Abstract
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 follow-up. 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 488-497 |
| Number of pages | 10 |
| Journal | American Journal of Nephrology |
| DOIs | |
| State | Accepted/In press - Dec 14 2017 |
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Keywords
- Anemia
- C-reactive protein End-stage renal disease Type 2 diabetes mellitus
- Chronic kidney disease
- Hemoglobin
ASJC Scopus subject areas
- Nephrology
Cite this
Change in Hemoglobin Trajectory and Darbepoetin Dose Approaching End-Stage Renal Disease : Data from the Trial to Reduce Cardiovascular Events with Aranesp Therapy Trial. / Mc Causland, Finnian R.; Claggett, Brian; Pfeffer, Marc A.; Burdmann, Emmanuel A.; Eckardt, Kai Uwe; Levey, Andrew S.; McMurray, John J.V.; Remuzzi, Giuseppe; Singh, Ajay K.; Solomon, Scott D.; Toto, Robert D.; Parfrey, Patrick.
In: American Journal of Nephrology, 14.12.2017, p. 488-497.Research output: Contribution to journal › Article
}
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
PY - 2017/12/14
Y1 - 2017/12/14
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 follow-up. 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 follow-up. 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
UR - http://www.scopus.com/inward/record.url?scp=85038117726&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85038117726&partnerID=8YFLogxK
U2 - 10.1159/000485326
DO - 10.1159/000485326
M3 - Article
SP - 488
EP - 497
JO - American Journal of Nephrology
JF - American Journal of Nephrology
SN - 0250-8095
ER -