Change in Hemoglobin Trajectory and Darbepoetin Dose Approaching End-Stage Renal Disease

Data from the Trial to Reduce Cardiovascular Events with Aranesp Therapy Trial

Finnian R. Mc Causland, Brian Claggett, Marc A. Pfeffer, Emmanuel A. Burdmann, Kai Uwe Eckardt, Andrew S. Levey, John J.V. McMurray, Giuseppe Remuzzi, Ajay K. Singh, Scott D. Solomon, Robert D. Toto, Patrick Parfrey

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 languageEnglish (US)
Pages (from-to)488-497
Number of pages10
JournalAmerican Journal of Nephrology
DOIs
StateAccepted/In press - Dec 14 2017

Fingerprint

Chronic Kidney Failure
Hemoglobins
C-Reactive Protein
Therapeutics
Transferrin
Ferritins
Erythropoietin
Linear Models
Iron
Darbepoetin alfa
Chronic Renal Insufficiency
Anemia
Biomarkers
Inflammation
Serum

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 journalArticle

Mc Causland, FR, Claggett, B, Pfeffer, MA, Burdmann, EA, Eckardt, KU, Levey, AS, McMurray, JJV, Remuzzi, G, Singh, AK, Solomon, SD, Toto, RD & Parfrey, P 2017, 'Change in Hemoglobin Trajectory and Darbepoetin Dose Approaching End-Stage Renal Disease: Data from the Trial to Reduce Cardiovascular Events with Aranesp Therapy Trial', American Journal of Nephrology, pp. 488-497. https://doi.org/10.1159/000485326
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. / Change in Hemoglobin Trajectory and Darbepoetin Dose Approaching End-Stage Renal Disease : Data from the Trial to Reduce Cardiovascular Events with Aranesp Therapy Trial. In: American Journal of Nephrology. 2017 ; pp. 488-497.
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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.",
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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

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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.

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