Anemia Due to Chronic Kidney Disease

Why kidney disease causes anemia

Healthy kidneys sense how much oxygen the blood carries. When oxygen is low, they release erythropoietin (EPO), which travels to the bone marrow and drives red blood cell production. As kidney tissue is lost, EPO production falls and the marrow makes fewer red cells.

Other factors make it worse:

• Iron deficiency: reduced absorption from the gut, blood loss during dialysis and frequent blood tests.
• Functional iron deficiency: inflammation raises the hormone hepcidin, which locks iron away in storage so the marrow cannot use it, even when stores look adequate. This overlaps with anemia of chronic disease.
• Shorter red cell survival from uremic toxins.
• Vitamin B12 or folate deficiency.
• Bleeding from the gut, which is more common in kidney failure.
• Severe secondary hyperparathyroidism, which can scar the bone marrow.

Who gets it

Anemia becomes more likely as estimated GFR (kidney filtration rate) falls below about 60 ml/min, which is CKD stage 3. It is present in a large majority of people with stage 5 or on dialysis. People with diabetes tend to develop it earlier.

Symptoms

Anemia develops slowly, so people often adapt and blame symptoms on kidney disease or age.

• tiredness and low energy
• breathlessness on stairs or walking
• feeling cold
• pale skin and inner eyelids
• headaches and dizziness
• poor concentration and memory
• reduced exercise capacity
• restless legs, often with iron deficiency

Long-standing anemia makes the heart work harder and contributes to left ventricular thickening and heart failure, which are already common in CKD.

Diagnosis

Guidelines advise checking hemoglobin at least once a year in CKD stage 3, more often in stages 4 and 5 and on dialysis.

CKD anemia is a diagnosis made after other causes are excluded. Doctors also look for bleeding, especially from the bowel, when iron deficiency is present.

Treatment

Iron

Iron is usually the first step, because ESAs work poorly when iron is low.

• Oral iron is often tried first in people not on dialysis. Side effects include constipation and stomach upset.
• Intravenous iron is preferred on hemodialysis and when tablets fail or are not tolerated. It raises stores quickly.

Doctors monitor ferritin and TSAT to avoid iron overload.

Erythropoiesis-stimulating agents (ESAs)

ESAs such as epoetin alfa and darbepoetin are synthetic versions of erythropoietin, given by injection under the skin or into the dialysis line. Under KDIGO guidance they are usually considered when hemoglobin is below about 10 g/dL despite adequate iron. The target is to relieve symptoms and reduce transfusions, not to normalize hemoglobin. Aiming for high levels, above about 11.5 to 13 g/dL, raised the risk of stroke, blood clots and heart events in major trials.

ESAs can raise blood pressure, and are used with caution in people with active cancer or a past stroke.

HIF-PH inhibitors

Newer oral medicines such as daprodustat stimulate the body's own EPO production. In the US, daprodustat is approved for adults on dialysis. Availability and approved uses differ between countries.

Blood transfusion

Transfusions are reserved for severe or symptomatic anemia, rapid blood loss, or when ESAs do not work. Doctors try to limit them in people who may receive a kidney transplant, because transfusions can create antibodies that make finding a matching kidney harder.

Outlook

Treating anemia improves energy, exercise tolerance and quality of life, and reduces the need for transfusions. A successful kidney transplant usually restores EPO production and corrects the anemia within a few months.

Living with CKD anemia

• Keep up with blood tests, and report rising tiredness or breathlessness.
• Take iron tablets on an empty stomach if tolerated, separated from phosphate binders and calcium, which block absorption. Ask your team about timing.
• Do not take iron supplements without advice if you receive IV iron.
• Manage blood pressure, which ESAs can raise.
• Follow your kidney dietitian's guidance, as some iron-rich foods are also high in potassium or phosphorus.

Frequently asked questions

Why does chronic kidney disease cause anemia?

Damaged kidneys make less erythropoietin, the hormone that signals the bone marrow to produce red blood cells. Iron deficiency, inflammation that blocks iron use, blood loss during dialysis and shorter red cell lifespan add to the problem.

At what stage of kidney disease does anemia start?

It can begin at any stage but becomes more common from stage 3, when kidney function falls below about 60 percent of normal. Most people with stage 5 kidney disease or on dialysis have anemia, which is why hemoglobin is checked regularly.

What hemoglobin level is the target in CKD?

Guidelines generally avoid targeting normal levels. ESAs are usually started when hemoglobin is below about 10 g/dL, and doses are adjusted to avoid levels above about 11.5 g/dL. Higher targets increased stroke and heart risks in studies. Your kidney team sets your individual target.

Can anemia from kidney disease be cured?

It can be well controlled with iron and ESAs, but it usually persists while kidney function remains low. A successful kidney transplant typically restores erythropoietin production and corrects the anemia.