Nephrogenic anaemia is a condition in which your blood lacks enough healthy red blood cells or haemoglobin, directly linked to damaged kidneys that cannot function properly. When kidneys lose their ability to work as they should, they often fail to produce a vital hormone needed for red blood cell creation, leaving the body struggling to deliver oxygen to tissues and organs where it is needed most.

Understanding Nephrogenic Anaemia

Nephrogenic anaemia, also known as anaemia of chronic kidney disease, occurs when the kidneys can no longer perform one of their hidden but crucial tasks. While most people know that kidneys filter waste from the blood, fewer realise that healthy kidneys also produce a hormone called erythropoietin, often shortened to EPO. This hormone acts as a signal to the bone marrow, telling it to make red blood cells. When kidneys become damaged, they produce less erythropoietin, which means the bone marrow receives weaker signals and creates fewer red blood cells than the body needs.^[1]

Red blood cells contain a protein called haemoglobin, which is rich in iron and carries oxygen from the lungs to every part of the body, including the heart, brain, muscles, and other organs. When there are not enough red blood cells or when haemoglobin levels drop too low, tissues and organs may not receive the oxygen they need to work properly. This oxygen shortage can make daily tasks feel exhausting and affect how well the body functions overall.^[1]

How Common Is This Condition

Nephrogenic anaemia is a widespread complication among people living with chronic kidney disease. The condition is less common in the early stages of kidney disease, but as kidney function declines and the disease progresses, anaemia becomes increasingly likely and often more severe. Almost all patients who reach stage 5 chronic kidney disease, the most advanced stage, experience some degree of anaemia.^[10]

The prevalence of anaemia rises in direct relation to the extent of kidney damage. When creatinine clearance, a measure of kidney function, falls below 45 millilitres per minute, anaemia typically begins to appear. The severity of anaemia does not always match the level of kidney dysfunction perfectly, as other factors also play a role. However, the general pattern is clear: the worse the kidney disease, the more likely and severe the anaemia becomes.^[5]

What Causes Nephrogenic Anaemia

The primary cause of nephrogenic anaemia is the kidney’s failure to produce enough erythropoietin. Healthy kidneys are responsible for about 90 percent of the body’s erythropoietin production. This hormone is made by specialised cells in the kidneys called interstitial fibroblasts, also known as type I interstitial cells. When kidney tissue becomes damaged by disease, these cells can no longer produce adequate amounts of the hormone, and the bone marrow does not receive the signal it needs to manufacture enough red blood cells.^[6]

However, the story does not end with reduced hormone production. In people with advanced chronic kidney disease, the causes of anaemia become more complex and intertwined. Blood loss is common due to multiple blood tests, problems with blood clotting caused by poorly functioning platelets, and complications related to dialysis treatment. Some patients also develop abnormal blood vessels called angiodysplasia, which can bleed.^[5]

Another contributing factor is that the bone marrow itself may become less responsive to whatever erythropoietin is present, a phenomenon called marrow resistance. This means that even if some hormone reaches the bone marrow, the cells do not respond as strongly as they should. Additionally, substances that build up in the blood when kidneys fail, collectively called uraemia, can shorten the lifespan of red blood cells. Normally, red blood cells live for about 120 days, but in kidney disease, this can drop to 70 to 80 days or even less.^[6]

Iron deficiency is another important piece of the puzzle. Even with adequate erythropoietin, the body cannot make red blood cells without sufficient iron. Damaged kidneys affect iron metabolism in several ways. They fail to produce a substance called erythroferrone, which normally suppresses a hormone called hepcidin. When hepcidin levels rise, iron becomes trapped inside cells and cannot be used for making red blood cells, creating what is called functional iron deficiency.^[5]

Who Is at Greater Risk

The risk of developing nephrogenic anaemia is directly tied to the severity of chronic kidney disease. Anyone with kidney damage that affects the organ’s ability to filter blood properly is at risk, but the likelihood increases significantly as kidney disease progresses through its stages. People who have reached more advanced stages of chronic kidney disease, particularly those approaching or at stage 5, face the highest risk.^[1]

Certain underlying conditions that cause kidney disease may place people at greater risk for developing more severe anaemia. Diabetes that has damaged the kidneys, a condition called diabetic nephropathy, is particularly associated with anaemia. Similarly, those with amyloidosis affecting the kidneys often experience more pronounced anaemia. The type of kidney damage matters because different diseases affect the kidney’s hormone-producing cells in different ways.^[5]

People receiving long-term dialysis treatment are especially vulnerable to anaemia. The dialysis process itself can contribute to blood loss, and these patients typically have very limited remaining kidney function. Their bodies have lost nearly all ability to produce erythropoietin naturally, making them dependent on medical interventions to maintain adequate red blood cell levels.^[5]

Recognising the Symptoms

The symptoms of nephrogenic anaemia often develop gradually, making them easy to miss or attribute to other causes. The most common complaint is profound tiredness or fatigue that does not improve with rest. This exhaustion can be so severe that even simple daily activities, like walking to another room or preparing a meal, become challenging and draining. Many people describe feeling as though they have no energy at all, making it difficult to maintain their usual routines or participate in activities they once enjoyed.^[4]

Breathing difficulties are another hallmark symptom. People with nephrogenic anaemia often feel short of breath after only minimal exertion, such as climbing a few stairs or carrying light objects. Some may feel breathless even while resting. This happens because the body’s tissues are not receiving enough oxygen, and the lungs try to compensate by working harder. The sensation can be frightening and may worsen as anaemia becomes more severe.^[1]

Physical weakness is common, with muscles feeling weaker than usual. Tasks that once seemed effortless may suddenly require significant effort. Some people notice that their muscles tire quickly during physical activity, or they may struggle with activities that require sustained strength. This muscle weakness stems from inadequate oxygen delivery to muscle tissue.^[4]

Many people with nephrogenic anaemia experience dizziness or light-headedness, sometimes feeling as though they might faint. These sensations often worsen when standing up quickly or after physical activity. The brain is highly sensitive to oxygen levels, and even small deficits can affect balance and alertness. Some individuals also report difficulty concentrating, confusion, or trouble thinking clearly, which can interfere with work, studies, or daily decision-making.^[14]

Changes in appearance can provide visible clues to anaemia. The skin may look unusually pale, lacking its normal healthy colour. This pallor can be particularly noticeable in the face, palms, or inner eyelids. In some cases, fingernails or lips may take on a bluish tint, indicating poor oxygen levels in the blood. Some people feel cold even when others around them are comfortable, as the body struggles to maintain warmth with reduced oxygen-carrying capacity.^[14]

Other symptoms include persistent headaches, an irregular or rapid heartbeat, and disturbed sleep patterns. The heart may beat faster than normal as it attempts to compensate for the reduced oxygen in the blood by pumping more frequently. Some people experience irritability or mood changes, becoming frustrated more easily than usual, particularly when they struggle to complete everyday tasks. In some cases, people may develop unusual cravings for non-food items such as ice, clay, starch, or dirt, a condition called pica.^[14]

Sexual function may also be affected, with some individuals experiencing problems with libido or, in men, difficulty maintaining erections. These symptoms can compound the emotional and psychological burden of living with chronic kidney disease and anaemia.^[14]

Potential Complications

Left untreated or poorly managed, nephrogenic anaemia can lead to serious complications that affect multiple body systems. The heart is particularly vulnerable. When tissues do not receive enough oxygen, the heart must work harder to pump blood throughout the body. Over time, this extra workload can strain the heart muscle and potentially lead to heart problems, including an increased risk of heart attack, heart failure, or dangerous irregular heartbeats called arrhythmias.^[1]

People with nephrogenic anaemia face a higher risk of developing cardiovascular disease, which includes conditions affecting the heart and blood vessels. This risk is particularly concerning because many of the underlying causes of kidney disease, such as high blood pressure and diabetes, also contribute to heart disease. The combination of kidney disease and anaemia creates a dangerous cycle that can accelerate damage to both organs.^[11]

The brain also suffers when oxygen delivery is compromised. Chronic oxygen deprivation can affect cognitive function, including memory, concentration, and the ability to process information. In severe cases, inadequate oxygen to the brain can contribute to confusion and impaired decision-making abilities. These cognitive effects can significantly impact a person’s independence and quality of life.^[1]

Overall mortality risk increases in people with chronic kidney disease who have anaemia. Studies have shown that anaemia is associated with poorer outcomes and higher death rates among those with kidney disease. This highlights the importance of recognising and treating anaemia as part of comprehensive kidney disease management.^[10]

Quality of life deteriorates markedly when anaemia goes untreated. The persistent fatigue, weakness, and breathlessness prevent people from engaging in normal activities, socialising, working, or enjoying hobbies. Many people find themselves withdrawing from social situations and becoming increasingly isolated, which can contribute to depression and anxiety. The physical limitations imposed by anaemia can make people feel dependent on others and rob them of their sense of autonomy.^[10]

How the Condition Affects Body Function

The chain of events in nephrogenic anaemia begins deep within the kidneys. Specialised cells that normally detect low oxygen levels and respond by producing erythropoietin become damaged or destroyed by kidney disease. This disrupts the body’s natural feedback system for maintaining adequate red blood cell numbers. In a healthy person, when oxygen levels drop, the kidneys sense this change and increase erythropoietin production, which stimulates the bone marrow to create more red blood cells. In kidney disease, this feedback loop breaks down.^[4]

Without sufficient erythropoietin signalling, the bone marrow reduces its production of red blood cells. This leads to a condition called hypoproliferative anaemia, meaning the bone marrow is not making enough new cells to replace those that naturally die off. The result is a gradual decline in the total number of red blood cells circulating in the bloodstream.^[5]

The anaemia in kidney disease is typically described as normocytic and normochromic, medical terms meaning that the red blood cells that are produced are normal in size and colour. The problem is not with the quality of individual cells but with the quantity. There simply are not enough of them to meet the body’s oxygen needs.^[10]

As kidney disease advances, other mechanisms compound the problem. The accumulation of waste products in the blood, known as uraemic toxins, creates a hostile environment for red blood cells. These toxins can damage the cell membranes of red blood cells, causing them to break down prematurely, a process called haemolysis. This may occur inside blood vessels or outside them as cells are destroyed by the spleen and other organs. The shortened lifespan of red blood cells means that even the reduced number being produced by the bone marrow do not last as long as they should.^[6]

Iron metabolism becomes severely disrupted in kidney disease. The lack of erythroferrone production leads to increased levels of hepcidin, a hormone produced by the liver. Elevated hepcidin prevents iron from being released from storage sites in the body, such as the liver and macrophages, special immune cells that normally recycle iron from old red blood cells. Iron also cannot be absorbed properly from food in the intestines. This creates a situation where the body may have iron stores, but that iron is locked away and unavailable for making new red blood cells, resulting in functional iron deficiency.^[5]

The bone marrow may also become less responsive to whatever erythropoietin is present, though the exact reasons for this resistance are not fully understood. Chronic inflammation, which often accompanies kidney disease, plays a role. Inflammatory substances called cytokines, including interleukins and tumour necrosis factor, can interfere with red blood cell production and reduce the number of erythropoietin receptors on bone marrow cells. This means that even if erythropoietin levels are artificially increased through medication, the bone marrow may not respond as vigorously as expected.^[6]

In people receiving dialysis, the physical process of filtering blood through the dialysis machine can cause additional blood loss. Small amounts of blood remain in the dialysis tubing and filters after each session, and some people experience bleeding due to the blood thinners used during dialysis to prevent clotting in the machine. Frequent blood tests required for monitoring kidney disease and other conditions also contribute to ongoing blood loss.^[6]

Some people with kidney disease develop secondary hyperparathyroidism, a condition where the parathyroid glands become overactive. This can affect bone marrow function and contribute to anaemia. The complex interactions between mineral metabolism, bone health, and blood cell production add another layer of complexity to understanding and managing anaemia in kidney disease.^[5]