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Urinary Matrix Metalloproteinase 7 and Prediction of IgA Nephropathy Progression.

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.

Authors+Show Affiliations

Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangzhou Regenerative Medicine and Health-Guangdong Laboratory, Guangzhou, China.Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangzhou Regenerative Medicine and Health-Guangdong Laboratory, Guangzhou, China; Division of Nephrology, Affiliated Hospital of Guilin Medical University, Guilin, China.Peking University Institute of Nephrology, Beijing, China.Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangzhou Regenerative Medicine and Health-Guangdong Laboratory, Guangzhou, China.Peking University Institute of Nephrology, Beijing, China.Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangzhou Regenerative Medicine and Health-Guangdong Laboratory, Guangzhou, China; Division of Nephrology, Affiliated Hospital of Guilin Medical University, Guilin, China.Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangzhou Regenerative Medicine and Health-Guangdong Laboratory, Guangzhou, China.Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangzhou Regenerative Medicine and Health-Guangdong Laboratory, Guangzhou, China.Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangzhou Regenerative Medicine and Health-Guangdong Laboratory, Guangzhou, China; Division of Nephrology, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangzhou Regenerative Medicine and Health-Guangdong Laboratory, Guangzhou, China; Division of Nephrology, Guizhou Provincial People's Hospital, Guiyang Medical University, Guiyang, China.Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangzhou Regenerative Medicine and Health-Guangdong Laboratory, Guangzhou, China; Division of Nephrology, Haikou Provincial People's Hospital, Haikou, China.Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangzhou Regenerative Medicine and Health-Guangdong Laboratory, Guangzhou, China.Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangzhou Regenerative Medicine and Health-Guangdong Laboratory, Guangzhou, China.Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangzhou Regenerative Medicine and Health-Guangdong Laboratory, Guangzhou, China. Electronic address: ffhouguangzhou@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31606236

Citation

Yang, Xiaobing, et al. "Urinary Matrix Metalloproteinase 7 and Prediction of IgA Nephropathy Progression." American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, 2019.
Yang X, Ou J, Zhang H, et al. Urinary Matrix Metalloproteinase 7 and Prediction of IgA Nephropathy Progression. Am J Kidney Dis. 2019.
Yang, X., Ou, J., Zhang, H., Xu, X., Zhu, L., Li, Q., ... Hou, F. F. (2019). Urinary Matrix Metalloproteinase 7 and Prediction of IgA Nephropathy Progression. American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, doi:10.1053/j.ajkd.2019.07.018.
Yang X, et al. Urinary Matrix Metalloproteinase 7 and Prediction of IgA Nephropathy Progression. Am J Kidney Dis. 2019 Oct 9; PubMed PMID: 31606236.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Urinary Matrix Metalloproteinase 7 and Prediction of IgA Nephropathy Progression. AU - Yang,Xiaobing, AU - Ou,Jun, AU - Zhang,Hong, AU - Xu,Xin, AU - Zhu,Li, AU - Li,Qingchu, AU - Li,Jiaxin, AU - Xie,Di, AU - Sun,Jingdi, AU - Zha,Yan, AU - Li,Yang, AU - Tian,Jianwei, AU - Liu,Youhua, AU - Hou,Fan Fan, Y1 - 2019/10/09/ PY - 2019/03/14/received PY - 2019/07/18/accepted PY - 2019/10/14/pubmed PY - 2019/10/14/medline PY - 2019/10/14/entrez KW - IgA nephropathy (IgAN) KW - IgAN progression KW - biomarker KW - kidney biopsy KW - matrix metalloproteinase 7 (MMP-7) KW - prognosis KW - risk prediction JF - American journal of kidney diseases : the official journal of the National Kidney Foundation JO - Am. J. Kidney Dis. N2 - 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. SN - 1523-6838 UR - https://www.unboundmedicine.com/medline/citation/31606236/Urinary_Matrix_Metalloproteinase_7_and_Prediction_of_IgA_Nephropathy_Progression L2 - https://linkinghub.elsevier.com/retrieve/pii/S0272-6386(19)30948-5 DB - PRIME DP - Unbound Medicine ER -