SUN-291 PREDICTIVE FACTORS OF ESA HYPORESPONSIVENESS IN PRE-DIALYSIS CKD PATIENTS: SECONDARY ANALYSIS OF THE RADIANCE-CKD STUDY

Abstract

Erythropoiesis-Stimulating Agents [ESA] hyporesponsiveness is related to poor renal outcome in management of renal anemia; however, it is difficult to predict which patients will be hyporesponsive. We previously reported on the RADIANCE-CKD study, a multicenter, open-label, randomized controlled study to evaluate renal outcome by different target hemoglobin [Hb] levels using epoetin beta pegol [CERA] in pre-dialysis CKD patients with poor response to ESA (ASN 2018). The aim of the present study was to predict the patients with ESA hyporesponsiveness among pre-dialysis CKD patients. Pre-dialysis CKD patients (362 patients) with poor response to ESA were randomly assigned to an intensive treatment group (I-group; target Hb level of ≥11 g/dl) or a conservative treatment group (C-group; target Hb level of baseline Hb ±1g/dl). The primary renal composite endpoint was a transition to renal replacement therapy, reduction of eGFR to <6 ml/min/1.73 m2, or >30% reduction of eGFR. In the 3-month landmark analysis, the incidence of renal outcome was evaluated in 3 categories of Hb levels (<10, 10 to <11, ≥11 g/dl) according to tertiles of ESA dose. ESA hyporesponsiveness patients (HYPO) were defined as achieved Hb level <11 g/dl with high tertile and achieved Hb level <10 g/dl with mid-tertile in I-group. The predictive factors of hyporesponsiveness patients were then assessed using a logistic regression model and estimated area under the receiver operating characteristic (ROC) curve. Mean age was 74.7 years and 58.6% of patients were male. Mean baseline eGFR in I-group and C-group were 15.3 and 15.9 ml/min/1.73 m2, respectively. Kaplan-Meier analysis and Cox proportional hazards analysis showed no significant difference in the primary end point between the two groups (99 and 109 events) during the 21-month observation period. In the 3-month landmark analysis, achieved Hb level and required ESA dose were higher in I-group. The incidence of the renal composite endpoint had a tendency to increase in accordance with decrease of Hb levels regardless of the ESA dose in both groups. A total of 30 (54.5%) HYPO patients had the renal composite endpoint, as compared with 54 (50.9%) non-HYPO. Based on the logistic regression analysis, 19 background characteristics (age, BW, eGFR, Alb, ferritin, Hb, CRP, etc.) and 14 biomarkers (IL-6, Hepcidin, TGFβ, CD147, PTH, 25Vitamin-D, etc.) were evaluated as predictive factors of HYPO. The obtained area under the ROC curve (AUC) was 0.88, with sensitivity of 84% and specificity of 84%. Using a branch-and-bound algorithm to find the highest likelihood score statistic for 6 variables, the selected variables were age, Hb, Hepcidin, TGFβ, CD147, and PTH; then, the estimated AUC was 0.82. The patients with ESA hyporesponsiveness among Japanese CKD patients can be predicted based on clinical characteristics and biomarkers in pre-dialysis.