P0855ASSOCIATIONS BETWEEN A COMPREHENSIVE PANEL OF BIOMARKERS WITH ESA HYPORESPONSIVENESS: ROLE OF IMMUNE DYSFUNCTION IN THE PATHOPHYSIOLOGY OF CKD ANEMIA

Abstract Background and Aims An inadequate response to the treatment of anemia with erythropoiesis-stimulating agents (ESAs) in patients with chronic kidney disease is a challenging and common clinical condition previously associated with signs of inflammation and episodic clinical events. The associations between different immune response pathways and ESA hyporesponsiveness remain poorly understood. Here we describe the associations between a comprehensive panel of inflammatory biomarkers and ESA resistance in a group of stable HD patients. Method This is post-hoc analysis of the baseline evaluation of patients enrolled in the HDFIT, a randomized controlled trial. A panel comprising a more general (CRP), innate (IL-1β and IL-6), adaptive (IFNγ, IFNα2) biomarkers of immune response, and also a specific vascular inflammation (MCP-1) biomarkers were simultaneously measured with the same serum sample through turbidimetry and Milliplex Human Cytokine Magnetic Bead Panel - EMD Milipore Corporation, USA. Multivariable analysis was used to assess the association of their concentrations with the erythropoietin resistance index (ERI), defined as the weekly ESA dose divided by hemoglobin level. Results A total of 155 patients were included in this analysis (mean age 52 ± 6; 70% male; 32% with diabetes; mean hemoglobin 11.7 ± 1.5; median ESA dose/week 8000 IU IQR: 4000-12.000). Patients in the highest ERI tercile were mostly female, younger, more diabetic and with slightly higher proportion of iron prescription compared to those in the lowest tercile of ERI. The multivariable models adjusted for age, sex, diabetes and vascular access demonstrated that higher serum levels of IL-1β and IFN-γ were associated with higher ESA resistance, while there were no detectable associations of serum levels of IL-6 or CRP and ERI. Conclusion Among the biomarkers included in this comprehensive panel of biomarkers representing the multilevel nature of immune dysfunction in CKD, we observed associations between higher concentrations of innate (IL-1β) and adaptive (IFN) immune response and ESA hyporesponsiveness. Our results support the role of immune dysfunction in the pathophysiology of CKD anemia. Figure 1: Estimates of linear coefficients of log-transformed concentrations of biomarkers on log-transformed ERI, adjusted for age, sex, diabetes, vascular access.