Effect of hemoglobin target on progression of kidney disease: a secondary analysis of the CHOIR (Correction of Hemoglobin and Outcomes in Renal Insufficiency) trial

Abstract

Background: Conflicting relationships have been described between anemia correction using erythropoiesis-stimulating agents and progression of chronic kidney disease (CKD). This study was undertaken to examine the impact of target hemoglobin level on progression of kidney disease in the CHOIR (Correction of Hemoglobin and Outcomes in Renal Insufficiency) trial.

Study design: Secondary analysis of a randomized controlled trial.

Setting & participants: 1,432 participants with CKD and anemia.

Intervention: Participants were randomly assigned to target hemoglobin levels of 13.5 versus 11.3 g/dL with the use of epoetin alfa.

Outcomes & measurements: Cox regression was used to estimate HRs for progression of CKD (a composite of doubling of creatinine level, initiation of renal replacement therapy, or death). Interactions between hemoglobin target and select baseline variables (estimated glomerular filtration rate, proteinuria, diabetes, heart failure, and smoking history) also were examined.

Results: Participants randomly assigned to higher hemoglobin targets experienced shorter time to progression of kidney disease in both univariate (HR, 1.25; 95% CI, 1.03-1.52; P = 0.02) and multivariable models (HR, 1.22; 95% CI, 1.00-1.48; P = 0.05). These differences were attributable to higher rates of renal replacement therapy and death for participants in the high hemoglobin arm. Hemoglobin target did not interact with estimated glomerular filtration rate, proteinuria, diabetes, or heart failure (P > 0.05 for all). In the multivariable model, hemoglobin target interacted with tobacco use (P = 0.04) such that the higher target had a greater risk of CKD progression for participants who currently smoked (HR, 2.50; 95% CI, 1.23-5.09; P = 0.01), which was not present for those who did not currently smoke (HR, 1.15; 95% CI, 0.93-1.41; P = 0.2).

Limitations: A post hoc analysis; thus, cause and effect cannot be determined.

Conclusions: These results suggest that a high hemoglobin target is associated with a greater risk of progression of CKD. This risk may be augmented by concurrent smoking. Further defining the mechanism of injury may provide insight into methods to optimize outcomes in anemia management.

Figure 1

Consort Diagram Flow of Participants from CHOIR included in the Progression of Kidney Disease Analysis

Figure 2

Kaplan-Meier Plot of the Time to the First Progression of Kidney Disease Outcome (Doubling of Creatinine, RRT or Death) by Treatment Group and Smoking Status

Figure 3

Cumulative Incidence Plot of the Time to Doubling of Creatinine or RRT by Treatment Group and Smoking Status

Figure 4

Cumulative Incidence Plot of the Time to Death by Treatment Group and Smoking Status