Hyporesponsiveness to erythropoiesis-stimulating agents and renal survival in non-dialysis CKD patients

Abstract

Background: Lower responsiveness to erythropoiesis-stimulating agents (ESA-R) predicts cardiovascular (CV) events. Whether ESA-R also affects the risk of end-stage renal disease (ESRD) is unknown.

Methods: We evaluated ESA-R in 194 consecutive chronic kidney disease (CKD) patients, regularly seen in outpatient nephrology clinics, who started erythropoiesis-stimulating agent (ESA) therapy between 2002-06. Exclusion criteria were causes of anaemia other than CKD or recent transfusion. ESA-R was calculated as (Hb1-Hb0)/time/ESA dose (g/dL/month/10 μg/week of ESA). Patients were classified, from lower to higher tertile of ESA-R, as poor, intermediate and good responders. Time to ESRD was the primary outcome.

Results: Age was 64±16 years, 48% were male, 34% had diabetes and 32% had CV disease, glomerular filtration rate (GFR) 24±13 mL/min/1.73 m2 and proteinuria 0.6 g/dL (interquartile range 0.2-1.9). First ESA dose was 23.7±10.8 μg/week; haemoglobin (Hb) increased from 9.9±0.8 g/dL to 11.0±1.2 g/dL at first control, obtained after 1.4±0.4 months. These changes corresponded to an ESA-R of 0.37±0.38 g/dL/month/10 μg/week of ESA and tertiles limits were 0.17 and 0.47. Poor responders were younger and had lower GFR and higher proteinuria than intermediate and good responders. During the first 6 months of ESA therapy, poor responders showed lower Hb levels and sustained longer periods of Hb level<11 g/dL. During follow-up (median 3.0 years), 99 patients reached ESRD. At multivariable Cox's analysis, poor responsiveness was associated with higher risk of ESRD (hazard ratio 2.49, 95% confidence interval 1.28-4.84).

Conclusion: ESA-R predicts renal prognosis in CKD patients followed in nephrology practice, where ESRD is the predominant outcome and ESA is commonly used at low dose.