SAT-036 ERYTHROPOIESIS STIMULATING AGENT HYPORESPONSIVENESS AND ITS ASSOCIATION WITH MORTALITY AND HOSPITALISATION

Abstract

In patients with CKD, higher erythropoiesis stimulating agents (ESA) dose might cause higher mortality and increased cardiovascular complications. Hyporesponsiveness to ESA treatment is a known predictor of poor clinical outcomes in haemodialysis (HD) patients. Poor outcomes could be the result of high ESA dosage required in these groups or patient related cause of hypo-responsiveness or a combination of both. We sought to examine whether high erythropoietin resistance index (ERI) was associated with increased all-cause mortality and hospitalisation among incident HD patients. Incident HD patients between January 2010 and December 2016, who completed six months of HD were included in this retrospective observational cohort study. Patients were followed up for one year from the index date (last day of 6 months exposure period) until first of the following – death, withdrawal or end of study (Dec 31, 2017). The main predictor variable was ESA responsiveness measured by ERI (IU/kg/week/g/dl) which was defined as average weekly weight-adjusted EPO dose per average haemoglobin concentration. Patients were divided into 2 groups based on ERI quartiles - ESA hyporesponsive (4th quartile, ERI >15.25+) and ESA responsive group (1st, 2nd and 3rd quartile combined, ERI < 15.25). ESA responsiveness was also assessed by a combination of ESA dosage (high: ≥ median value of ESA dose or low: < median value of ESA dose) and haemoglobin levels (high: ≥ 10 g/dl or low: <10 g/dl). Patients were then divided into 4 groups with low-dose ESA therapy and high haemoglobin (Hb) level as reference category.Primary outcomes were all-cause mortality and hospitalisation during the one year follow-up. Cox regression and Negative binomial regression models were used to determine associations with mortality and hospitalisation among the ERI groups. Binary logistic regression model was used to define the predictors of high ERI. A total of 2302 incident HD patients (mean age 60.1 ± 11.4 years, 56.2% male, 59% Chinese and 69.9% with diabetes as cause of ESRD) were included in the study. During the mean follow-up time of 0.95 ± 0.16 years, 113 (4.9%) patients died. The median EPO dose and mean ERI were 113.9 (IQR, 77.8 to 154.8) IU/kg/week and 12.1± 6.4 IU/kg/week/g/dl respectively. The ESA hyporesponsive group (ERI >15.25+) were more likely to be females, have low albumin, low BMI, low SGA scores and low transferrin saturation % levels but higher KT/V and ferritin levels compared to the ESA responsive group (p<0.001). ESA hyporesponsive group (ERI>15.25+) had 83% higher risk of all-cause mortality (aHR 1.83, 95% CI 1.20 – 2.79, p=0.005) after adjusting for potential confounders. HD patients with high-dose EPO and low Hb levels (ESA hyporesponsive) had significantly higher risk of mortality (aHR 2.42, 95% CI 1.41 – 4.19, p=0.001). The high ERI group also had 36% higher incidence of hospitalisation (IRR 1.36, 95% CI 1.20 – 1.54, p<0.001) compared to low ERI group. The independent predictors of high ERI were female gender, low albumin, high ferritin, low transferrin saturation %, low BMI, high KT/V, high acuity status and increased hospital admissions in the exposure period.View Large Image Figure ViewerDownload Hi-res image Download (PPT) High ERI levels are associated with increased risk of all-cause mortality and hospitalisation in incident HD patients. Lack of data on inflammatory markers is a study limitation.