Uremia: Kidney Toxicity and Treatment

Uremia, sometimes referred to as uremic syndrome, is a dangerous condition in which your kidneys are unable to filter a waste product called urea from your blood.

Urea, a primary component of urine, is normally removed from the body when you pee (urinate). However, when the kidneys are no longer working—referred to as kidney failure—urea can accumulate to toxic levels.

Uremia is most often due to kidney failure from advanced chronic kidney disease (CKD). Common symptoms include nausea, vomiting, weight loss, lower-stomach pain, and fatigue. Without treatment in the form of dialysis or a kidney transplant, uremia can get progressively worse, leading to seizures, coma, and death.

This article describes the symptoms and causes of uremia, including how this potentially deadly complication of kidney disease is diagnosed and treated.

Emergency Uremia Symptoms to Diagnose

Uremia is a consequence of kidney failure, the end stage of CKD (also known as end-stage renal disease or ESRD). It can also occur with an acute kidney injury if the loss of kidney function is rapid and extreme.

The symptoms of uremia can be vague at first but become increasingly more pronounced as urea and other toxins accumulate in the bloodstream.

Common Symptoms

Prior to the onset of symptoms, increases in blood urea may be entirely asymptomatic (a state referred to as azotemia). With CKD, this can last for many years or decades, depending on how slowly or quickly kidney function is deteriorating. When symptoms of uremia do develop, they can often be nonspecific (very general) and easily attributed to other causes.

Common signs and symptoms of uremia include:

• Fatigue
• Weakness
• Sleepiness
• Nausea and vomiting
• Loss of appetite (anorexia)
• Headaches
• Muscle cramps
• Itching (pruritus)
• Difficulty concentrating
• Forgetfulness
• Difficulty sleeping (insomnia)
• Metallic taste in the mouth

There is no consistent point at which azotemia becomes symptomatic uremia. In most people, uremic symptoms develop when a urine test called a creatinine clearance (CrCl) falls below 10 milliliters per minute (mL/min). CrCl levels this low are clear indications of kidney failure.

Uremic symptoms can occur at higher CrCl levels. Even so, uremia related to CKD only occurs with kidney failure and, as such, is always treated as a medical emergency.

Advanced Symptoms

Despite how general early symptoms are, uremia can rapidly progress, depending on how quickly toxins accumulate. As kidney function continues to deteriorate, the severity of symptoms will increase and the prognosis (likely outcome) will worsen.

Signs and symptoms of untreated uremia include:

• A urine- or ammonia-like breath odor (uremic fetor)
• Yellowish crystals on your skin after sweat dries (uremic frost)
• Shortness of breath (dyspnea)
• Rapid, shallow breathing (tachypnea)
• Trouble breathing when lying down
• Heart palpitations
• Chest pain (angina)
• Swelling of the lower extremities (edema)
• A buildup of fluid in the abdomen (ascites)
• Muscle pain (myalgia)
• Bone pain (osteodynia)
• Loss of coordination
• Tremors and twitches
• Jerky eye movements (nystagmus)
• Uncontrollable leg movement (restless legs syndrome)
• Prickly or burning sensations of the hands or feet (peripheral neuropathy)
• Muscle wasting (cachexia)
• Seizures

Effect of Uremia on Organ Systems 

Urea itself is toxic to tissues, but that alone doesn’t account for uremia symptoms. Kidney failure also causes the accumulation of other waste products normally excreted from the body in urine when levels are extremely high, including:

• Creatinine (which can shorten the life span of red blood cells)
• Cyanate (which can cause drowsiness)
• Polyols (which can trigger peripheral neuropathy, damage to nerves outside the central nervous system, made up of the brain and spinal cord)

Together, these toxins can disrupt the delicate balance of fluids, electrolytes, hormones, and acids that your body needs to function normally. Different organ systems are affected in different ways.

Blood Complications

The kidneys are responsible for producing a hormone called erythropoietin (EPO) that stimulates the production of red blood cells. Damaged kidneys produced far less EPO, resulting in fewer red blood cells and a type of anemia called anemia of chronic disease.

Uremic toxins can also prevent platelets (the type of blood cell involved in clotting) from sticking together as they normally would. This can lead to coagulopathy in which impaired blood clotting causes easy bleeding, including gastrointestinal bleeding.

Bone Complications

Uremia is associated with decreases in calcium (hypocalcemia) and increases in phosphate (hyperphosphatemia). These important electrolytes help regulate the parathyroid gland, which maintains normal calcium levels in the body by releasing calcium from bones.

However, when calcium levels are very low and phosphate levels are very high, the parathyroid gland overproduces parathyroid hormone, causing too much calcium to be released. This can lead to osteodystrophy (kidney bone disease), a condition characterized by chronic bone pain and an increased risk of fractures.

Heart Complications

Uremia can cause uremic cardiomyopathy, a condition in which the left ventricle of the heart starts to thicken and become less flexible due to scarring. This reduces the heart’s ability to pump blood to the rest of the body, resulting in congestive heart failure.

Other complications of uremic cardiomyopathy include:

Brain Complications

Uremia can profoundly affect the central nervous system, causing uremic encephalopathy. This is a complication of kidney failure characterized by the following:

• Fatigue
• Weakness
• Headache
• Involuntary muscle movements
• Cramps
• Memory problems
• Seizures
• Coma

Uremic encephalopathy is not only caused by high urea levels but also by increases in parathyroid hormone, which directly contributes to “brain fog” and changes in mental status.

Also contributing is a condition called metabolic acidosis in which uremic toxins damage parts of the kidney that regulate the acid-base balance in the body. High blood acid can disrupt normal brain function and lead to shock, coma, and death when excessively high.

Other Complications

Hyperkalemia (high potassium levels) is a major concern with end-stage kidney disease. When potassium levels are excessively high, life-threatening arrhythmias, muscle weakness, or paralysis can occur.

Taking certain drugs can worsen the situation, including:

Other possible complications of uremia include:

• Impaired growth in children
• Absence of periods (amenorrhea)
• Loss of sex drive (low libido)
• Infertility
• An increased risk of infection
• Malnutrition due to anorexia and vomiting

Hospitalization and Treatment for Uremia

No matter if uremia is caused by chronic kidney disease or acute kidney injury, the aim of treatment is to replace the function of your kidneys.

This can be accomplished in one of the following three ways:

• Hemodialysis: This form of dialysis involves a machine that takes blood from a vein, filters out waste, and returns it to the body in a continuous, contained loop.
• Peritoneal dialysis: This form of dialysis uses the lining of your abdomen to filter blood using a special fluid that is washed in and out of your abdomen in regular cycles.
• Kidney transplantation: This is the replacement of a damaged kidney with a healthy kidney from a live or deceased donor.

People with symptomatic uremia should be treated with dialysis, without regard to the results of kidney function tests.

Those with acute kidney injury can often be treated with dialysis alone if the underlying cause is identified and properly treated. In such cases, normal kidney function may be restored.

The same is not true with uremia due to CKD. In such instances, damage to the kidneys is largely irreversible, and dialysis is often regarded as an interim measure until a donor kidney is available. For some, dialysis may be the only option if they are not candidates for a transplant.

Medications

No medications can directly treat uremia. With that said, certain medications may be prescribed to manage the symptoms or complications associated with uremia.

Examples include:

Uremia While on Dialysis

When uremia is due to end-stage kidney disease, dialysis can extend life and improve symptoms, but it may not erase all of the symptoms of uremia.

In 2020, researchers from Johns Hopkins University issued questionnaires to 1,954 adults on dialysis to evaluate the persistence of uremic symptoms while on life-extending treatment.

According to the findings published in the journal Kidney360, more than 80% of the respondents reported three or more symptoms after starting dialysis, while over 50% reported five or more symptoms.

Even after one year, respondents on dialysis still reported significant rates of uremic symptoms, including:

• Fatigue: 89%
• Sleepiness: 87%
• Pain: 85%
• Itchiness: 74%
• Difficulty concentrating: 60%
• Loss of appetite: 43%
• Nausea and vomiting: 40%

Comparatively, people on peritoneal dialysis were more likely to experience nausea and vomiting but less likely to have loss of appetite than those on hemodialysis. No significant differences were observed for the other symptoms.

This further highlights the need to adhere to lifestyle recommendations if diagnosed with kidney failure, including the appropriate diet and exercise. Keeping as healthy as possible is arguably the best way to cope with the rigors of dialysis.

Uremia and Kidney Transplant

When uremia is caused by end-stage kidney disease, the only “cure” is a kidney transplant. The main challenge of transplant surgery is that it can take months or years to get to the top of the waiting list. You will also need to take drugs known as immunosuppressants for the rest of your life to avoid organ rejection.

Even so, the benefits of a transplant can be enormous, normalizing kidney function and extending life for years and even decades.

Is Uremia Preventable?

If you have chronic kidney disease, the best way to prevent uremia is to avoid disease progression. This means identifying your risk factors for CKD progression—including modifiable risk factors you can adjust (like diet and smoking) and non-modifiable ones you can’t (like age and family history).

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) recommends the following lifestyle recommendations to avoid progression of CKD:

• Eat a healthy, balanced diet low in animal fat and high in fruits, vegetables, and whole grains.
• Restrict your salt intake to less than 2.3 grams per day (roughly 1 teaspoon).
• Limit your sugar intake to no more than 10% of your daily calories.
• Do at least 150 minutes of moderate-intensity exercise per week, exercising on most days.
• Lose weight if you are overweight or have obesity,
• Stop smoking, which increases blood pressure and places additional stress on the kidneys.
• Aim for seven to eight hours of sleep each night.

In addition, avoid nonsteroidal anti-inflammatory drugs (NSAIDs) like Advil and Motrin (ibuprofen) or Aleve (naproxen) that can harm your kidneys. Limiting your alcohol intake can also help.

Most importantly, see your healthcare provider regularly to monitor your kidney function with routine blood and urine tests and renal ultrasound. With appropriate care, CKD—a disease that affects 15% of the U.S. population, or roughly 37 million people—may never progress to the point of failure.

Summary

Uremia is a buildup of urea and other waste products in the blood caused by kidney failure. Symptoms include nausea, vomiting, sleepiness, loss of appetite, difficulty concentrating, itchiness, and fatigue.

If left untreated, uremia can cause anemia, abnormal heart rhythms, bone disease, seizures, heart failure, and coma. Treatments include dialysis and kidney transplants. Without treatment, uremia is fatal.