2型糖尿病合并经活检证实的糖尿病肾病患者肾小管间质病变、尿N-乙酰-β-D-氨基葡萄糖苷酶及尿β2-微球蛋白的预后价值

Prognostic Value of Tubulointerstitial Lesions, Urinary N-Acetyl-β-d-Glucosaminidase, and Urinary β2-Microglobulin in Patients with Type 2 Diabetes and Biopsy-Proven Diabetic Nephropathy.

作者信息

Mise Koki, Hoshino Junichi, Ueno Toshiharu, Hazue Ryo, Hasegawa Jumpei, Sekine Akinari, Sumida Keiichi, Hiramatsu Rikako, Hasegawa Eiko, Yamanouchi Masayuki, Hayami Noriko, Suwabe Tatsuya, Sawa Naoki, Fujii Takeshi, Hara Shigeko, Ohashi Kenichi, Takaichi Kenmei, Ubara Yoshifumi

机构信息

Nephrology Center, Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan; Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences; and

Nephrology Center.

出版信息

Clin J Am Soc Nephrol. 2016 Apr 7;11(4):593-601. doi: 10.2215/CJN.04980515. Epub 2016 Jan 22.

DOI:10.2215/CJN.04980515

PMID:26801478

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4822660/

Abstract

BACKGROUND AND OBJECTIVES

Some biomarkers of renal tubular injury are reported to be useful for predicting renal prognosis in the early stage of diabetic nephropathy (DN). Our study compared predictions of the renal prognosis by such biomarkers and by histologic tubulointerstitial damage.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Among 210 patients with type 2 diabetes and biopsy-proven DN managed from 1985 to 2011, 149 patients with urinary N-acetyl-β-d-glucosaminidase (NAG) and urinary β2-microglobulin (β2-MG) data at the time of renal biopsy were enrolled. The primary outcome was a decline in eGFR of ≥50% from baseline or commencement of dialysis for ESRD.

RESULTS

The median follow-up period was 2.3 years (interquartile range, 1.1-5.3), and the primary outcome was noted in 94 patients. Mean eGFR was 46.3±23.2 ml/min per 1.73 m(2), and 132 patients (89%) had overt proteinuria at baseline. Cox proportional hazards analysis revealed that the association of urinary NAG and β2-MG with the outcome was attenuated after adjustment for known promoters of progression (+1 SD for log NAG: hazard ratio [HR], 1.14; 95% confidence interval [95% CI], 0.84 to 1.55; +1 SD for log β2-MG: HR, 1.23; 95% CI, 0.94 to 1.62). In contrast, the interstitial fibrosis and tubular atrophy (IFTA) score was still significantly correlated with the outcome after adjustment for the same covariates (+1 for IFTA score: HR, 2.31; 95% CI, 1.56 to 3.43). Moreover, adding the IFTA score to a model containing known progression indicators improved prediction of the outcome (increase of concordance index by 0.02; 95% CI, 0.00 to 0.05; category-free net reclassification improvement by 0.54; 95% CI, 0.03 to 1.05; and relative integrated discrimination improvement by 0.07; 95% CI, -0.08 to 0.22).

CONCLUSIONS

Adding urinary NAG and β2-MG excretion to known promoters of progression did not improve prognostication, whereas adding the IFTA score did. The IFTA score may be superior to these tubulointerstitial markers for predicting the renal prognosis in advanced DN.

摘要

背景与目的

据报道，一些肾小管损伤生物标志物有助于预测糖尿病肾病（DN）早期的肾脏预后。我们的研究比较了此类生物标志物与组织学肾小管间质损伤对肾脏预后的预测情况。

设计、研究地点、参与者及测量指标：在1985年至2011年接受管理的210例2型糖尿病且经活检证实为DN的患者中，纳入了149例在肾活检时具有尿N - 乙酰 - β - d - 氨基葡萄糖苷酶（NAG）和尿β2 - 微球蛋白（β2 - MG）数据的患者。主要结局是估算肾小球滤过率（eGFR）较基线下降≥50%或开始接受终末期肾病（ESRD）透析治疗。

结果

中位随访期为2.3年（四分位间距，1.1 - 5.3），94例患者出现主要结局。平均eGFR为46.3±23.2 ml/（min·1.73 m²），132例患者（89%）在基线时存在显性蛋白尿。Cox比例风险分析显示，在对已知的疾病进展促进因素进行校正后，尿NAG和β2 - MG与结局的关联减弱（log NAG增加1个标准差：风险比[HR]，1.14；95%置信区间[95%CI]，0.84至1.55；log β2 - MG增加1个标准差：HR，1.23；95%CI，0.94至1.62）。相比之下，在对相同协变量进行校正后，间质纤维化和肾小管萎缩（IFTA）评分仍与结局显著相关（IFTA评分为1时：HR，2.31；95%CI，1.56至3.43）。此外，将IFTA评分添加到包含已知疾病进展指标的模型中可改善对结局的预测（一致性指数增加0.02；95%CI，0.00至0.05；无类别净重新分类改善为0.54；95%CI，0.03至1.05；相对综合判别改善为0.07；95%CI， - 0.08至0.22）。