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Outcomes of Early Versus Delayed Anemia Treatment in Nondialysis-Dependent CKD
Kouji Kawai1, Manabu Ishii1, Yoshimasa Kokado1
1Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan.
Insights
Starting anemia treatment before hemoglobin drops below 9.0 g/dl in nondialysis-dependent chronic kidney disease (NDD-CKD) patients is crucial. Delayed treatment increases risks for cardiovascular events and mortality, though not renal outcomes.
Area of Science:
- Nephrology
- Cardiology
- Hematology
Background:
- Anemia is common in nondialysis-dependent chronic kidney disease (NDD-CKD) patients.
- The optimal timing for initiating erythropoiesis-stimulating agent (ESA) treatment based on hemoglobin levels remains unclear.
- Understanding the impact of delayed treatment on renal and cardiovascular outcomes is critical for patient management.
Purpose of the Study:
- To investigate the association between hemoglobin level at treatment initiation and renal and cardiovascular outcomes in NDD-CKD patients.
- To compare outcomes between patients receiving early (hemoglobin ≥9.0 g/dl) versus delayed (hemoglobin <9.0 g/dl) ESA treatment.
Main Methods:
- Retrospective cohort study using two Japanese real-world databases (MDV and RWD).
- Patients initiating long-acting ESA treatment were categorized into early or delayed treatment groups based on pre-treatment hemoglobin levels.
- Propensity score matching was employed to balance baseline characteristics; primary and secondary composite outcomes, including renal events, cardiovascular events, and all-cause mortality, were analyzed.
Main Results:
- Delayed ESA treatment was not significantly associated with an increased risk of the composite renal outcome in either database.
- However, delayed treatment was linked to significantly higher risks of the composite cardiovascular outcome, heart failure, and all-cause mortality in both MDV and RWD cohorts.
- Hazard ratios for cardiovascular composite outcomes ranged from 1.34 to 1.47, and for all-cause mortality from 1.64 to 1.83, indicating increased risks with delayed intervention.
Conclusions:
- Delaying anemia treatment in NDD-CKD patients until hemoglobin levels fall below 9.0 g/dl does not increase renal event risk but significantly elevates risks for cardiovascular events and all-cause mortality.
- These findings underscore the importance of early anemia management in NDD-CKD to mitigate serious cardiovascular complications and improve survival.
- Early intervention with ESAs before hemoglobin drops below 9.0 g/dl is recommended for NDD-CKD patients.
Introduction:
The association of hemoglobin level at treatment initiation with renal and cardiovascular outcomes in patients with anemia in nondialysis-dependent (NDD) chronic kidney disease (CKD) is unclear.
Methods:
This retrospective cohort study utilized 2 Japanese databases (Medical Data Vision Co. Ltd., Tokyo, Japan [MDV]; and Real World Data Co. Ltd, Kyoto, Japan [RWD]). Patients initiated on long-acting erythropoiesis-stimulating agent (ESA) treatment were divided into early (hemoglobin levels ≥9.0 g/dl) and delayed (<9.0 g/dl) treatment groups. The primary outcome was a renal composite (renal replacement therapy, ≥50% estimated glomerular filtration rate [eGFR] reduction, eGFR <6.0 ml/min per 1.73 m2, and all-cause mortality), and secondary outcomes were a cardiovascular composite (hospitalization by ischemic heart disease, including myocardial infarction, hospitalization by stroke and heart failure, and cardiovascular death) and components of the composite outcomes.
Results:
After propensity score matching, 1472 (MDV) and 1264 (RWD) patients were evaluated. Delayed treatment was not associated with a risk of the renal composite outcome (MDV: hazard ratio [HR]: 1.15, 95% confidence interval [CI]: 0.99-1.33; RWD: HR: 1.08, 95% CI: 0.92-1.28). However, delayed treatment was associated with higher risks of the cardiovascular composite outcome (MDV: HR: 1.47, 95% CI: 1.16-1.84; RWD: HR: 1.34, 95% CI: 1.09-1.64), heart failure (MDV: HR: 1.50, 95% CI: 1.13-2.00; RWD: HR: 1.53, 95% CI: 1.20-1.96) and all-cause mortality (MDV: HR: 1.83, 95% CI: 1.32-2.54; RWD: HR: 1.64, 95% CI: 1.21-2.22).
Conclusion:
Although the risk of renal events was not increased following delayed treatment of anemia in patients with NDD-CKD, the risks of cardiovascular events and all-cause mortality were increased, suggesting the importance of early intervention before hemoglobin falls below 9.0 g/dl.
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