Urinary Matrix Metalloproteinase 7 and Prediction of IgA Nephropathy Progression
Urinary Matrix Metalloproteinase 7 and Prediction of IgA Nephropathy Progression
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DOI：
10.1053/j.ajkd.2019.07.018
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发表时间：
2020-03-01
影响因子：
13.2
通讯作者：
Hou, Fan Fan
中科院分区：
文献类型：
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作者：
Yang, Xiaobing;Ou, Jun;Hou, Fan Fan
理由和目标：免疫球蛋白A肾病（IgAN）管理的一个主要挑战是无法在早期阶段识别疾病进展的高风险患者。我们的目的是确定尿基质金属蛋白酶7（MMP-7）是否是IgAN进展的一个有希望的预测因子，以及在活检时将其加入临床数据是否可以提高风险预测。作为训练集，在1个临床中心对946例IgAN中国患者进行了中位40个月的随访（n = 554）在第二个临床中心作为验证集（n = 392）进行28个月的研究。预测因素：在肾活检时测量的尿MMP-7和7种先前报道的生物标志物以及组织学定义的疾病严重程度评分（MEST-C）。IgAN进展定义为肾小球滤过率损失>40%、肾功能衰竭或死亡的复合物。分析方法：考克斯比例风险模型校正了临床特征、肾功能、相关药物和MEST-C评分。在3年时计算IgAN进展的风险分类统计，包括C统计，净重新分类指数和综合判别指数。结果：在校正分析中，高水平（> 3.9 μ g/g肌酐）的尿MMP-7与IgAN进展的2.7倍高风险相关。在预测IgAN进展方面，尿MMP-7水平优于尿血管紧张素原（C统计值，0.75）、表皮生长因子（C统计值，0.75）、肾损伤分子1（C统计值，0.68）和血清半乳糖缺陷型IgA 1（C统计值，0.59）。将尿MMP-7水平添加到具有活检时的临床数据的模型中（估计肾小球滤过率、平均动脉血压和蛋白尿）和MEST-C评分显著改善了C统计量，从0.79提高到0.85，改善了IgAN进展的3年风险预测。（从0.84到0.90的C统计），并改善了风险重新分类（无类别净重新分类改善，0.60）。尿MMP-7水平的预测性能，单独或结合临床数据，是一致的外部validationset.Limitations：缺乏验证在其他种族population.Conclusions：在这项研究队列，尿MMP-7水平是一个独立的预测IgA肾病进展。在MEST-C评分和活检时的临床数据中加入尿MMP-7水平显著提高了IgAN进展的风险预测。
Rationale & Objective: A major challenge in the management of immunoglobulin A nephropathy (IgAN) is the inability to identify patients at high risk for disease progression at an early stage. Our objective was to determine whether urinary matrix metalloproteinase 7 (MMP-7) is a promising predictor for IgAN progression and whether its addition to clinical data at the time of biopsy improves risk prediction.Study Design: Prospective observational cohort study in China.Setting & Participants: 946 Chinese patients with IgAN followed up for a median of 40 months in 1 clinical center serving as the training set (n = 554) and for 28 months in a second clinical center serving as the validation set (n = 392).Predictors: Urinary MMP-7 and 7 previously reported biomarkers measured at the time of kidney biopsy and a score of histologically defined disease severity (MEST-C).Outcomes: IgAN progression was defined as a composite of >40% loss of estimated glomerular filtration rate, kidney failure, or death.Analytical Approach: Cox proportional hazard models adjusted for clinical characteristics, kidney function, relevant medications, and MEST-C score. Risk classification statistics were calculated for IgAN progression at 3 years, including C statistic, net reclassification index, and integrated discrimination index.Results: High levels (> 3.9 mu g/g of creatinine) of urinary MMP-7 were associated with a 2.7-fold higher risk for IgAN progression in adjusted analyses. Urinary MMP-7 level outperformed (C statistic, 0.78) levels of urinary angiotensinogen (C statistic, 0.75), epidermal growth factor (C statistic, 0.75), kidney injury molecule 1 (C statistic, 0.68), and serum galactose-deficient IgA1 (C statistic, 0.59) for predicting IgAN progression. The addition of urinary MMP-7 level to a model with clinical data from the time of biopsy (estimated glomerular filtration rate, mean arterial blood pressure, and proteinuria) and MEST-C score significantly improved the C statistic from 0.79 to 0.85, improved the 3-year risk prediction of IgAN progression (from 0.84 to C statistic of 0.90), and improved risk reclassification (category-free net reclassification improvement, 0.60). The predictive performance of urinary MMP-7 level, alone or combined with clinical data, was consistent in the external validation set.Limitations: Lack of validation in other ethnic populations.Conclusions: In this study cohort, urinary MMP-7 level is an independent predictor of IgAN progression. The addition of urinary MMP-7 level to MEST-C score and clinical data at the time of biopsy significantly improved risk prediction of IgAN progression.