#785 The novel fibrosis biomarker LG1M is prognostic for long-term readmission after AKI

Abstract

Abstract Background and Aims People who survive Acute Kidney Injury (AKI) experience increased risk of long-term adverse outcomes, including a significantly elevated rate of readmission to hospital. This may be related to the pathophysiological consequences of AKI, including extracellular matrix (ECM) remodeling in the kidneys and other organs. Tools to monitor the long-term health risk of patients after AKI are needed to improve patient outcome. Here, we investigated the potential of the novel ECM remodeling biomarker LG1M, reflecting laminin degradation mediated by MMP-9, as a prognostic marker for readmission after AKI. Method We measured LG1M in plasma samples collected 1 year after the episode of AKI using the nordicLG1MTM ELISA assay in plasma samples from 791 patients from the AKI Risk in Derby (ARID) study, who were then followed prospectively until year 3. 390 of the patients had been hospitalized for an episode of AKI and 401 patients who did not sustain AKI were included as controls (non-AKI). Correlation of LG1M levels with age, serum creatinine, eGFR, PCR, ACR, and CRP was tested with Spearman rank correlation (all variables measured at year 1). Uni- and multivariate Cox regression analysis was used to analyze the association of LG1M with the risk of readmission. Results LG1M levels were significantly higher in the AKI group (median [IQR] = 31.9 [25.7-42.8] ng/mL) compared to the control group (median [IQR] = 30.3 [24.9-37.2] ng/mL, P < 0.01). In the AKI group, LG1M correlated with age (r = 0.16, P < 0.01), serum creatinine (r = 0.33, P < 0.0001), eGFR (r = −0.35, P < 0.0001), and ACR (r = 0.23, P < 0.0001). In the control group, LG1M only correlated with serum creatinine (r = 0.22, P < 0.0001) and eGFR (r = −0.22, P < 0.0001). By year 3, 265 out of 390 patients in the AKI group and 258 out of 401 patients in the control group were readmitted (Chi-squared test, P = 0.28). In a univariate Cox model with readmission as outcome, LG1M was significant associated with readmission in the AKI group (HR [95% CI] = 1.007 [1.001-1.013], P < 0.05) but not in the control group (HR [95% CI] = 1.005 [0.997-1.013], P = 0.23). When adjusting for age, sex, ACR, and eGFR measured at year 1 as well as baseline CKD and diabetes status, LG1M lost it significance in the AKI group (HR [95% CI] = 1.004 [0.998-1.011], P = 0.22) and was still non-significant in the control group (HR [95% CI] = 1.002 [0.994-1.011], P = 0.57). Conclusion In this study, we showed that the novel biomarker LG1M is prognostic for readmission in patients after AKI. Our findings may indicate that this biomarker, reflecting laminin degradation, can be used as a novel post-AKI biomarker that can help assess patients’ long-term health risks.