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


CONCLUSIONS
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.
Division of Nephrology, Second University of Naples, Naples, Italy. roberto.minutolo@unina2.it
Roberto
R
Minutolo
Giuseppe
G
Conte
Bruno
B
Cianciaruso
Vincenzo
V
Bellizzi
Andrea
A
Camocardi
Luigi
L
De Paola
Luca
L
De Nicola
D000368:Aged; D002318:Cardiovascular Diseases / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D048909:Diabetes Complications / Q000139:chemically induced / Q000401:mortality; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000401:mortality; D004920:Erythropoiesis / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D006397:Hematinics / Q000009:adverse effects*; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007676:Kidney Failure, Chronic / Q000139:chemically induced* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D006435:Renal Dialysis; D015996:Survival Rate
D006397:Hematinics; D006454:Hemoglobins