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  • Title: Urinary Matrix Metalloproteinase 7 and Prediction of IgA Nephropathy Progression.
    Author: Yang X, Ou J, Zhang H, Xu X, Zhu L, Li Q, Li J, Xie D, Sun J, Zha Y, Li Y, Tian J, Liu Y, Hou FF.
    Journal: Am J Kidney Dis; 2020 Mar; 75(3):384-393. PubMed ID: 31606236.
    Abstract:
    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 (>3.9μg/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.
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