Managing Anemia in Chronic Kidney Disease: Beyond Iron and ESAs

Anemia is a common issue in patients with chronic kidney disease (CKD), with up to 60% of those not on dialysis reported to have anemia.¹ The usual approach to managing anemia in CKD is with oral or IV iron supplements and erythropoiesis-stimulating agents (ESAs). These treatments, however, are not always effective or may not be deemed appropriate for those with a hemoglobin level above 10 g/dL. Additionally, despite high rates of anemia, it has been reported that only 45% of patients with anemia are tested for iron deficiency, and 86% of patients with confirmed iron deficiency are not treated.¹ While these statistics are appalling, it is fair to say that many providers may feel that they have nothing else to offer their patients. But this is not the case.

Put a Face On It

One of the first steps to better treatment is to realize the impact of the quality of life on someone with anemia. Common symptoms (depending on severity) include fatigue, cold intolerance, difficulty breathing, difficulty concentrating and sleeping, body aches, chest pain, dizziness, fainting, and irregular heartbeat. Consider the impact on adherence to medication regimens and diet and other lifestyle components among individuals who cannot concentrate or sleep well or are tired all the time. Also think about how many of these symptoms could be mistaken for other root issues (such as irregular heartbeat, chest pain, and difficulty breathing) and anemia could be completely overlooked or considered as part of the normal progression of CKD. Patients are unlikely to be motivated to make changes when beleaguered by such symptoms. A hemoglobin level of 10 g/dL is normally a cause for concern in any other disease state. Put an actual face on anemia and see the patient’s symptoms, motivations, and choices in a clearer context in which better manage anemia in CKD.

Investigate for Anemia in Chronic Kidney Disease

Anemia can be easy for a clinician to miss if they are not looking for it or it is not a priority. The 2012 KDIGO guidelines for managing anemia in CKD patients can help.

For CKD patients without anemia measure hemoglobin concentration when clinically indicated and then:³

• at least annually in patients with CKD stage 3
• at least twice per year in patients with CKD stage 4–5 not on dialysis
• at least every 3 months in patients with CKD stage 5 on hemodialysis and peritoneal dialysis

For CKD patients with anemia not being treated with an ESA, measure hemoglobin concentration when clinically indicated and then:³

• at least every 3 months in patients with CKD stage 3–5 (not on dialysis) and CKD stage 5 on peritoneal dialysis
• at least monthly in patients with CKD stage 5 on hemodialysis

Since the guidelines also recommend “when clinically indicated,” intake paperwork and routine visit questions should screen for initiation or worsening of anemia symptoms.

If anemia is discovered, the KDIGO guidelines recommend further investigation by ordering additional tests (regardless of CKD stage):³

• Complete blood count (CBC), which should include hemoglobin concentration, red cell indices, white blood cell count and differential, and platelet count
• Absolute reticulocyte count
• Serum ferritin level
• Serum transferrin saturation (TSAT)
• Serum vitamin B12 and folate levels

Ask Why

Once anemia is discovered, it is important to consider the root cause. Especially for CKD patients with a higher glomerular filtration rate, a lack of erythropoietin seems unlikely to be the primary culprit. Additional testing can help further pinpoint the issue, such as iron deficiency or folate or vitamin B12 deficiency. But it is important to go a step further and ask why. For example, placing patients on an oral vitamin B12 supplement to address a vitamin B12 deficiency is unlikely to be effective if they have been on a proton pump inhibitor for the past 5 years, something the treating clinician might have failed to consider. Deeper inquiries could have led to a different and effective treatment.

Anemia in Chronic Kidney Disease Is Multifactorial

Even when ordering additional testing and obtaining a detailed medical history, treatments can still fall short because anemia in chronic illness is complex and multifactorial. Systemic inflammation, reduced bone marrow response to erythropoietin due to uremic toxins, vitamin and mineral deficiencies, impaired nutrient absorption, and disordered iron homeostasis are some of the currently known contributors to anemia that are not typically addressed.¹ As an example, vitamin D is often low in those with CKD but plays an important role in promoting erythropoiesis, moving iron out of storage, and improving anemia related to inflammation.⁴ Vitamin D, however, traditionally has not been a typical consideration in anemia, but research has shown it to be an important factor.

There are no specific guidelines for treating anemia from a multifactorial perspective, and likely there will not be until providers can share their own clinical experience of approaches that do or do not help their patients. Nephology providers do not have to be alone in this multifactorial approach. Referring patients to a dietitian to help correct nutrient deficiencies and support gut health, coordinating additional testing, adjusting medications contributing to anemia, and being open to learning more about useful supplements can ensure that patients are receiving well-rounded care.

In the absence of clear guidelines, it can feel uncomfortable to consider treatments that may seem to have less gold-standard research backing them up. Still, it is well within the realm of evidence-based practice to use clinical judgment to consider interventions that can benefit CKD patients with anemia.  Approaching anemia with these fresh perspectives in mind, nephrology providers can help improve the quality of life of their patients, reduce costs, and improve renal survival.

Lindsey Zirker MS, RD, CSR is a renal dietitian and Director of Clinical Services for the Kidney Nutrition Institute in Titusville, Florida. She specializes in autoimmune kidney disease and advanced practice medical nutrition therapy for people with kidney disease. 

References

1. Portolés J, Martín L, Broseta JJ, Cases A. Anemia in chronic kidney disease: From pathophysiology and current treatments, to future agents. Front Med (Lausanne). 2021;8:642296. doi:10.3389/fmed.2021.642296.
2. National Institute of Diabetes and Digestive and Kidney Diseases. Anemia in chronic kidney disease.
3. KDIGO. KDIGO Clinical practice guideline for anemia in chronic kidney disease. Kidney Int Suppl. 2012;2(4):279-335.
4. Yee-Moon Wang A. Nutrition and anemia in chronic kidney disease. In: Kopple JD, Massry SG, Kalantar-Zadeh K, Fouque D, eds. Nutritional Management of Renal Disease. 4^th edition. Cambridge, Massachusetts: Academic Press. 2022:741-760. 

This article originally appeared on Renal and Urology News