When your kidneys sense that they’re not getting enough oxygen, they produce a hormone, called erythropoietin, which stimulates the production of red blood cells in your bone marrow. 

In the advanced stages of chronic kidney disease (CKD), your kidneys aren’t able to assess oxygen levels. As a result, your erythropoietin levels go down, which in turn lowers red blood cell production, causing anemia.*

A series of brief videos by Jay B. Wish, M.D., professor of clinical medicine at Indiana University School of Medicine and Chief Medical Officer (CMO) for dialysis at Indiana University Health (IUH) in Indianapolis, explores the:

• Challenges of managing CKD-related anemia
• Treatment approaches for anemia in high-risk patients
• Areas for improvement in anemia management
• Connection between anemia and quality of life for people with CKD

Challenges of anemia management in CKD

According to Dr. Wish, the challenges of managing anemia depend on whether or not the person is on dialysis. About 15% to 20% of dialysis patients don’t achieve target hemoglobin levels, despite increasing doses of erythropoietin-stimulating agents (ESAs) and intravenous iron. For these patients, the challenge is avoiding iron overload and oxidation.

Those not on dialysis face the issue of having to administer their ESAs and IV iron themselves or finding someone to do it for them. Their situation is further complicated by FDA restrictions, which state to not start administering ESAs until a patient’s hemoglobin drops below 10—but also cautions to start tapering off the ESAs once the hemoglobin goes above 10. 

Treatment for high-risk patients with anemia and CKD

Cardiovascular disease (CVD) is the biggest risk for people with stage 3 CKD or above. A person in stage 3 is 10 times more likely to die from CVD than they are to reach the need for dialysis from kidney failure. 

The majority of patients on dialysis usually die from cardiovascular events, such as:

• Myocardial infarction
• Heart failure
• Stroke

Studies have shown that increasing levels of hemoglobin doesn’t reduce that risk. For this reason, the most effective treatment for patients with CVD (and those at high risk of developing it) is to continue focusing on lowering the risk of cardiovascular events through the usual combination of diet, exercise, smoking cessation, and medication. 

New approvals and treatments for anemia management

One of the more promising new anemia treatments currently in development is HIF-PH inhibitors (HIF-PHI), also known as hypoxia-inducible factor stabilizers (HIF-stabilizers). This is a new class of drugs that carries potential benefits for non-dialysis-dependent CKD patients. 

Unlike ESAs, HIF-PHI drugs are made up of small molecules, enabling them to be taken orally as pills instead of requiring injection. 

The expectation and hope are that these drugs will:

• Improve iron absorption and metabolism
• Reduce the risk of cardiovascular events
• Increase patient compliance with treatments

Opportunities for improvement

It’s estimated that more than 2 million people living with non-dialysis-dependent CKD are also living with untreated, or inadequately treated, anemia. Reasons for this include the aforementioned inconvenience of patients having to self-inject ESAs and iron, finding someone willing to inject both for them, or traveling to a medical facility for the injections.

Another barrier to treatment is the “black box warning” on ESAs. A black box warning is the U.S. Food and Drug Administration’s (FDA) strongest warning for drugs and medical devices that can have serious side effects causing injury or death. The high toxicity of ESAs, coupled with the FDA’s stringent rules for the drugs’ administration, creates significant challenges to prescribing dosages that are both safe and effective—hence the excitement surrounding the new class of drugs for this patient demographic.

Relationship between anemia and quality of life

Studies using the Kidney Disease Quality of Life (KDQOL) survey tool show that physical components of the disease, including low hemoglobin levels that signal anemia, are primary factors in low quality of life scores. Therefore, it makes sense that treating anemia and alleviating its symptoms would improve patients’ quality of life.

Due to issues of potential bias and ethical questions concerning non-treatment of critically ill patients, clinical trials involving placebos weren’t conducted when ESAs were approved by the FDA 31 years ago. As a result, there’s no quantifiable evidence that those drugs accomplish the goal of improving the quality of life for CKD patients with anemia.

Fortunately, the new classes of drugs are being tested in double-blind, randomly-controlled clinical trials before being submitted for FDA approval. The new treatment options that appear to be heading to market tentatively signal good news for those living with CKD, whether on dialysis or not.

*Wish, J. B. (2020, Oct. 1). Anemia Management in CKD Video Perspectives. Healio. https://www.healio.com/news/nephrology/resources/anemia-management-in-ckd-video-perspectives/jay-b-wish-md