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原发性肾小球肾炎中尿中性粒细胞明胶酶相关脂质运载蛋白和血清尿酸与间质纤维化及肾小管萎缩的独立关联

Independent associations of urine neutrophil gelatinase-associated lipocalin and serum uric acid with interstitial fibrosis and tubular atrophy in primary glomerulonephritis.

作者信息

Lertrit Amornpan, Worawichawong Suchin, Vanavanan Somlak, Chittamma Anchalee, Muntham Dittapol, Radinahamed Piyanuch, Nampoon Aumporn, Kitiyakara Chagriya

机构信息

Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

出版信息

Int J Nephrol Renovasc Dis. 2016 Apr 20;9:111-8. doi: 10.2147/IJNRD.S103512. eCollection 2016.

Abstract

The degree of interstitial fibrosis and tubular atrophy (IFTA) is one of the strongest prognostic factors in glomerulonephritis (GN). In experimental models, high serum uric acid (UA) could contribute to IFTA through direct effects on the renal tubules, but the significance of this process has not been evaluated in patients. Urine neutrophil gelatinase-associated lipocalin (NGAL) is produced by renal tubules following acute or chronic damage. We investigated the relationship between UA and NGAL excretion in primary GN and tested whether these biomarkers are independently associated with IFTA. Urine and blood were collected from patients on the day of kidney biopsy. IFTA was assessed semi-quantitatively. Fifty-one patients with primary GN were enrolled. NGAL/creatinine correlated significantly with proteinuria but not with glomerular filtration rate (GFR). By contrast, UA correlated with GFR but not with proteinuria. NGAL/creatinine did not correlate with UA. Both NGAL/creatinine and UA increased with the severity of IFTA. By multivariate analysis, GFR, NGAL/creatinine, and UA were independently associated with moderate-to-severe IFTA. Combining UA and NGAL/creatinine with classical predictors (proteinuria and GFR) tended to improve discrimination for moderate-to-severe IFTA. Findings that UA was unrelated to urinary NGAL excretion suggest that the two biomarkers reflect different pathways related to the development of IFTA in primary GN. Both NGAL/creatinine and UA were independently associated with moderate-to-severe IFTA.

摘要

间质纤维化和肾小管萎缩(IFTA)的程度是肾小球肾炎(GN)最强的预后因素之一。在实验模型中,高血清尿酸(UA)可通过对肾小管的直接作用导致IFTA,但这一过程在患者中的意义尚未得到评估。尿液中性粒细胞明胶酶相关脂质运载蛋白(NGAL)是肾小管在急性或慢性损伤后产生的。我们研究了原发性GN中UA与NGAL排泄之间的关系,并测试了这些生物标志物是否与IFTA独立相关。在肾活检当天收集患者的尿液和血液。对IFTA进行半定量评估。纳入了51例原发性GN患者。NGAL/肌酐与蛋白尿显著相关,但与肾小球滤过率(GFR)无关。相比之下,UA与GFR相关,但与蛋白尿无关。NGAL/肌酐与UA不相关。NGAL/肌酐和UA均随IFTA严重程度增加。通过多变量分析,GFR、NGAL/肌酐和UA与中度至重度IFTA独立相关。将UA和NGAL/肌酐与经典预测指标(蛋白尿和GFR)相结合,倾向于改善对中度至重度IFTA的鉴别。UA与尿NGAL排泄无关的发现表明,这两种生物标志物反映了原发性GN中与IFTA发展相关的不同途径。NGAL/肌酐和UA均与中度至重度IFTA独立相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a83/4846074/49876894652a/ijnrd-9-111Fig1.jpg

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