C-reactive protein but not hepcidin, NGAL and transferrin determines the ESA resistance in hemodialysis patients

Background: Erythropoiesis-stimulating agents (ESA) are commonly used for the treatment of anemia in hemodialysis (HD) patients, however, 5-10% of these patients have resistance to ESA treatment. Hepcidin and neutrophil-gelatinase associated lipocalin (NGAL) are induced by inflammation and these proteins may take role in ESA resistance. Herein, we aimed to investigate the effects of serum hepcidin, NGAL, transferrin and C-reactive protein (CRP) levels on ESA resistance in HD patients. Methods: A total of 63 chronic HD patients (6.0 +/- 17years, M/F:44/19) and 20 healthy controls (6.0 +/- 4years, M/F:14/6) were enrolled. ESA resistance index (ERI) was calculated as weekly ESA dose (IU)/body weight (kg)/hemoglobin level (g/dL). Patients on ESA treatment were divided into two groups depending on the median ERI value as low and high ERI groups. Results: Serum ferritin, hepcidin and NGAL levels were significantly higher in HD patients compared with controls. Serum transferrin levels were lower in high ESA index group compared with patients without ESA treatment and healthy controls. ERI was significantly correlated with serum CRP levels (r=0.55, p<0.001). In HD patients, serum hepcidin levels were associated with ferritin (r=0.55, p<0.01) and creatinine (r=0.27, p=0.03). Dose of ESA was significantly associated with serum CRP (r=0.34, p=0.02), total protein (r=-0.34, p=0.01), transferrin (r=-0.28, p=0.04) and ferritin (r=0.31, p=0.02). In linear regression analysis to predict ERI, age, gender, serum CRP, hepcidin, NGAL, albumin, ferritin and BMI were included (Model R=0.62, R-2=0.38, p=0.02). Serum CRP was the only significant factor predicting ERI. Conclusion: CRP was the only predictor of ESA resistance index in HD patients. Hepcidin, NGAL and transferrin were not found to be markers of ESA resistance.