Abstract
BackgroundHyporesponsiveness to erythropoiesis-stimulating agents (ESAs) is associated with cardiovascular events and poor renal outcome in patients with chronic kidney disease (CKD). This study aimed to investigate the initial responsiveness to darbepoetin alfa (DA) and its contributing factors using the data from the BRIGHTEN.MethodsOf 1980 patients enrolled at 168 facilities, 1695 were included in this analysis [285 patients were excluded mainly due to lack of hemoglobin (Hb) values]. The initial ESA response index (iEResI) was defined as a ratio of Hb changes over 12 weeks after DA administration per weight-adjusted total DA dose and contributing factors to iEResI were analyzed.ResultsThe mean age was 70 ± 12 years (male 58.8%; diabetic nephropathy 27.6%). The median creatinine and mean Hb levels at DA initiation were 2.62 mg/dL and 9.8 g/dL, respectively. The most frequent number of DA administration during 12 weeks was 3 times (41.1%), followed by 4 (15.6%) times with a wide distribution of the total DA dose (15–900 μg). Remarkably, 225 patients (13.3%) did not respond to DA. Multivariate analysis showed that male gender, hypoglycemic agent use, iron supplementation, high eGFR, low Hb, low CRP, low NT-proBNP, and low urinary protein–creatinine ratio were independently associated with better initial response to DA (P = < 0.0001, 0.0108, < 0.0001, 0.0476, < 0.0001, 0.0004, 0.0435, and 0.0009, respectively).ConclusionsNon-responder to DA accounted for 13.3% of patients with non-dialysis CKD. Iron supplementation, low CRP, low NT-proBNP, and less proteinuria were predictive and modifiable factors associated with better initial response to DA.
Highlights
Anemia in patients with chronic kidney disease (CKD) is associated with poor renal, cardiovascular, and overall outcomes [1,2,3,4,5]
Some patients showed decreased or no changes in Hb level (ΔHb 0–12 < 0 or = 0) during 12 weeks after darbepoetin alfa (DA) administration; these aforementioned formulae were not used in the data analysis
erythropoiesis-stimulating agents (ESAs) hyporesponsiveness is a strong predictor of mortality and cardiovascular disease (CVD) events as well as poor renal survival in patients with CKD [16, 17, 21,22,23,24,25]
Summary
Anemia in patients with chronic kidney disease (CKD) is associated with poor renal, cardiovascular, and overall outcomes [1,2,3,4,5]. The Correction of Hemoglobin and Outcomes in Renal Insufficiency (CHOIR) trial [14] and the Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT) [15] conducted on pre-dialysis CKD patients showed that targeting higher Hb level compared with targeting lower Hb level increased the. Hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) is associated with cardiovascular events and poor renal outcome in patients with chronic kidney disease (CKD). Multivariate analysis showed that male gender, hypoglycemic agent use, iron supplementation, high eGFR, low Hb, low CRP, low NT-proBNP, and low urinary protein–creatinine ratio were independently associated with better initial response to DA (P = < 0.0001, 0.0108, < 0.0001, 0.0476, < 0.0001, 0.0004, 0.0435, and 0.0009, respectively). Low CRP, low NT-proBNP, and less proteinuria were predictive and modifiable factors associated with better initial response to DA
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