Matrix Metalloproteinase-2 and CKD Progression: The Chronic Renal Insufficiency Cohort (CRIC) Study

• Published in: Kidney medicine 2024-08, Vol.6 (8), p.100850, Article 100850
• Main Authors: Baudier, Robin L., Orlandi, Paula F., Yang, Wei, Chen, Hsiang-Yu, Bansal, Nisha, Blackston, J. Walker, Chen, Jing, Deo, Rajat, Dobre, Mirela, He, Hua, He, Jiang, Ricardo, Ana C., Shafi, Tariq, Srivastava, Anand, Xie, Dawei, Susztak, Katalin, Feldman, Harold I., Anderson, Amanda H., Appel, Lawrence J., Cohen, Debbie, Dember, Laura, Go, Alan S., Lash, James P., Nelson, Robert G., Rahman, Mahboob, Rao, Panduranga S., Shah, Vallabh O., Unruh, Mark L.
• Format: Article
• Language: English
• Subjects: chronic kidney disease (CKD); CKD progression; eGFR slope; fibrosis; initiation of kidney replacement therapy (KRT); Matrix metalloproteinase 2 (MMP-2)
• ISSN: 2590-0595; 2590-0595
• DOI: 10.1016/j.xkme.2024.100850

Matrix metalloproteinase 2 (MMP-2) plays an important role in the development of fibrosis, the final common pathway of chronic kidney disease (CKD). This study aimed to assess the relationship between repeated measures of MMP-2 and CKD progression in a large, diverse prospective cohort. In a prospective cohort of Chronic Renal Insufficiency Cohort (CRIC) participants (N=3,827), MMP-2 was measured at baseline. In a case-cohort design, MMP-2 was additionally measured at year 2 in a randomly selected subcohort and cases of estimated glomerular filtration rate (eGFR) halving or kidney replacement therapy (KRT) (N = 1,439). CRIC is a multicenter prospective cohort of adults with CKD. MMP-2 measured in plasma at baseline and at year 2. A composite kidney endpoint (KRT/eGFR halving) Weighted Cox proportional hazards models for case-cohort participants. Participants were followed for a median of 4.6 years from year 2 and 6.9 years from the baseline. Persistently elevated MMP-2 (≥300ng/mL at both baseline and year 2) increased the hazard of the composite kidney endpoint (HR, 1.61; 95% CI, 1.07-2.42; P=0.09) after adjusting for covariates. The relationship of persistently elevated MMP-2 was modified by levels of inflammation, with a 2.6 times higher rate of the composite kidney endpoint in those with high-sensitivity C-reactive protein