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. 2017 Oct;8(10):305-318.
doi: 10.1177/2042098617716819. Epub 2017 Jul 12.

A threshold trajectory was revealed by isolating the effects of hemoglobin rate of rise in anemia of chronic kidney disease

Gregory Fusco  1 , Ali Hariri  2 , Carlos Vallarino  3 , Ajay Singh  4 , Peter Yu  3 , Lesley Wise  5
Affiliations

A threshold trajectory was revealed by isolating the effects of hemoglobin rate of rise in anemia of chronic kidney disease

Gregory Fusco et al. Ther Adv Drug Saf. 2017 Oct.

Abstract

Background: To assess cardiovascular risk among various hemoglobin (Hb) rates of rise (RoR) in chronic kidney disease (CKD) patients with anemia who have initiated therapy with erythropoiesis stimulating agents (ESAs).

Methods: Observational cohort of CKD patients initiating ESA therapy from the Centricity® database, 1990-2011. Proportional hazards models tested the hypothesis that a slower Hb RoR (0 < g/dl/month ⩽ 0.125) is associated with a lower cardiovascular (CV) incidence [composite of fatal/nonfatal myocardial infarction (MI) and stroke] compared with faster RoR (0.125 < g/dl/month ⩽ 2.0, and >2.0 g/dl/month).

Results: A total of 9220 patients receiving ESAs were followed for an average of 3.1 years. Slow (group B) RoR versus medium (group C') and fast (group D') RoR in Hb, throughout all Hb milestones, was associated with lower risk of the composite endpoint [B (slow) versus D' (fast) [hazard ratio (HR) = 0.20 (0.11, 0.39), p < 0.0001]; B versus C' (medium) [HR = 0.34 (0.19, 0.62), p = 0.0004], and C' versus D' [HR = 0.60 (0.42, 0.85), p = 0.005]]. Within achieved Hb milestones, HRs were: B versus D' at milestone ⩾ 14.1 g/dl [HR = 0.17 (0.05, 0.56); p = 0.004] and at milestone 12.6-14.0 [HR = 0.18 (0.07, 0.46), p = 0.0004].

Conclusion: Rapid Hb rise is associated with adverse CV outcomes, with markedly lower risk for rates below a threshold trajectory of 0.125 g/dl/month, even with complete correction.

Keywords: chronic kidney disease anemia; erythropoiesis stimulating agents; hemoglobin rate of rise; hemoglobin reconstitution; hyporesponsiveness; management of; threshold trajectory.

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Conflict of interest statement

Conflict of interest statement: During the development of this study, GF has been employed by Epividian, Inc. and Takeda Pharmaceuticals International, AH has been employed by Sanofi Pharmaceuticals, Ionis Pharmaceuticals and Takeda Pharmaceuticals International, CV has been employed by Takeda Pharmaceuticals International, AS has been employed by Brigham and Women’s Hospital, PY has been employed by Takeda Pharmaceuticals International, LW has been employed by Wise Pharmacovigilance and Risk Management and Takeda Pharmaceuticals International. AS has served as a consultant for Sandoz, HIS Dialysis, Rockwell, Amgen, Roche, FibroGen, Keryx and Takeda and has received grant support from Johnson & Johnson, Concert, Genentech and Genzyme. AS and GF have executed a confidentiality agreement with Takeda for this study, and none of the authors have either requested or received compensation, outside of previous employment, for his or her contribution to this study.

Figures

Figure 1.
Figure 1.
Study population. Dx, diagnosis; Rx, treatment; CKD, chronic kidney disease; ESA, erythropoiesis stimulating agent; CV, cardiovascular; Hb, hemoglobin.
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