Journal Article

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

Roberto Minutolo, Giuseppe Conte, Bruno Cianciaruso, Vincenzo Bellizzi, Andrea Camocardi, Luigi De Paola and Luca De Nicola

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 27, issue 7, pages 2880-2886
Published in print July 2012 | ISSN: 0931-0509
Published online February 2012 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfs007
Hyporesponsiveness to erythropoiesis-stimulating agents and renal survival in non-dialysis CKD patients

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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.

Keywords: Anaemia; CKD; erythropoietin; ESA responsiveness; ESRD

Journal Article.  4392 words.  Illustrated.

Subjects: Nephrology

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