A novel biomarker of laminin turnover is associated with disease progression and mortality in chronic kidney disease

BackgroundPatients with chronic kidney disease (CKD) have increased risk of development of end-stage renal disease (ESRD) and early mortality. Fibrosis is the central pathogenic process in CKD and is caused by dysregulated extracellular matrix (ECM) remodeling. The laminin γ1 chain (LAMC1) is a core structural protein present in the basement membrane of several organs, including the kidneys. We hypothesized that dysregulation of LAMC1 remodeling could be associated with a higher risk of adverse clinical outcomes in patients with CKD.MethodsA novel immunoassay targeting LG1M, a specific MMP-9-generated neo-epitope fragment of LAMC1, was developed and used to measure the levels of the fragment in urine and serum from 492 patients from the Renal Impairment in Secondary Care (RIISC) study, a prospective cohort of patients with high-risk CKD. Patients were monitored for a median follow-up time of 3.5 years. Associations between serum and urine LG1M levels and progression of CKD at 12 months were assessed by a multivariable logistic regression model. The association with ESRD or mortality was assessed by Kaplan-Meier survival curves and Cox proportional hazards regression.ResultsForty-six (11%) of the 416 patients who reached 12-month follow-up had progression of CKD; during the study follow-up, 125 patients (25.4%) developed ESRD and 71 patients (14.4%) died. Serum and urine levels of LG1M correlated with baseline eGFR (r = -0.43, pConclusionsLG1M, a marker of basement membrane remodeling, is increased in serum and urine of patients with CKD and levels are associated with one-year disease progression, development of ESRD, and mortality.