Abstract: Background　Renal interstitial fibrosis（RIF） is a common pathway and the main pathological basis for the development of chronic kidney disease to end-stage renal disease.It is an important factor affecting the prognosis of patients with kidney disease.Early diagnosis and timely treatment are helpful to improve the prognosis.In recent years，many studies have found that RIF can be evaluated by cytokine and other biochemical indices，and ultrasound elastography and other non-invasive tests.However，due to cumbersome operation and high cost，such detections are difficult to be used widely in clinical practice.At present，RIF is manly diagnosed by pathological examination of percutaneous renal biopsy specimens using Masson's trichrome staining or other special staining techniques.But routine pathological diagnosis is made based on the pathologist's electronic microscopic observation of renal interstitial change，which may has subjective error，while diagnosis made using computer aided technology may be an automatic and objective analysis.So we performed a semi-quantitative analysis of microscopic images of the Masson's Trichrome-stained histological sections of RIF.Objective　To assess the diagnostic value of Image-Pro Plus 6.0 in RIF based on this software measured integrated optical density as well as calculated mean optical density （MOD） of Masson's Trichrome-stained histological sections of RIF.Methods　During January to September 2016，from Department of Nephrology，First Affiliated Hospital of Xi'an Jiaotong University，149 cases diagnosed with chronic interstitial nephritis （CIN） and chronic glomerular diseases（RIF group） were enrolled，and by the results of pathological examination of renal biopsy specimens，they were divided into CIN subgroup（including those with a diagnosis of tubulointerstitial nephritis with or without mesangial proliferative glomerulonephritis，n=26） and chronic glomerular disease （CGD） subgroup〔n=123，consisting of IgA nephropathy（n=79）（IgAN Ⅱ-Ⅴby LEE's glomerular grading with 3，35，25，16，respectively）；including IgAN with different degrees of chronic glomerulonephritis hardening（n=44），that is，focal or proliferative sclerosing glomerulonephritis（n=31），or sclerosing glomerulonephritis（n=10），and chronic glomerulonephritis（n=3）〕．They were compared with 27 cases of stageⅠ-Ⅱmembranous nephropathy without RIF confirmed by the same pathological examination in our hospital.Correlations of MOD with clinical indicators 〔serum urea nitrogen （BUN），serum creatinine （Scr），cystatin C，hemoglobin （Hb），and serum and urine β2 microglobulin（β2-MG）〕 were analyzed.ROC analysis of MOD in the diagnosis of RIF was performed，with the optimal cutoff value，sensitivity and specificity were determined.Results　In RIF group，MOD was positively correlated with Scr，serum and urine β2-MG，and was negatively correlated with Hb （P<0.05）.In CGD subgroup，MOD was positively correlated with cystatin C，serum and urine β2-MG，and negatively correlated with Hb （P<0.05）.In the diagnosis of RIF，the AUC of MOD was 0.982〔95%CI（0.961，1.000）〕 when the optimal cutoff value was determined as 0.012 3，with 0.886 sensitivity and 0.963 specificity in RIF group.In CIN subgroup，its AUC was 0.991〔95%CI（0.975，1.000）〕when the optimal cutoff value was determined as 0.011 8，with 1.000 sensitivity and 0.926 specificity.And in CGD subgroup，its AUC was 0.980〔95%CI（0.958，1.000）〕when the optimal cutoff value was determined as 0.008 0，with 0.992 sensitivity and 0.852 specificity.Conclusion　MOD may reflect the degree of RIF，and the estimated optimal cut-off value of diagnosis may be to be 0.012 3.Moreover，it showed high sensitivity and specificity in diagnosing different types of RIF.

Key words: Fibrosis, Renal interstitial fibrosis, Kidney diseases, Diagnosis

摘要： 背景　肾间质纤维化（RIF）是慢性肾脏病（CKD）发展至终末期肾病（ESRD）的主要病理基础，是影响肾脏病患者预后的重要因素。早期明确诊断、及时治疗有助于改善患者预后。近年来，许多研究发现可以通过检测细胞因子等生化指标，以及超声弹性成像技术等无创检测来反映RIF，但因操作烦琐，价格高昂，临床广泛开展还有困难。目前临床主要应用经皮肾组织穿刺活检后进行Masson染色等特殊染色方法来反映RIF，但在常规的病理诊断中，病理医师只能通过在显微镜下的观察来定性描述间质内的改变，存在主观性，而计算机辅助技术可以自动化分析肾间质内的改变，并进行半定量研究。目的　通过Image-Pro Plus 6.0图像分析仪检测Masson染色的肾脏病理切片的积分光密度，计算平均光密度（MOD），探讨其对RIF的诊断价值。方法　收集2016年1—9月于西安交通大学第一附属医院肾内科行肾活检、排除继发性肾脏疾病、诊断为慢性间质性肾炎（CIN）及慢性肾小球疾病（CGD）患者149例作为RIF组，其可分为CIN亚组（包括病理诊断为小管间质性炎，伴或不伴系膜增生性肾小球肾炎患者，n=26）、慢性肾小球疾病（CGD）亚组（n=123）。根据CGD常见类型，分为IgA肾病（IgAN，包括伴有肾小球硬化的IgAN患者，n=79）、慢性肾小球肾炎（n=44）；根据LEE氏标准将IgAN分为IgAN Ⅱ级（n=3）、IgAN Ⅲ级（n=35）、IgAN Ⅳ级（n=25）、IgAN Ⅴ级（n=16），根据慢性肾小球肾炎硬化程度分为局灶硬化性肾小球肾炎（FSGN，n=31）、增生硬化性肾小球肾炎（PSGN，n=10）、硬化性肾小球肾炎（SGN，n=3）。将同期于本院行肾脏穿刺活检明确无RIF的Ⅰ~Ⅱ期膜性肾病患者27例作为对照组。检测研究对象临床指标〔血清尿素氮（BUN）、血清肌酐（Scr）、胱抑素C、血红蛋白（Hb）、血及尿β2微球蛋白（β2-MG）〕。分析各组MOD与临床指标的相关性，绘制MOD诊断各组RIF的受试者工作特征曲线（ROC曲线），计算最佳截断值、灵敏度和特异度。结果　RIF组的MOD与Scr、血及尿β2-MG呈正相关，与Hb呈负相关（P<0.05）。CGD亚组MOD与胱抑素 C、血及尿β2-MG呈正相关，与Hb呈负相关（P<0.05）。MOD诊断RIF的ROC曲线下面积为0.982〔95%CI（0.961，1.000）〕，最佳截断值为0.012 3，灵敏度为0.886，特异度为0.963。MOD诊断CIN亚组RIF的ROC曲线下面积为0.991〔95%CI（0.975，1.000）〕，最佳截断值为0.011 8，灵敏度为1.000，特异度为0.926。MOD诊断CGD亚组RIF的ROC曲线下面积为0.980〔95%CI（0.958，1.000）〕，最佳截断值为0.008 0，灵敏度为0.992，特异度为0.852。结论　Image-Pro Plus 6.0图像分析仪检测Masson染色的肾脏病理切片的MOD可以反映RIF的程度，预测RIF的最佳截断值为0.012 3，诊断不同类型RIF的灵敏度和特异度均较高。

关键词: 纤维化, 肾间质纤维化, 肾疾病, 诊断