Anemia of CKD: Challenges With Traditional Anemia Treatment

Key Takeaways

• For younger patients with anemia of chronic kidney disease, transfusions increase the possibility of becoming allosensitized, which may diminish their likelihood of being a viable transplant candidate in the future.
• Transfusing patients in their 60s who still may be candidates for a transplant also has associated risks, such as precipitating heart failure.
• Better therapy for anemia of chronic kidney disease is needed because we should not be transfusing patients, particularly older patients.

Two aspects of anemia treatment that I think healthcare professionals should be aware of were revealed in a study by St Peter and colleagues looking at datasets of patients with chronic kidney disease (CKD) with and without anemia who were stage III-V but not dialysis dependent. Two categories of patients were assessed: commercially insured patients aged 18-63 years (a younger population) and Medicare-covered patients aged 66-85 years (an older population). Of the commercially insured patients, 11% were being treated with an erythropoiesis-stimulating agent (ESA), and 12% were being treated with blood transfusions. Many younger patients were being treated with transfusions instead of conventional ESAs. This is important to note because many of these patients are potential transplant candidates. By receiving blood transfusions, the possibility of allosensitization increases, which diminishes the likelihood of their being a viable transplant candidate.

The second point was demonstrated by the group of patients covered by Medicare, who were older, retired patients. Only 13% were being treated with an ESA, and 22% were being treated with a blood transfusion. Some of these patients also will be transplant candidates, as we still transplant patients who are in their 60s. However, many of these patients develop other comorbidities, such as underlying heart failure and other forms of cardiovascular disease. Transfusing these patients has risks, such as precipitating heart failure due to possible volume overload. 

Therefore, for the 2 reasons above, I think the current treatment situation is really suboptimal. We do not want to be transfusing our patients. We want an effective treatment for anemia of CKD that can target both younger and older patients and ideally correct their anemia to the recommended target range. We want to avoid the idea that these patients must get transfused.

Challenges Associated With Traditional Management of Anemia of CKD
In the United States, there are 2 categories of patients with CKD: those who are not on dialysis and those who are. Among the patients who are not on dialysis, the challenge is that many must go to a clinic for therapy. Not everyone lives near a center where they can get the drug administered, and my own research and research from others have detected disparities. Black patients, older patients, and people from resource-limited settings may have difficulty with transportation and accessing care, so these patients tend to stay anemic due to not receiving appropriate treatment. Most patients who have anemia who are not on dialysis could get anemia treatment, but again, people from resource-limited settings are not receiving treatment, and that is a real problem. Thus, oral therapies might help solve that problem.

More than 500,000 patients in the United States on dialysis have end-stage kidney disease (ESKD). These patients have nonfunctioning kidneys, and almost all patients require treatment for anemia. Patients on hemodialysis can receive treatment for anemia during their hemodialysis session. However, approximately 13% of patients with ESKD are not on hemodialysis and instead are receiving home therapies. Most of these patients are on peritoneal dialysis and are injecting the drug subcutaneously. Again, to receive treatment for anemia, patients must go to a center, or they must inject it themselves—an option most patients do not like, as there are some adverse events. 

I think the current state of affairs is not optimal, and it would be great to have a form of therapy that would allow patients better access and provide more availability of treatment for their anemia than currently exists. I also think we all can agree that a better therapy is needed, because we should not be transfusing patients unless it is absolutely necessary. It is our responsibility, as healthcare professionals, to be aware of transfusion risks and know that we should be seeking better alternatives for treatment for our patients.

Because we have not had an update in the Kidney Disease: Improving Global Outcomes guidelines in more than 10 years, we are still basing our treatment paradigms on the interpretation of evidence generated more than a decade ago. However, there are emerging treatment options, including the hypoxia-inducible factor (HIF) prolyl hydroxylase (PH) enzyme inhibitors. HIF PH inhibitors function by stabilizing the HIF complex and can stimulate endogenous erythropoietin production in patients with ESKD. I am excited about these agents because I led the ASCEND clinical trial program, which evaluated the safety and efficacy of daprodustat, and I would love to have an alternative option available for patients. I hope we will have FDA approval early in 2023.

Your Thoughts?
In your practice, how do you manage treatment options for your patients with anemia of CKD? Please answer the polling question and join the conversation by posting a comment in the discussion section below.