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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 analyze the relationship between urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) and anti-neutrophil cytoplasmic antibody anti-neutrophil cytoplasmic antibody (ANCA) -related glomerulonephritis (AAGN) severity and prognosis. Methods From April 2009 to November 2013, 69 patients with AAGN who were hospitalized in Department of Nephrology, Nanjing General Hospital of Nanjing Military Region were investigated. Anti-peroxidase antibody was positive in 61 cases and anti-protease 3 antibody was positive in 8 cases. Type and tubulointerstitial inflammatory cell infiltration and renal interstitial fibrosis and tubular atrophy semi-quantitative integration. The urinary NGAL and KIM-1 were detected by ELISA. Spearman test was used to analyze the relationship between urine NGAL and KIM-1 and renal damage indexes (serum creatinine, urine protein and serum albumin). Mann-Whitney test was used to compare the differences between groups. Relationship between NGAL, KIM-1 and renal tubular score and renal prognosis. Results 69 cases of AAV kidney pathological type: foci in 14 cases, 26 cases of crescent size, mixed type in 29 cases. Baseline creatinine: 276.69 (47.74 ~ 1193.40) μmol / L, 24 h urinary protein quantitative 1.61 (0.11 ~ 9.78) g. There was no significant difference in urinary NGAL and KIM-1 between the three pathological types. Urinary NGAL was positively correlated with urinary protein and Scr (r = 0.3242,0.3257, P = 0.0095,0.0081, respectively), but negatively correlated with serum albumin (r = -0.3964, P = 0.0009). Urinary KIM-1 was negatively correlated with serum albumin (r = -0.2539, P = 0.0413), but not with serum creatinine and urine protein. Urinary KIM-1 was associated with the degree of interstitial infiltration of cells, the difference was statistically significant (P = 0.0413). There was no correlation between urinary NGAL and renal interstitial infiltration. 45 cases were followed up for 24 months (14-58 months). The baseline urinary NGAL of 13 patients who entered end-stage renal disease was higher than those who did not enter end-stage renal disease (117.6 (3.06-518.4) μg / L vs. 28.86 (2.17-461.5) μg / L, P = 0.0372). Multivariate Cox regression analysis showed that urinary NGAL was an independent risk factor for adverse renal outcomes (HR 1.012, 95% CI 1.001-1.0222, P = 0.033). Conclusion The level of urinary NGAL reflects the severity of AAGN and is an independent risk factor for adverse renal prognosis. KIM-1 is correlated with the degree of interstitial infiltration.