Supplementary Material for: Association of Monocyte-Lymphocyte Ratio with Cardiovascular Events and All-Cause Mortality in Patients Undergoing Hemodialysis: A Prospective Cohort Study

Introduction Elevated monocyte to lymphocyte ratio (MLR) represents a pro-inflammatory immune microenvironment and has been associated with poor clinical outcomes such as cardiovascular disease. However, little is known about its association with outcomes among patients on hemodialysis. Methods In a nationwide prospective cohort of 952 patients receiving maintenance hemodialysis from 2011-2013, we examined the association of baseline MLR with subsequent risk of cardiovascular events (cardiovascular-related hospitalization and cardiovascular death) and all-cause mortality, using multivariable Cox proportional hazards models with adjustment for potential confounders. We also examined the mediation effect of inflammatory markers on the association between MLR and cardiovascular events and all-cause mortality, respectively. Results Overall, patients were 60.1±13.4 years old; 53.3% were male; 39.7% were African American; and 56.9% were diabetic. The median dialysis vintage was 3.1 years. During a median follow-up of 2.1 years, 184 and 207 cases experienced cardiovascular events and all-cause death, respectively. A higher MLR was incrementally associated with higher risk of cardiovascular events and all-cause mortality. The multivariable-adjusted hazard ratios (95% confidence interval) of cardiovascular events and all-cause mortality for 0.1 unit increase in MLR were 1.22 (1.09-1.37) and 1.18 (1.07-1.30), respectively. There was a modest but significant mediation effect of plasma interleukin-6 (IL-6) on the association between MLR and cardiovascular events (28.2%) and all-cause mortality (24.1%). Conclusion A higher MLR was independently associated with higher risk of cardiovascular events and all-cause mortality in patients on hemodialysis. Our findings suggest the potential of MLR as a simple, cost-effective prognostic biomarker and support IL-6-targeted therapeutic interventions to improve clinical outcomes in patients with ESKD.