TY - JOUR
T1 - Change in hemoglobin trajectory and darbepoetin dose approaching end-stage renal disease
T2 - Data from the trial to reduce cardiovascular events with aranesp therapy trial
AU - Mc Causland, Finnian R.
AU - Claggett, Brian
AU - Pfeffer, Marc A.
AU - Burdmann, Emmanuel A.
AU - Eckardt, Kai Uwe
AU - Levey, Andrew S.
AU - McMurray, John J.V.
AU - Remuzzi, Giuseppe
AU - Singh, Ajay K.
AU - Solomon, Scott D.
AU - Toto, Robert D.
AU - Parfrey, Patrick
N1 - Funding Information:
TREAT was sponsored by Amgen; at that time MAP received grant support from (research grant to Brigham and Women’s Hospital) and served as a consultant to Amgen. No payments in the last 24 months. In addition, MAP has received research support from Novartis and served as a consultant for AstraZeneca, Bayer, Boehringer Ingelheim, DalCor, Genzyme, Gilead, GlaxoSmithKline, Janssen, Lilly, Novartis, Novo Nordisk, Relypsa, Sanofi, Teva, Thra-sos. He holds stock options for DalCor and a patent awarded to Brigham and Women’s Hospital regarding the use of inhibitors of the renin-angiotensin system in MI. Licensed by Novartis, Dr. Pfef-fer’s share irrevocably assigned to charity. FRMC reports consulting fees from GSK. EAB served as a consultant and advisory board member with Baxter, Fresenius and Abbvie. KUE has received honoraria from Akebia, Bayer, Johnson & Johnson, and grant support from Amgen, Astra Zeneca and Vifor. ASL received grant support (research grant to Tufts Medical Center) from Amgen for his efforts in TREAT. AKS reports consulting fees and research support from GSK and Gillead. SDS reports receiving research support and consulting fees from Amgen and consulting for GSK. RDT reports consulting for Amgen, Akebia, Reata, Boehringer-Ingelheim, Bayer, AstraZeneca and NovoNordisk. PP reports lecture honoraria from Amgen. The other authors report no relevant disclosures.
Funding Information:
The TREAT Study was funded by Amgen. This analysis was conducted independently by the authors and they used the data set held at the Brigham and Women’s Hospital; the authors designed and conducted all analyses described herein and were solely responsible for the drafting and editing of this manuscript.
Funding Information:
Dr. Finnian R. Mc Causland is supported by the National Institute of Diabetes and Digestive and Kidney Diseases grant K23DK102511.
Publisher Copyright:
© 2017 S. Karger AG, Basel.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Background: The pathogenesis of chronic kidney disease associated anemia is multifactorial and includes decreased production of erythropoietin (EPO), iron deficiency, inflammation, and EPO resistance. To better understand the trajectory of these parameters, we described temporal trends in hemoglobin (Hb), ferritin, transferrin saturation, C-reactive protein (CRP), and darbepoetin dosing in the Trial to Reduce cardiovascular Events with Aranesp Therapy (TREAT). Methods: We performed a post hoc analysis of 4,038 participants in TREAT. Mixed effects linear regression models were used to determine the trajectory of parameters of interest prior to end-stage renal disease (ESRD). Likelihood ratio tests were used to determine the overall differences in biomarker values and differences in trajectories between those who did and did not develop ESRD. Results: Hb declined precipitously in the year prior to the development of ESRD (irrespective of treatment assignment), and was on average 1.15 g/dL (95% CI -1.26 to -1.04) lower in those who developed ESRD versus those who did not, at the time of ESRD/end of followup. Simultaneously, the mean darbepoetin dose and CRP concentration increased, while serum ferritin and transferrin saturations were >140 μg/L and 20%, respectively. Conclusions: Our analyses provide descriptive insights regarding the temporal changes of Hb, darbepoetin dose, and related parameters as ESRD approaches in participants of TREAT. Hb declined as much as 1-2 years prior to the development of ESRD, without biochemical evidence of iron deficiency. The most precipitous decline occurred in the months immediately prior to ESRD, despite administration of escalating doses of darbepoetin and in parallel with an increase in CRP.
AB - Background: The pathogenesis of chronic kidney disease associated anemia is multifactorial and includes decreased production of erythropoietin (EPO), iron deficiency, inflammation, and EPO resistance. To better understand the trajectory of these parameters, we described temporal trends in hemoglobin (Hb), ferritin, transferrin saturation, C-reactive protein (CRP), and darbepoetin dosing in the Trial to Reduce cardiovascular Events with Aranesp Therapy (TREAT). Methods: We performed a post hoc analysis of 4,038 participants in TREAT. Mixed effects linear regression models were used to determine the trajectory of parameters of interest prior to end-stage renal disease (ESRD). Likelihood ratio tests were used to determine the overall differences in biomarker values and differences in trajectories between those who did and did not develop ESRD. Results: Hb declined precipitously in the year prior to the development of ESRD (irrespective of treatment assignment), and was on average 1.15 g/dL (95% CI -1.26 to -1.04) lower in those who developed ESRD versus those who did not, at the time of ESRD/end of followup. Simultaneously, the mean darbepoetin dose and CRP concentration increased, while serum ferritin and transferrin saturations were >140 μg/L and 20%, respectively. Conclusions: Our analyses provide descriptive insights regarding the temporal changes of Hb, darbepoetin dose, and related parameters as ESRD approaches in participants of TREAT. Hb declined as much as 1-2 years prior to the development of ESRD, without biochemical evidence of iron deficiency. The most precipitous decline occurred in the months immediately prior to ESRD, despite administration of escalating doses of darbepoetin and in parallel with an increase in CRP.
KW - Anemia
KW - C-reactive protein End-stage renal disease Type 2 diabetes mellitus
KW - Chronic kidney disease
KW - Hemoglobin
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U2 - 10.1159/000485326
DO - 10.1159/000485326
M3 - Article
C2 - 29241199
AN - SCOPUS:85038117726
VL - 46
SP - 488
EP - 497
JO - American Journal of Nephrology
JF - American Journal of Nephrology
SN - 0250-8095
IS - 6
ER -