, 2014, to June 30, 2016, at Peking University First Hospital were enrolled. Urine samples were collected on the morning of renal biopsy and assessed for urinary kidney injury molecule-1 (KIM-1) and urinary soluble C5b-9 (sC5b-9). Immunofluorescence staining for KIM-1 and C5b-9 was performed in biopsied kidney sections from ATIN cases. The clinical and pathological relevance of the two urinary biomarkers was analyzed. Both urinary KIM-1 and sC5b-9 values were significantly elevated in patients with ATIN compared with healthy controls. The urinary KIM-1 level positively correlated with urinary -acetyl-β-d-glucosaminidase ( = 0. 542, = 0.001) and the pathological tubular injury score ( = 0.469, < 0.001), whereas the urinary sC5b-9 level was related to pathological activity scores for tubular injury ( = 0.413, = 0.002), interstitial inflammation ( = 0.388, = 0.004), and treatment response ( = 0.564, < 0.001). Urinary KIM-1 tended to have better diagnostic value for tubular injury than urinary sC5b-9, whereas only urinary sC5b-9 was able to demonstrate severe interstitial inflammation. A combination of urinary KIM-1 and sC5b-9 had an area under the receiver-operating characteristic curve of 0.864 (95% confidence interval: 0.766-0.963, < 0.001, sensitivity: 75%, specificity: 88%) for acute tissue injury in ATIN. KIM-1 expression was markedly increased in renal tubular cells in both ATIN and acute tubular necrosis conditions, whereas a significant upregulation of C5b-9 was only detected in the tubular cells and interstitial cells in ATIN cases. Urinary KIM-1 is a specific biomarker for renal tubular injury in ATIN, whereas urinary sC5b-9 is valuable in demonstrating severe interstitial inflammation. The combination of these two biomarkers helps identify patients at an acute injury stage and, therefore, might facilitate clinical evaluation and guide immunosuppressive therapy.
急性肾小管间质性肾炎（ATIN）是一种常见的急性肾损伤，其特征为炎症细胞浸润间质。本研究旨在探讨可能提示病理损伤活动并有助于指导治疗的非侵入性生物标志物。
2014 年 1 月 1 日至 2016 年 6 月 30 日，北京大学第一医院临床病理诊断为 ATIN 的 54 例患者纳入本研究。在肾活检当天早上收集尿液样本，评估尿肾损伤分子 1（KIM-1）和尿可溶性 C5b-9（sC5b-9）。对 ATIN 患者活检肾组织进行 KIM-1 和 C5b-9 的免疫荧光染色。分析这两种尿生物标志物的临床和病理相关性。
与健康对照组相比，ATIN 患者的尿 KIM-1 和 sC5b-9 值均显著升高。尿 KIM-1 水平与尿 -乙酰-β-d-氨基葡萄糖苷酶（r=0.542，P=0.001）和肾小管损伤病理评分（r=0.469，P<0.001）呈正相关，而尿 sC5b-9 水平与肾小管损伤病理活动评分（r=0.413，P=0.002）、间质炎症（r=0.388，P=0.004）和治疗反应（r=0.564，P<0.001）相关。尿 KIM-1 对肾小管损伤的诊断价值优于尿 sC5b-9，而只有尿 sC5b-9 能够显示严重的间质炎症。尿 KIM-1 和 sC5b-9 联合检测的受试者工作特征曲线下面积为 0.864（95%置信区间：0.766-0.963，P<0.001，敏感性：75%，特异性：88%），可用于评估 ATIN 的急性组织损伤。在 ATIN 和急性肾小管坏死的情况下，KIM-1 表达均明显增加，但只有在 ATIN 病例中，肾小管细胞和间质细胞中才明显上调 C5b-9。尿 KIM-1 是 ATIN 肾小管损伤的特异性生物标志物，而尿 sC5b-9 则有助于显示严重的间质炎症。这两种生物标志物的联合应用有助于识别处于急性损伤阶段的患者，从而可能有助于临床评估和指导免疫抑制治疗。
