What is Anemia of Chronic Renal Disease?
Anemia is typically identified when men have less than 13.0 g/dL in hemoglobin and premenopausal women have less than 12.0 g/dL. A particular type of anemia, linked with long-term kidney issues (Chronic Kidney Disease or CKD) is often linked to poor outcomes and an increased risk of death.
It begins to develop when the kidney’s filtration rate drops under 60 mg/ml. The anemia is unusual if the filtration rate, known as GFR, is above 80 mL/min/1.73 m2. As the GFR rate deteriorates, the anemia tends to worsen.
Anemia is frequently linked to poor outcomes in CKD patients. The current treatments for CKD-related anemia are still debated as some studies suggest that using drugs to stimulate red blood cell production can lead to health complications and death. The link between anemia and CKD was first noted 170 years ago by Richard Bright. As kidney disease progresses, anemia becomes more common, affecting nearly all patients in the advanced (stage 5) stage of CKD. This form of anemia often leads to a reduced quality of life and an increased risk of cardiovascular disease, cognitive impairments, hospital stays, and death.
What Causes Anemia of Chronic Renal Disease?
Anemia in patients with chronic kidney disease has multiple causes. The most commonly accepted one is reduced production of a hormone called erythropoietin, or EPO, by the kidneys. EPO is critical for the creation of red blood cells. Recently, scientists have discovered a link between the decreased amount of EPO and the reduction of a particular compound called hypoxia-inducible factor (HIF). HIF plays a vital part in activating the genes responsible for producing EPO.
There are also other factors that contribute to this type of anemia. These include a condition called uremia, which can deform red blood cells and cause them to break apart; deficiencies in folate and vitamin B12; a shortage of iron; abnormal platelet function leading to excessive bleeding; and occasionally, blood loss during kidney dialysis.
Additionally, the anemia can be worsened when red blood cells get damaged as they travel through the renal vasculature, or the network of blood vessels in the kidneys. This is especially noticeable in certain conditions like glomerulopathy (a type of kidney disease) and very high blood pressure. For this reason, anemia can be particularly severe in kidney diseases such as glomerulonephritis, diabetic kidney disease, relative to the level of kidney failure.
Risk Factors and Frequency for Anemia of Chronic Renal Disease
Anemia often develops when the kidneys lose more than 50% of their function. This tends to occur when a person’s glomerular filtration rate (or GFR, which is a measure of how quickly kidneys can filter blood) decreases to less than 60 mL/min/1.73 m2. As chronic kidney disease (CKD) worsens, anemia usually becomes more severe too. Despite this, the level of kidney function and anemia severity don’t always match up. In fact, nearly all patients who end up needing dialysis will eventually also develop anemia.
Anemia related to chronic kidney disease can result in a lower quality of life, greater risk of other health issues, increased death rates, and higher healthcare costs. Several studies have found that up to 60% of CKD patients who aren’t currently on dialysis also have anemia.
The incidence and severity of anemia in CKD patients tend to increase as the estimated glomerular filtration rate (eGFR, another measure of kidney health) decreases. Surveys have found that anemia is twice as common in CKD patients as in the general population.
Signs and Symptoms of Anemia of Chronic Renal Disease
Anemia related to chronic kidney disease shows the same symptoms as anemia from other sources. These symptoms include:
- Shortness of breath
- Tiredness
- General weakness
- Headaches
- Difficulty with concentration
- Dizziness
- Decreased ability to exercise
There are also some visible signs that might be noticed:
- Pale skin and eyes
- Breathing problems
- Rapid heart rate
- Chest pain (usually with very low red blood cell count)
- Heart failure (typically with long-term, severe low red blood cell count)
Testing for Anemia of Chronic Renal Disease
If your doctor suspects you’ve got a medical condition that’s causing changes in your blood, they might ask for several tests. These could include a complete blood count (CBC) and checking for different types of cells in your blood (differential). They’ll also want to check your levels of iron, B vitamins, and folate. Sometimes checking how your thyroid is working can be important, too, especially when it’s about particular types of anemia.
One particular blood disorder, called normocytic normochromic anemia, along with a lower than normal count of young red blood cells (reticulocytopenia), can be found with these tests.
Unfortunately, patients undergoing dialysis for chronic kidney disease (CKD) may not have accurate results when their iron levels are assessed with the standard tests. That’s because an ongoing inflammation might spike the levels of a protein called ferritin, which can store iron. A study called the Dialysis Patients’ Response to IV Iron With Elevated Ferritin, however, concluded that giving these patients iron through an IV can still be beneficial if their transferrin (a protein that binds with iron) saturation is less than 30%, even if they have really high levels of ferritin – up to 1200 ng/mL.
Furthermore, doctors generally don’t recommend measuring the levels of erythropoietin, a hormone that stimulates red blood cell production, in CKD patients. The reason is that unlike in healthy individuals, in kidney disease patients, the levels of erythropoietin don’t increase appropriately in response to severe anemia. That’s why it’s often referred to as a ‘relative erythropoietin deficiency’.
When doctors look at the bone marrow, they’ll typically see a reduced production of red blood cells, tying up with the observations of bone marrow’s resistance to erythropoietin in these patients.
Treatment Options for Anemia of Chronic Renal Disease
The usual treatment for anemia due to chronic kidney disease involves improving kidney function, when possible, and stimulating the production of red blood cells. This is usually achieved with the use of medications called erythropoiesis-stimulating agents (ESAs), along with iron supplementation.
Before the development of modern treatments, the main option was blood transfusions, which could lead to many complications such as infection, excess iron in the body, fluid overload, and reactions to the transfusion itself. In the 1970s, the use of male hormones (androgens) was introduced to avoid transfusions. This was further improved in the 1980s with the development of a medication based on a natural hormone produced by the body (recombinant erythropoietin or EPO) and other ESAs. These medications have not only helped avoid transfusions, but they’ve also increased survival rates, improved quality of life, enhanced heart function, decreased hospital stays and lowered costs.
The two main types of ESAs used today are recombinant human erythropoietin and darbepoetin alfa. They are quite similar, yet the latter has a longer half-life, meaning it can be administered less frequently.
The guidelines for using these medications depend on whether the patient is on dialysis or not. If they’re not on dialysis, ESAs are generally considered when their hemoglobin level drops below 10 g/dL. In dialysis patients, ESAs are usually avoided unless the hemoglobin level is between 9 and 10 g/dL. It’s important to note that the response to ESAs doesn’t happen instantly – it takes about 8 to 12 weeks for the red blood cell count to rise. In about 10 to 20% of cases, the anemia doesn’t respond well to the ESAs. Side effects can include seizures, high blood pressure, clotting at the site of dialysis access, faster growth of cancer cells, and higher mortality in cancer patients.
Regardless of whether the patient is on dialysis or not, the goal is to use ESAs to keep hemoglobin levels below 11.5 g/dL. Past trials have shown that higher levels of ESAs used to maintain hemoglobin levels above 11 g/dL can lead to greater risks including higher mortality, blood clots, and negative effects on the brain and heart.
Patients with chronic kidney disease often experience iron deficiency due to impaired absorption of dietary iron, bleeding, frequent blood tests, and blood loss during dialysis. Hence, iron supplementation forms a key part of treating anemia in these patients. Intravenous iron is usually preferred for patients on hemodialysis since they often have trouble absorbing oral iron. The acceptable levels for measures of iron in the body depend on whether the patient is on dialysis or not, and have to be balanced against the risk of toxicity and infections.
Unlike the general population, high levels of a substance in the blood (serum ferritin) do not predict the response to treatment in kidney failure patients. Also, there is no ideal level of erythropoietin (the hormone that stimulates red blood cell production) for defining anemia in patients with kidney failure. So, routine checks of erythropoietin levels are not suggested for these patients.
What else can Anemia of Chronic Renal Disease be?
When a doctor tries to figure out the cause of anemia related to chronic kidney disease, they will consider the following health conditions:
- Alcohol abuse
- Aplastic anemia (a condition where the body stops producing enough new blood cells)
- Complications from dialysis (a treatment for severe kidney disease)
- Underactive thyroid (hypothyroidism)
- Overactive thyroid (hyperthyroidism)
- Methemoglobinemia (a blood disorder)
- Sickle cell anemia
- Systemic lupus erythematosus (an autoimmune disease)
- Underactive adrenal glands (hypoadrenalism)
- Panhypopituitarism (a condition in which the pituitary gland does not produce normal amounts of some or all of its hormones)
- Overactive parathyroid glands (hyperparathyroidism), both primary and secondary
- Myelophthisic anemia (a reduction in red blood cells due to the replacement of bone marrow by other substances).
The doctor needs to carefully consider these conditions and perform appropriate tests to make the correct diagnosis.
What to expect with Anemia of Chronic Renal Disease
Many people suffering from kidney failure do not respond to treatment with a hormone called erythropoietin, which is key because it can predict future heart-related complications. The two primary causes of non-responsiveness are lack of iron and inflammation. High amounts of a protein called CRP can indicate a patient’s resistance to erythropoietin in those on dialysis. Therefore, iron supplements are often recommended to increase the treatment’s effectiveness.
Anemia related to chronic kidney disease is often associated with a condition known as cardiorenal anemia syndrome. Researchers have found that a decrease of 1 gram in the concentration of hemoglobin, a protein that carries oxygen in the blood, leads to a 42% increase in the enlargement of the left chamber of the heart in those with stage 5 chronic kidney disease (CKD). Cardiovascular disease is particularly common amongst these patients and even more deadly than for the general population.
A global study called the Dialysis Outcomes Practice Pattern Study (DOPPS) showed that when hemoglobin levels fall below 11 grams per deciliter, there is an increase in hospitalization and death rates in patients with CKD.
Possible Complications When Diagnosed with Anemia of Chronic Renal Disease
Anemia related to kidney disease is a separate risk factor that can lead to death. It’s been found to accelerate the enlargement of the left portion of the heart, the rate at which oxygen is used up in the body, and the chances of poor heart health outcomes. Moreover, this type of anemia can cause depression, tiredness, strokes, a decrease in the ability to exercise, and an increase in the rate of being admitted to the hospital
Long-term treatment of this anemia with a medicine called erythropoietin can cause high blood pressure, constriction of blood vessels, and seizures.
Preventing Anemia of Chronic Renal Disease
Patients with chronic kidney disease should understand that their condition might prevent their kidneys from producing enough erythropoietin, a hormone that regulates the production of red blood cells. As a result, they might experience a decrease in red blood cells, leading to a condition known as anemia. Many people with kidney disease develop anemia, which can actually start showing up early and progressively worsen as the disease advances.
Adjusting one’s diet can be a beneficial strategy in preventing or managing anemia that results from kidney disease. Consulting a dietitian for guidance on what to eat can significantly aid in this process.
Patients who are prescribed ESA or iron should follow the storage instructions provided by the manufacturer. For some products, refrigeration might be necessary. It’s also very important that patients with chronic kidney disease promptly report to their healthcare providers if they notice any signs of bleeding or if they exhibit symptoms suggestive of anemia.