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A recent study provided new insights into the relationship between iron deficiency and cardiovascular events in patients with chronic kidney disease (CKD) who were receiving long-acting erythropoiesis-stimulating agents (ESAs). The findings published in the Journal of Nephrology suggest that maintaining higher levels of transferrin saturation (TSAT) may improve the cardiovascular outcomes for these population.
Long-acting ESAs like darbepoetin alfa have become common treatment for anemia in CKD patients. Despite the improvements in anemia management, the overall prognosis for these patients has not significantly improved. Iron deficiency is linked to the development of cardiovascular diseases (CVDs) and may be a contributing factor. ESAs can induce a state of relative iron deficiency which is potentially limiting the expected improvements on the patient prognosis. This study analyzed the association between iron deficiency and cardiovascular events in CKD patients who were treated with darbepoetin alfa with TSAT as a marker. TSAT is considered less susceptible to inflammation than ferritin which makes it a more reliable indicator of iron status.
The study included a total of 1,040 non-dialysis-dependent CKD patients who were at least 20 years old with a glomerular filtration rate of less than 60 mL/min/1.73 m² and hemoglobin levels below 11 g/dL. These patients were part of the BRIGHTEN Trial which evaluated ESA resistance in treating anemia in non-dialysis-dependent CKD. The analysis revealed that patients with TSAT levels of 30% or higher had a significantly better prognosis for cardiovascular events. Also, the adjusted hazard ratio for these patients was 0.34 (95% CI: 0.22–0.52) which suggests that higher TSAT levels were associated with a substantially lower risk of cardiovascular events.
Further stratified analysis showed that patients with TSAT levels between 30% and 40% had a significantly lower risk of cardiovascular events when compared to the patients with TSAT levels between 20% and 30%. The multivariate-adjusted hazard ratio for this group was 0.33 (95% CI: 0.21–0.54). These findings suggest that maintaining TSAT levels between 30% and 40% could lead to significantly fewer cardiovascular events in CKD patients treated with long-acting ESAs. This brings out the potential importance of closely monitoring and managing iron levels to improve cardiovascular outcomes in this patient population.
This study prompts to consider strategies to maintain higher TSAT levels in CKD patients who were undergoing ESA therapy. This could improve the responsiveness to treatment and reduce the risk of cardiovascular events by improving patient prognosis. Further research is needed to develop more targeted interventions to optimize iron levels and improve clinical outcomes for these patients.
Reference:
Nakai, K., Nishino, T., Kagimura, T., & Narita, I. (2024). Impact of transferrin saturation on cardiovascular events in non-dialysis-dependent chronic kidney disease patients treated with darbepoetin alfa. In Journal of Nephrology. Springer Science and Business Media LLC. https://doi.org/10.1007/s40620-024-02000-y