Uremia

What is Uremia?

Uremia is a health condition that occurs when kidney function starts to decline. This can lead to complications like an excess of fluid in the body, imbalances of the body’s salts (electrolytes), issues with metabolism, and changes to the body’s normal functions. The word ‘uremia’ literally means ‘urine in the blood’. This condition is most commonly seen in people with chronic or advanced stage kidney disease. Less commonly, it can also occur in acute kidney injury if kidney function quickly deteriorates. Too much urea, a waste product in the blood, can harm various tissues, especially the nervous system.

Usually, over 100 uremic toxins can act as markers for this condition, present in the bloodstream at differing levels. These substances are often substances produced by the body (metabolites) that cannot be removed properly due to the impaired function of the kidneys. In addition to urea, other potentially harmful toxins can build up including parathyroid hormone, α-macroglobulin, advanced glycosylation end products, indoxyl sulfate, homocysteine, uric acid, and β-2 microglobulin. Not just a single toxic build up, but a mix of many toxins can cause the symptoms and physiological changes seen in uremia.

Urea, as well as other uremic toxins that build up due to impaired kidney clearance, can harm various tissues, especially the nervous system. This can lead to symptoms such as feeling sick, throwing up, tiredness, loss of appetite, muscle cramps, itching, and changes in mental function. These symptoms can significantly reduce a person’s quality of life and, if not treated, can cause life-threatening complications. These symptoms usually develop over time. Due to the common occurrence of changes in mental status in patients, healthcare workers have to quickly recognize these signs to start the right treatment and refer the patient for a potential kidney transplant.

Furthermore, healthcare givers need to guide and organize necessary care for patients who need renal replacement therapy (a treatment for advanced kidney failure) to ensure they get healthier. They also need to constantly check for any signs of uremia to avoid associated complications. Getting referred early to a transplant center is linked to improved survival rates and reduced life-threatening complications in uremia patients.

What Causes Uremia?

Uremia is a medical condition that can be caused by a variety of illnesses, including diseases of the kidneys and other systemic conditions that harm the kidneys. Some of these include IgA nephropathy, a kidney disorder caused by deposits of a certain type of protein; focal segmental glomerulosclerosis, a disease that damages the kidney’s filtering system; membranoproliferative glomerulonephritis, a syndrome that affects the smallest filtering units in your kidneys; and polycystic kidney disease, a genetic disorder that leads to the formation of many fluid-filled cysts in the kidneys.

Systemic conditions that may lead to uremia include common diseases like diabetes and autoimmune diseases like lupus. Other conditions include multiple myeloma, a cancer of plasma cells; amyloidosis, a condition where abnormal proteins build up in organs; several blood and immune system diseases; as well as some kidney conditions.

In the US, diabetes is the most common reason for end-stage renal disease (ESRD), and is responsible for 40% of new dialysis patients. Other factors leading up the line are high blood pressure, different types of glomerulonephritis, diseases of the tissues within and in between the kidneys, bladder infections, and tumors. Around the world, although diabetes still remains a major cause of kidney failure, glomerulonephritis is a leading cause in developing countries.

Uremia can also develop when there’s a sudden acute kidney injury that results in increased levels of urea or creatinine, which are waste products normally eliminated by the kidneys. Uremia is likely caused when the body retains a variety of harmful chemicals that could potentially work together to cause symptoms. Many different toxins have been linked to uremic symptoms, each varying in how they dissolve in water or bind to proteins, as well as their sizes. Furthermore, certain compounds that usually help control inflammation and blood vessel widening, such as glutathione and arginine, have been found to be lower in instances of kidney failure. This could also contribute to the features of uremia.

Risk Factors and Frequency for Uremia

It’s challenging to understand the exact number of uremia cases in the United States because individuals with End-Stage Renal Disease (ESRD) often start dialysis even before they show symptoms related to uremia. These symptoms usually show up when the creatinine clearance level falls below 10 or 15 mL per minute, particularly in diabetic patients. As per 2009 data from the United States Renal Data System (USRDS), annual reported incidence and prevalence of advanced chronic kidney disease (CKD) were 354 and 1665 per million people, respectively. That very year, 116,395 individuals began renal replacement therapy which led to 371 incidences per million.

The number of people with ESRD has been rising since people with this condition are living longer now. Those with diabetes or cardiovascular disease are living longer due to better survival rates and better access to kidney treatment, which has resulted in an increased incidence of ESRD in individuals aged 75 or more. On the other hand, ESRD cases in individuals aged 60 or less are falling, except for Black or Native American patients with diabetic ESRD. It’s noteworthy that only five countries, namely the United States, Japan, Brazil, Germany, and Italy account for 58% of ESRD patients worldwide, with Japan topping the list followed by Taiwan.

About 59.8% of ESRD patients are White, 33.2% are Black, 3.6% are Asian, and 1.6% are Native American. The incidence of ESRD is 3.7 times higher in Black individuals and 1.8 times higher in Native Americans compared to Whites. Minority groups tend to start dialysis later when their kidneys have extensively declined. It’s not clear whether race or ethnicity affects the likelihood of developing uremia symptoms.

Men are 1.2 times more likely to develop ESRD compared to women. However, women are 1.7 times more likely to start dialysis later than men. Moreover, women tend to develop uremia symptoms at lower creatinine levels because they have lesser muscle mass and lower baseline serum creatinine levels.

Signs and Symptoms of Uremia

Uremia is a condition that usually happens when the creatinine clearance (a mechanism to remove waste product from the body) is significantly reduced. However, in cases of sudden kidney failure, some people might experience symptoms even if clearance rates are higher than the usual threshold. Uremia symptoms can vary considerably and might include feeling sick, throwing up, feeling tired, losing appetite, losing weight, having a foul taste in the mouth, and experiencing changes in mental status, like confusion or memory loss. Often, patients might not notice slower neurological symptom onset, like forgetfulness. It’s important for doctors to ask detailed questions and possibly consult with family members or caregivers to get a clear patient history. The body’s metabolic changes, triggered by uremia, can cause certain effects, like fatigue due to anemia. Young children might show non-specific symptoms which makes a diagnosis harder.

Different health problems can be caused by an accumulation of uremic toxins and the calcification process related to uremia and end-stage kidney disease. These include high blood pressure, heart conditions, and atherosclerosis—a disease where plaque builds up inside your arteries. If not treated early, such conditions could lead to uremic symptoms. Occult gastrointestinal bleeding, a condition where minor bleeding happens in the digestive tract, could occur due to platelet issues (platelets are tiny blood cells that help your body form clots to stop bleeding) and this could cause the patient to feel nauseous or throw up.

Uremia can have a significant influence on the nervous system, possibly leading to a condition called uremic encephalopathy. This could demonstrate in fatigue, feeling tired all the time, an inability to think clearly, memory problems, experiencing seizures or falling into unconsciousness. People might also have muscle weakness, restless legs, headaches, coil a hand involuntarily, nerve inflammation, heightened reflexes, involuntary muscle twitching, and muscle cramps. Deposits of amyloid—a protein that the body makes—could lead to carpal tunnel syndrome (CTS), neuropathy, or other conditions where a nerve is pressed or trapped. Skin changes, changes in hair, nails, and the mouth’s inner surface are also common.

Doctors examining someone with uremia will look for signs related to anemia, fluid retention, and acidemia (a condition where your body fluids contain too much acid). Severe malnutrition could lead to muscle wasting while disturbances in electrolyte balance could lead to muscle cramping, changes in mental status, and irregular heart rhythms. Doctors also commonly look for and might find the following:

Uremic frost (a whitish deposit of urea crystals on the skin)
Uremic fetor (breath smelling like urine)
Gum changes, small red or purple spots caused by bleeding into the skin, changes in tooth enamel, or bleeding gums
Murmur due to inflammation of the pericardium—an outer layer of the heart
Lung fluid overload
Swelling in extremities
High blood pressure to the point of being dangerous
Facial swelling
Asterixis—a movement disorder
Papilledema—swelling in the optic nerve at the back of the eye

Testing for Uremia

Diagnosing kidney failure often depends on irregularities in your glomerular filtration rate (GFR) or the ability of your kidneys to clear creatinine, a waste product, from your blood. It’s very important to determine whether kidney failure is acute, meaning sudden, or chronic, meaning it’s been developing over a long period, as acute kidney injury might be reversible.

Various lab tests help identify the cause underlying symptoms associated with uremia (a high level of waste products in the blood due to kidney failure). These include tests for hemoglobin, calcium, phosphate, parathyroid hormone, albumin, potassium, and bicarbonate levels. Tests also include urinalysis, a test that checks for different cells and substances in your urine.

Collecting urine over a 24-hour period can give deeper insights into GFR and creatinine clearance, but this method could be burdensome and may yield inaccurate results if not collected properly. There’s also an option for a nuclear medicine test that directly measures the GFR, but this test is inconvenient and costly compared to commonly used formulas, such as the Cockcroft-Gault or the Modification of Diet in Renal Disease formulas.

Chronic kidney disease (CKD) is categorized into stages based on GFR, which is calculated using the Modification of Diet in Renal Disease formula, according to the National Kidney Foundation.

– Stage 1: Normal GFR (90 mL/min or greater)
– Stage 2: Slightly reduced GFR (60-90 mL/min)
– Stage 3a: Moderately reduced GFR (45-59 mL/min)
– Stage 3b: Moderate to severely reduced GFR (30-44 mL/min)
– Stage 4: Severely reduced GFR (15-29 mL/min)
– Stage 5: End-Stage Renal Disease (ESRD) (GFR <15 mL/min or patient is on dialysis) A renal ultrasound is used to assess the size and shape of the kidneys and can potentially reveal indications of enlarged kidneys, hydronephrosis (swelling of a kidney due to a build-up of urine), and obstructions in the ureter or bladder. Smaller, echogenic kidneys suggest more prolonged, irreversible changes resulting from long-standing kidney disease. Patients with uremia due to urinary obstruction should be treated to relieve the obstruction, and the cause should be identified to establish a long-term treatment plan. A test that measures protein in the urine is beneficial in diagnosing conditions that can lead to End-Stage Renal Disease (ESRD). Monitoring changes in proteinuria over two years can help predict the risk of ESRD. In patients with a significant change in mental status, a brain computed tomography (CT) scan might be necessary. Additionally, if there's any suspicion of brain or abdominal injury caused by falls or trauma, a CT scan might be required. An abdominal CT scan can also help understand the cause of kidney enlargement if observed on ultrasound. Magnetic resonance imaging (MRI) can be useful for evaluating problems with the renal artery or dissection, which are potentially reversible causes of renal failure. A renal biopsy, a procedure that involves taking a small sample of kidney tissue for testing, could be crucial in identifying treatable causes of kidney injuries. However, if the kidneys are small, a biopsy is usually avoided due to risks like bleeding and less likelihood of finding a treatable condition.

Treatment Options for Uremia

If a patient is showing symptoms of uremia – feeling sick, vomiting, unmanageable levels of potassium in the blood, or metabolic acidosis (a chemical imbalance in the body) – that cannot be controlled by medicine, they may be recommended for dialysis. Dialysis is a procedure that filters and cleans the blood, like healthy kidneys would do.
They may also need immediate dialysis if they are suffering from extreme cases of uremia, such as an excessive amount of potassium in the body, metabolic acidosis, fluid buildup around the heart, or uremic encephalopathy (a type of brain disorder caused by kidney failure).

For those with kidney issues, getting a kidney transplant can greatly improve their life quality and survival rate compared to dialysis. While long-term dialysis treatments can be used as a temporary solution for people awaiting transplants or those who are not fit for the transplant operation, it is crucial to consider the transplant option early. The waiting list for a transplant can often be more than 2 to 3 years, so it’s recommended to consider getting on the waitlist when kidney function starts to decline.

For those requiring dialysis, preparations such as securing access for the procedure should commence months before. It is important to note that the decision to start dialysis is typically made based on the patient’s symptoms rather than just the results of kidney function tests (GFR levels). The most common reason for starting dialysis is uremia, so doctors need to be aware of its signs.

To help manage anemia (a lack of red blood cells) in people with kidney disease, iron may be given. This can be given during dialysis sessions or through oral or intravenous (IV) therapy if dialysis has not yet begun. It’s also possible for specific medications to be given when the hemoglobin levels (a protein in your red blood cells that carries oxygen) drop below 10 g/dL.

Hyperparathyroidism (overactive parathyroid glands), along with related calcium and phosphorus imbalances in the blood, can be treated with various medications. This includes oral calcium supplements, oral vitamin D therapy, and oral medications that bind with phosphorus in the gut. It’s typically necessary for people with chronic kidney disease and end-stage renal disease (ESRD) to take calcitriol, a type of vitamin D that can be absorbed by the body.

A dietitian can offer advice when considering changes to a diet. People with chronic kidney disease should follow a diet low in potassium and phosphorus, while keeping salt intake restricted to 2 to 3 grams. There is a debate on protein intake. Current recommendations include a low-protein diet with 0.8 to 1 gram of protein per kilogram of body weight daily, with an additional gram of protein for every gram lost in urine for patients with a large amount of protein in the urine.

Research shows that a low-protein diet helps slow the progression of chronic kidney disease. Though it’s valid to worry about the risk of malnutrition, close nutritional monitoring and supplementation, as necessary, can meet all nutritional needs on a low-protein diet. There’s also significant evidence indicating that eating a plant-based diet can slow the progression of chronic kidney disease and delay the need for dialysis. Consuming animal protein can contribute to uremia by raising nitrogen waste levels, leading to increased pressure in the kidneys and greater filtration within the kidneys.

Patients with a creatinine clearance (a measure of kidney function) of less than 20 mL/min should be cautious about their potassium intake and the use of certain medications (like diuretics that spare potassium, ACE inhibitors, blockers of angiotensin receptors, beta-blockers, and nonsteroidal anti-inflammatory drugs). In addition, the prescription of anticoagulants (blood-thinning medicines) or antiplatelet medications (drugs that prevent blood clots) requires careful consideration and monitoring due to hazards associated with these drugs in people with end-stage renal disease. Medications that can harm the kidneys like nonsteroidal anti-inflammatory drugs and certain types of antibiotics should be avoided by all people with kidney disease. The administration of N-acetylcysteine (a medication to prevent or lessen kidney damage) before IV contrast for radiologic imaging may help reduce the risk of kidney damage. However, considering alternative imaging techniques like MRI is advisable for these patients to prevent the risk of acute kidney injury.

Uremia, a condition characterized by high waste product levels in the blood due to kidney dysfunction, is often easily identified through medical tests that check kidney function. But it’s important to note that other medical conditions can show similar symptoms. For example:

A brain condition called hepatic encephalopathy, which results from high levels of ammonia in the blood, can cause hand flapping tremors and changes in mental state much like uremia.
Liver failure can lead to lower albumin levels in the blood, mimicking the symptoms of a kidney disease called nephrotic syndrome.
Congestive heart failure can cause fluid in the lungs and swelling, similar to the signs of uremia.
Pericarditis, inflammation of the heart’s protective layers, can cause sound patterns when the heart beats that are similar to those seen in uremic pericarditis.

Additionally, using certain substances can cause changes in mental state, and people with kidney failure may not be able to cleanse these substances from their bodies as well. Too much magnesium or calcium in the blood is another factor that could change a person’s mental state.

With these conditions sharing similar signs and symptoms, diagnosing uremia usually involves basic laboratory tests and a thorough review of the symptoms to distinguish between these various conditions.

What to expect with Uremia

The chances of recovering from acute kidney injury or kidney failure caused by reversible factors such as lupus nephritis (a kidney disease caused by lupus), anti-glomerular basement membrane disease (a rare kidney disease), granulomatosis with polyangiitis (a rare condition causing inflammation of blood vessels), thrombotic thrombocytopenic purpura (a disorder causing blood clots in small blood vessels), multiple myeloma (a cancer of plasma cells), and hemolytic-uremic syndrome (a condition causing destruction of blood vessels), are greatly improved with early detection and swift start of treatment.

Without intervention, the outlook for those suffering from uremia, which is a high level of waste products in the blood because kidneys are not functioning properly, is generally not good. However, with the use of dialysis (a process to remove waste and excess water from the blood) or kidney transplantation, the outlook significantly improves. Regular check-ups are necessary as many patients experience complications during treatment.

While death rates have declined over the past thirty years, those with kidney failure still have a higher risk of death compared to the average person, particularly in the initial months after beginning dialysis.

Possible Complications When Diagnosed with Uremia

Uremia, a high level of waste products in your blood, can lead to many complications. Some of these might include changes in your skin color, intense itching, inflammation of the sac-like covering around your heart, build-up of fluid around your heart, fluid in your lungs, heart valve hardening, brain dysfunction, imbalance of bodily salts, heart disease, and inflammation of the pancreas associated with uremia.

Complications of Uremia:

Skin changes, such as darker color
Intense itching
Inflammation of the sac-like covering around the heart
Fluid build-up around the heart
Fluid in the lungs
Heart valve hardening
Brain dysfunction related to uremia
Imbalance of bodily salts
Heart disease
Inflammation of the pancreas associated with uremia

Preventing Uremia

Patients should avoid medications that can hurt the kidneys, such as aminoglycoside antibiotics (a type of antibiotic), NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) and other substances that can harm the kidneys. If a patient requires an X-ray that involves using a special dye (IV contrast), taking a supplement called N-acetyl-cysteine before and after the test can help protect your kidneys. Healthcare providers should think about using other methods like ultrasound or MRI that are safer for the kidneys, especially for patients who have diabetes.

Patients should be informed about the importance of a diet that is low in salt, phosphorus, and potassium. In addition to this, adding prebiotics, synbiotics, probiotics, and laxatives in their diet may help reduce the generation of harmful substances in the body. Research has shown that a diet low in protein, especially a diet based on plants, can effectively slow the worsening of Chronic Kidney Disease (CKD) and delay the need for dialysis. It is extremely important to consult with a dietitian when possible, as patients with CKD often have complex dietary needs.

Patients should be taught about three major treatments for severe kidney disease, which are peritoneal dialysis (a treatment that uses the lining of your abdomen to filter your blood), hemodialysis (a treatment where a machine filters your blood) and kidney transplants, when their kidney disease reaches stage 4. Getting in touch with a transplant center early can help plan a kidney transplant ahead of time, which can lead to better patient outcomes. Just like that, early planning for dialysis can also help manage kidney disease better.

Frequently asked questions

The prognosis for uremia is generally not good without intervention. However, with the use of dialysis or kidney transplantation, the outlook significantly improves. Regular check-ups are necessary as many patients experience complications during treatment. While death rates have declined over the past thirty years, those with kidney failure still have a higher risk of death compared to the average person, particularly in the initial months after beginning dialysis.

Uremia can be caused by a variety of illnesses, including diseases of the kidneys and other systemic conditions that harm the kidneys. Some specific causes include IgA nephropathy, focal segmental glomerulosclerosis, membranoproliferative glomerulonephritis, and polycystic kidney disease. Systemic conditions like diabetes and autoimmune diseases can also lead to uremia. Additionally, uremia can develop from a sudden acute kidney injury that results in increased levels of urea or creatinine.

Signs and symptoms of Uremia include: - Feeling sick - Throwing up - Feeling tired - Losing appetite - Losing weight - Having a foul taste in the mouth - Experiencing changes in mental status, like confusion or memory loss - Slow onset of neurological symptoms, like forgetfulness - Fatigue due to anemia - Non-specific symptoms in young children, making diagnosis harder - High blood pressure - Heart conditions - Atherosclerosis (plaque buildup in arteries) - Occult gastrointestinal bleeding, leading to nausea or vomiting - Uremic encephalopathy, characterized by fatigue, cognitive impairment, memory problems, seizures, and unconsciousness - Muscle weakness - Restless legs - Headaches - Involuntary hand coiling - Nerve inflammation - Heightened reflexes - Involuntary muscle twitching - Muscle cramps - Deposits of amyloid leading to carpal tunnel syndrome, neuropathy, or nerve compression - Skin changes - Changes in hair, nails, and the mouth's inner surface - Signs related to anemia, fluid retention, and acidemia - Severe malnutrition leading to muscle wasting - Disturbances in electrolyte balance leading to muscle cramping, changes in mental status, and irregular heart rhythms - Uremic frost (a whitish deposit of urea crystals on the skin) - Uremic fetor (breath smelling like urine) - Gum changes, small red or purple spots caused by bleeding into the skin, changes in tooth enamel, or bleeding gums - Murmur due to inflammation of the pericardium - Lung fluid overload - Swelling in extremities - High blood pressure to the point of being dangerous - Facial swelling - Asterixis (a movement disorder) - Papilledema (swelling in the optic nerve at the back of the eye)

The types of tests that are needed for Uremia include: - Lab tests for hemoglobin, calcium, phosphate, parathyroid hormone, albumin, potassium, and bicarbonate levels - Urinalysis to check for different cells and substances in the urine - Collecting urine over a 24-hour period to assess GFR and creatinine clearance - Nuclear medicine test to directly measure GFR - Renal ultrasound to assess the size and shape of the kidneys - Test to measure protein in the urine - Brain computed tomography (CT) scan if there are changes in mental status or suspicion of brain or abdominal injury - Abdominal CT scan to understand the cause of kidney enlargement - Magnetic resonance imaging (MRI) to evaluate problems with the renal artery or dissection - Renal biopsy to identify treatable causes of kidney injuries

A doctor needs to rule out the following conditions when diagnosing Uremia: - Hepatic encephalopathy - Liver failure - Nephrotic syndrome - Congestive heart failure - Pericarditis - Changes in mental state caused by certain substances - High levels of magnesium or calcium in the blood

The side effects when treating Uremia include: - Skin changes, such as darker color - Intense itching - Inflammation of the sac-like covering around the heart - Fluid build-up around the heart - Fluid in the lungs - Heart valve hardening - Brain dysfunction related to uremia - Imbalance of bodily salts - Heart disease - Inflammation of the pancreas associated with uremia

A nephrologist.

The text does not provide information about how common uremia is.

Uremia is treated through dialysis, which is a procedure that filters and cleans the blood, similar to what healthy kidneys would do. Dialysis is recommended for patients who are showing symptoms of uremia that cannot be controlled by medicine, or for those who are suffering from extreme cases of uremia. Immediate dialysis may be necessary for patients with excessive potassium levels, metabolic acidosis, fluid buildup around the heart, or uremic encephalopathy.

Uremia is a health condition that occurs when kidney function starts to decline, leading to complications such as excess fluid in the body, imbalances of electrolytes, issues with metabolism, and changes to normal bodily functions. It is most commonly seen in people with chronic or advanced stage kidney disease, but can also occur in acute kidney injury. Uremia is characterized by the build-up of urea and other toxins in the blood, which can harm various tissues, especially the nervous system.