What is Uremic Encephalopathy?
Uremic encephalopathy is a condition where the brain doesn’t function properly because toxins build up in the body due to severe kidney failure. This typically happens in people who have either sudden or ongoing kidney failure that reduces their kidney function to less than 15%. Symptoms of uremic encephalopathy can range from subtle to severe, and the condition tends to get worse if left untreated. However, starting treatment, such as dialysis, can often reverse some of the effects.
This syndrome probably occurs due to changes in how hormones are metabolized, a buildup of waste products usually filtered by the kidneys, changes in electrolyte and acid-base balance, alterations in how substances pass through the brain’s protective barrier, changes in blood vessel behavior, and inflammation.
Diagnosing uremic encephalopathy can be tricky because there are no specific signs, tests, or imaging results. Often, it’s diagnosed after the fact when symptoms improve following dialysis or a kidney transplant. However, if symptoms don’t improve after removing these toxins through treatment, other potential causes should be looked into.
What Causes Uremic Encephalopathy?
Uremic encephalopathy, a type of brain disorder, usually happens because of elements that increase the amount of uremic toxins in the body. This usually involves problems with the kidneys like acute kidney injury or chronic kidney disease (CKD). Uremic toxins are harmful substances that can build up in the body when the kidneys aren’t working properly.
One of the most commonly studied uremic toxins is urea, and it’s often used as a stand-in to study other uremic toxins. Severe mental changes due to uremic encephalopathy usually occur when the kidneys’ filtration rate, or eGFR, drops below 15 mL/min. However, even less severe mental changes can be detected when the eGFR is between 40 and 60 mL/min.
Typically, the buildup of uremic toxins in a person’s blood happens when they experience acute kidney injury. This could be because they can’t eliminate certain substances through kidney therapy, or because they don’t respond to therapy. There are many possible causes behind this buildup, including drugs, toxins, prolonged low blood pressure, dehydration, serious infection (sepsis), and blood loss. Uremic encephalopathy can also develop in patients with CKD when their kidney filtration rate lowers due to sudden severe issues such as infections, drugs, excessive vomiting, or diarrhea.
Patients undergoing hemodialysis, a type of kidney therapy, can also develop uremic encephalopathy if they don’t receive enough dialysis. This can be due to factors like not following treatment guidelines or problems with an arteriovenous fistula, which is a connection made between an artery and a vein in the body that helps with dialysis treatment.
Risk Factors and Frequency for Uremic Encephalopathy
Uremia is a condition that’s hard to define specifically and can cause complications in interpreting medical data. However, it’s rare for severe encephalopathy, a type of brain disease, to develop in patients with progressive Chronic Kidney Disease (CKD) because they usually receive renal replacement therapy before things get that bad. Uremic encephalopathy can also happen when acute kidney injury occurs, which involves a less predictable and faster decline in the patient’s glomerular filtration rate (GFR), the measure of functioning kidney.
Cognitive dysfunction, or problems with thinking and memory, can happen as a result of a number of factors such as vascular injury, inflammation of the blood vessel lining, or direct effects of neurotoxins, and this can affect up to 60% of patients with CKD. However, it’s not clear how neurotoxins and cognitive dysfunction are related, which makes it hard to estimate how common uremic encephalopathy is. In a study with children, they found that uremic encephalopathy was seen in 40% of patients when their blood had more than 90 mg/dL of urea nitrogen. As these levels went up, these kids were more likely to have seizures.
- Uremic encephalopathy can make CKD much worse and increase the possibility of death.
- Its symptoms can be reversed by starting dialysis and removing toxic particles in cases of acute kidney injury.
- For patients with End-Stage Renal Disease (ESRD), the condition can also be reversed with dialysis or a kidney transplant.
- Severe complications like seizures or coma can be fatal.
- Recognizing neurological symptoms early in patients with reduced kidney function is critical to prevent illness and death.
- Starting dialysis therapy promptly can help reduce death rates.
It’s important to note that there’s no bias towards any specific race, and it has nothing to do with gender when it comes to the occurrence of uremic encephalopathy. This condition can happen to anyone irrespective of their age.
Signs and Symptoms of Uremic Encephalopathy
Uremic encephalopathy is a condition that affects the brain due to advanced kidney disease, and its symptoms can vary greatly depending on how quickly the kidney disease progresses. For individuals whose kidney function, measured by eGFR, slowly gets worse, they might experience tiredness, lack of appetite, weight loss, and nausea. These patients might also show slight, gradual changes in their thinking, like being less alert or having difficulty focusing.
However, those with a rapid decrease in kidney function could have more intense symptoms of uremic encephalopathy. These might include confusion, agitation, disorientation, drastic mood changes, seizures, and in extreme cases, coma. A doctor’s examination could reveal problems with memory, judgment, and calculation abilities. They might also have unusually brisk reflexes, shaky hands, swelling of the optic nerve at the back of the eye, and uncontrolled eye movements. Additionally, damage to the nerves (neuropathy) and muscles (myopathy) might be seen.
- Tiredness
- Lack of appetite
- Weight loss
- Nausea
- Less alertness
- Difficulty focusing
- Confusion
- Agitation
- Disorientation
- Drastic mood changes
- Seizures
- Problems with memory and judgment
- Difficulties performing basic calculations
- Unusually brisk reflexes
- Shaky hands
- Swelling of the optic nerve
- Uncontrolled eye movements
- Damage to the nerves and muscles
Testing for Uremic Encephalopathy
Uremic encephalopathy is a condition that requires immediate treatment through what’s known as renal replacement therapy or dialysis. It’s a tricky condition to identify, as it can show up in different ways and there isn’t a straightforward test for it. This often means delays in catching it early on. A key part of diagnosing this condition involves ruling out other conditions that may look like uremic encephalopathy : infections, damage to the protective coating of nerves, internal bleeding in the brain, high blood pressure affecting the brain, strokes, disequilibrium syndrome (a rare condition that affects balance), and others.
There aren’t specific tests that can say for certain if someone has uremic encephalopathy. However, kidney function tests that show significantly abnormal levels of two substances – BUN and creatinine – can hint at the diagnosis. Numerous other tests need to be run quickly to rule out conditions that may look like uremic encephalopathy, especially in patients with advanced Chronic Kidney Disease (CKD). Tests can include checking for unusually high levels of white blood cells (suggesting infection), measuring levels of electrolytes and glucose (to rule out causes linked to the body’s salt and sugar levels), checking calcium, magnesium, phosphorus, and parathyroid hormone levels (as these can contribute to ‘metabolic encephalopathy’), and also looking at lactic acid levels and a toxicology screen.
There’s also something called a lumbar puncture, which won’t help in diagnosing uremic encephalopathy, but might be needed if a patient’s condition doesn’t improve even after dialysis. This test can look for other neurological conditions. And lastly, C-reactive protein can be measured to check for possible infection if there’s a clinical suspicion of it.
An electroencephalogram (EEG), a test that tracks and records brain wave patterns, can be used but won’t give a clear diagnosis. The EEG results vary in uremic encephalopathy. But, the degree to which the EEG wave activity slows down is proportional to the worsening of kidney function. After dialysis, the EEG changes stabilize but may not return to the original state. Improvement may be seen over several months.
Cognitive tests like the trail-making test (a test to measure speed of processing), the short-term memory test, and the choice reaction time test (a test to measure decision-making) can be used.
Imaging of the brain with a CT (computed tomography) scan can help rule out localized brain lesions. An MRI (magnetic resonance imaging) can show a range of brain involvement. MRI can show abnormalities in various areas of the brain which can result in a variety of symptoms. Based on MRI, patients with uremic encephalopathy can fall into three categories: those with cortical and subcortical involvement, those with bilateral basal ganglia involvement (common in diabetic patients), and those with only white matter involvement (which is rare).
Interestingly, the presence of a condition called PRES (posterior reversible leukoencephalopathy syndrome) in imaging studies may suggest a connection between issues in blood vessels and neuronal dysfunction in uremic encephalopathy. Some MRI changes may reverse after a few hemodialysis sessions compared to another kind of dialysis called continuous ambulatory peritoneal dialysis (CAPD). It’s generally understood that intermittent hemodialysis can rid the body of uremic toxins faster than CAPD, but no evidence exists currently to distinguish reversible and non-reversible changes in functional imaging.
Treatment Options for Uremic Encephalopathy
If you are suffering from uremic encephalopathy, a condition due to high levels of waste products in your blood, doctors will need to initiate a kidney treatment called renal replacement therapy. This therapy replaces the role of the kidneys in clearing waste from your body. In a study, three patients who were not producing urine and were being treated using a method known as peritoneal dialysis still developed uremic encephalopathy. However, when hemodialysis—a different type of dialysis—was initiated, their condition improved.
These patients also had low levels of proteins in their blood and signs of malnutrition, which could have been contributing to their health problems. Oftentimes, doctors start a trial of renal replacement therapy to check if symptoms improve. Meanwhile, they also manage chronic kidney disease by prescribing medicines to stimulate blood cell production, controlling phosphorus/calcium levels, replacing calcium, and suggesting dietary changes.
When treating uremic encephalopathy, doctors need to address several factors common to patients with end-stage renal disease, which is kidney failure needing dialysis or transplant:
- The adequacy of dialysis: how well it’s working to remove waste from the body.
- Correction of anemia: low levels of red blood cells that carry oxygen.
- Regulation of calcium and phosphate: maintaining a balance of these minerals which are essential for body functions.
Research suggests that intermittent hemodialysis (repeated dialysis sessions at certain intervals) clears waste more effectively than continuous ambulatory peritoneal dialysis (a home-based dialysis treatment), but it may carry the risk of triggering a consequence known as dialysis disequilibrium syndrome due to rapid changes in body fluids when dialysis starts.
Doctors can use a medication called mannitol to prevent this condition during the first few sessions of intermittent hemodialysis. In fact, studies illustrate that mannitol can lessen the changes in blood concentration by 60% and reduce symptoms in patients.
The main takeaway is that to prevent uremic encephalopathy, renal replacement therapy should be started timely. It is recommended to plan for dialysis or kidney transplant when the estimated kidney filtering rate drops below 20 mL/min. Personalized patient care is highly encouraged, by making the right choices considering patients’ individual needs and health status, as per the 2019 Kidney Disease Outcomes Quality Initiative guidelines.
What else can Uremic Encephalopathy be?
Uremic encephalopathy is a condition that doctors diagnose after ruling out other possibilities. The following conditions are also considered when diagnosing:
- Wernicke-Korsakoff encephalopathy
- Hypertensive encephalopathy
- Hyperosmolar coma
- Disequilibrium syndrome
- Metabolic encephalopathy
- Sepsis
- Fluid and electrolyte disturbances, such as low sodium levels (hyponatremia) and high magnesium levels (hypermagnesemia)
- Effects from drugs
- PRES (Posterior Reversible Encephalopathy Syndrome)
- Osmotic demyelination syndrome
- Hepatic encephalopathy
- Low blood sugar (hypoglycemia)
To help remember the set of conditions that can cause widespread brain injury as seen on an MRI, you can use the acronym “CRUMPLED.” In this term, C stands for Creutzfeldt-Jakob disease, R for reversible cerebral vasoconstriction syndrome, U for uremic encephalopathy, M for mitochondrial cytopathy/encephalopathy, P for prolonged seizure or PRES, L for liver disease, E for encephalitis/infectious, and D for diabetes mellitus causing hypoglycemia.
What to expect with Uremic Encephalopathy
Renal replacement therapy, a treatment that takes over kidney function, can typically alleviate the symptoms of uremic encephalopathy, a condition where the brain is affected due to kidney failure. However, recovery may take from a few days up to a few weeks. Changes observed in EEG (Electroencephalogram, a test used to assess the brain’s electrical activity) may take several months to recover and might not return to their initial state.
Some cognitive changes, meaning alterations in mental functions like memory and attention, could be permanent, emphasizing the need to start renal replacement therapy before uremic encephalopathy develops. This condition is generally more severe in patients experiencing acute kidney injury, which is a sudden episode of kidney failure or damage. This happens because of the damaging effects of nitrogen-rich waste products and other toxins that may affect the brain due to the impaired function of the kidneys.
Possible Complications When Diagnosed with Uremic Encephalopathy
Uremic encephalopathy, a brain disorder caused by severe kidney failure, can lead to severe complications such as seizures, falling into a coma, or even death. Starting kidney replacement therapy can help to partly reverse the effects of this condition. However, some changes in thinking abilities may become permanent.
Complications:
- Seizures
- Coma
- Potential death
Treatment:
- Renal replacement therapy, though it may only partially reverse the disorder
After-effects:
- Some cognitive changes may persist
Preventing Uremic Encephalopathy
Kidney doctors, or nephrologists, need to keep a close eye on patients who have advanced kidney disease when they are not hospitalized. It’s essential to regularly check how well your kidneys are cleaning your blood, a measure known as eGFR (estimated Glomerular Filtration Rate). This is very important to start dialysis, a treatment cleaning your blood when your kidney is unable to do so, before a condition called uremic encephalopathy develops. Uremic encephalopathy can occur when waste products accumulate in the brain due to improperly functioning kidneys.
For patients with ESRD (End-Stage Renal Disease, the last stage of chronic kidney disease), it’s important to avoid malnutrition. This can be achieved by these patients consuming a sufficient amount of protein daily (1.2 grams for every kilogram of their body weight per day). Thus, regular protein intake plays a vital role in the well-being of these patients.
