尿急性肾损伤标志物与抗中性粒细胞胞浆抗体相关性肾炎预后相关性研究

The relationship between the level of urinary biomarker for acute kidney injury and the prognosis of ANCA associated glomerulonephritis

目的分析尿中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase-associated lipocalin,NGAL)及肾脏损伤分子-1(kidney injury molecule-1,KIM-1)与抗中性粒细胞胞浆抗体(anti-neutrophil cytoplasmic antibody,ANCA)相关性肾炎(ANCA associated glomerulonephritis,AAGN)严重程度及预后的关系。方法回顾2009年4月至2013年11月间南京军区南京总医院肾脏科住院的69例AAGN患者,其中抗过氧化物酶抗体阳性61例,抗蛋白酶3抗体阳性8例,肾活检进行病理分型及肾小管间质炎症细胞浸润和肾间质纤维化及肾小管萎缩半定量积分。尿NGAL及KIM-1采用ELISA方法检测,Spearman检验分析尿NGAL及KIM-1与肾脏损害指标(血肌酐、尿蛋白及血白蛋白)的关系,采用Mann-Whitney检验比较组间差异,分析尿NGAL及KIM-1与肾小管病变评分及肾脏预后的关系。结果69例AAV肾脏病理类型:局灶型14例,新月体型26例,混合型29例。基线肌酐:276.69(47.74~1193.40)μmol/L,24 h尿蛋白定量1.61(0.11~9.78)g。3种病理类型之间尿NGAL及KIM-1差异无统计学意义。尿NGAL与尿蛋白及Scr呈正相关(r值分别为0.3242、0.3257,P分别为0.0095、0.0081),与血清白蛋白呈负相关(r=-0.3964,P=0.0009)。尿KIM-1与血清白蛋白呈负相关(r=-0.2539,P=0.0413),但与血肌酐及尿蛋白无相关性。尿KIM-1与肾间质浸润细胞程度相关,差异有统计学意义(P=0.0413)。尿NGAL与肾间质浸润细胞程度无相关性。45例随访24(14~58)个月,13例进入终末期肾脏疾病者基线尿NGAL高于未进入终末期肾脏疾病者[(117.6(3.06~518.4)μg/L对28.86(2.17~461.5)μg/L,P=0.0372)],多因素COX回归分析示尿NGAL为不良肾脏预后的独立危险因素(HR 1.012,95%CI 1.001~1.022,P=0.033)。结论尿NGAL水平反映AAGN的严重程度,为不良肾脏预后的独立危险因素,而KIM-1与间质浸润细胞程度相关。

Objective To analyse the relationship between the level of urine NGAL or KIM- 1 and the severity or prognosis of ANCA associated glomerulonephritis. Methods 69 patients with ANCA associated glomerulonephritis were included, among which 30 patients are males, 39 patients are females, 61 patients are anti-MPO-ANCA positive and 8 patients are anti-PR3 positive. All patients received renal biopsy. The kidney tissues were analysed including the renal histological classification, semi-quantitative score of tubulointerstitial. Urine NGAL and KIM- 1 is tested with ELISA. The relationship between urine NGAL or KIM- 1 and the data including serum creatinine, urinary protein and serum albumin is analyzed by Spearman r test. Parameters between groups were compared using the Mann-Whitney Results Among the 69 patients, 14 patients are focal type, 26 patients are crescentic type and 29 patients are mixed type. Baseline data： serum creatinine is 3.13（0.54-13.5）mg/dL, urinary protein is 1.61（0.11-9.78）g/24h. There are no significant differences for urine NGAL and KIM-1 between different histological types. Urine NGAL is positively correlated with urinary protein and serum creatinine （r=0.3242, 0.3257; P=0.0095, 0.0081）. Urine NGAL is negatively correlated with serum albumin（r=-0.3964, P=0.0009）. Urine KIM-1 is negatively correlated with serum albumin（r=-0.2539, P=0.0413）, but not with serum creatinine and urinary protein. Urine KIM-1 in the high scores group for the interstitial inflammation index is significantly higher than the low scores group（P=0.0413）. Urine NGAL is not significantly correlated with scores for the interstitial inflammation index. Among 45 patients who were followed up for 24（14-58）m, the urine NGAL of the patients who had renal progression is significantly than the urine NGAL of the patients who had no renal progression[ 117.6（3.06-518.4）μ g/L vs 28.86（2.17-461.5） μ g/L, P=0.0372], In a multivariate Cox regression model, Urine NGAL （HR 1.012, 95%CI 1.001-1.022, P=0.033） was independent predictors associated with adverse renal outcome. Conclusion Urine NGAL can reflect the severity of ANCA associated glomerulonephritis and it was independent predictors associated with adverse renal outcome. Urine KIM- 1 is higher in the group who had high scores for the interstitial inflammation index.