Renalase is a secreted flavoprotein produced by a variety of tissues including the kidneys. A potent growth factor, renalase exerts pro-survival effect by biding to its cell surface receptor PMCA4b and activating various intracellular signaling pathways. In this study, we examined an association between renal function and plasma renalase levels using a new ELISA developed by our group. The unique feature of the ELISA is that its detection monoclonal antibody, m28-renalase, specifically targets the region of human renalase that binds to its cell surface receptor and initiates intracellular signaling. We also examined an association between plasma renalase levels and mortality. 267 patients with different levels of renal function were recruited. The plasma from the blood collected on the day of consent was stored at -80oC until analysis of renalase levels. Total and free renalase levels were measured using the new ELISA. Acidifying plasma samples by adding one volume of 1 N citric acid to two volumes of plasma exposes the binding site for m28-renalase on renalase protein, thus allowing measurement of total renalase proteins. By contrast, with untreated plasma samples, only the renalase proteins with naturally exposed binding sites or free renalase are measured. % free renalase is calculated by dividing free renalase by total renalase and then multiplying by 100. Bivariate analysis was performed for a significant association between covariables (GFR by CKD EPI equation, CKD stages, age, BMI, race, blood pressure, HTN, DM, medications, etc.) and renalase levels (total, free and % free renalase). All significant variables in bivariate analyses were entered in a regression model with the backward elimination. The baseline clinical characteristics of 273 patients were obtained. The range of total renalase was 4.1 to 49.4 µg/ml and that of free renalase 0.13 to 2.6 µg/ml. % free renalase ranged from 1.3 to 6%. In bivariate analysis, total renalase correlated positively with GFR (r = 0.27, p < 0.001) and negatively with CKD stages (ρ = -0.27, p < 0.001). By contrast, % free renalase correlated negatively with GFR (r = - 0.21, p = 0.001) and positively with CKD stages (ρ = 0.24, p < 0.001). No correlation was seen between GFR (or CKD stages) and free renalase. The correlation between renal function and total renalase (and % free renalase) remained statistically significant in the multivariable analysis. After adjusting for age and comorbidities, % free renalase independently predicted death at both 1 year (OR 9.2, 95% CI 1.2-73.6) and 5 years (OR 3.7, 95% CI 1.1-13.3). Free renalase also was an independent predictor of death at 5 years (OR 4.6, CI 1.14-18.5). Using the new ELISA that targets the biologically active site of renalase, we show that loss of GFR is associated with decreasing total renalase levels, a finding opposite from previous studies using commercially available ELISA assays. By contrast, % free renalase increases with loss of GFR. Both % free renalase and free renalase independently predicted mortality. Future studies should focus on understanding the factors that regulate the balance between total and free renalase and how changes in renalase levels affect survival.