A Japanese study just recently published in AJKD looked at dose responsiveness to ESA and effect on mortality. They defined 6 categories of ESA responsiveness based on a combination of ESA dosage. They studied the relationship between hemoglobin level, ESA responsiveness and outcomes among hemodialysis patients. The authors found that mortality in patients on hemodialysis may be affected by ESA responsiveness and by the interaction of hemoglobin and ESA dose. Low hemoglobin level and high ESA dose were strongly associated with an increased risk of mortality.
Dr Steven Fishbane and Azzour Hazzan wrote an editorial to the article in nature nephrology.
Dr Hazzan puts his thoughts as a post here as well:
Recently there have an intense interest in anemia in patients with CKD and how best to manage it. In the early years of dialysis, anemia was found to be more common in patients with CKD and associated with higher mortality. This has been proven through many studies albeit not of a good quality-RCTs. However; recently we have found that our approach to normalize the hemoglobin level may have been counterproductive. The reason being; increase stroke risks and probably higher cardiovascular mortality as well. Of the more definitive studies- the TREAT- looked at about 4000 patients with diabetic CKD-Non dialysis. The treatment arm was darbepoetin to achieve levels of 13 versus using darbepoetin to keep HGb from falling under 9. The investigators found that patients with hemoglobin artificially driven towards normal, had double fatal and non-fatal strokes risks. The question is why?
There are many stipulations. One possibility is the ESA dose effect? and patient's response to ESA.
The above mentioned study by Fukuma et al. has investigated the relationship between hemoglobin level, erythropoietin responsiveness and outcomes among Japanese hemodialysis patients. The authors found that mortality in patients on hemodialysis may be affected by ESA responsiveness and by the interaction of hemoglobin and ESA dose. Our editorial piece looks into that and other studies. Basically it would be hard with this kind of studies to make any definitive conclusions to answer this question. Is it the EAS dose or is it the fact that more severe anemia signify sicker patients and therefore higher mortality? In other words; acute and chronic illness, severity of illness, inflammation and co-morbidity are all highly intertwined with hemoglobin level and ESA dose, making analysis vulnerable to severe confounding variables.
In summary, we should exercise caution in treating anemia and use the lowest dose possible.
Post by Dr. Azzour Hazzan