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Uremic Encephalopathy - Causes, Symptoms, Diagnosis, and Treatment

Published on Aug 24, 2022 and last reviewed on Mar 28, 2023   -  5 min read


Uremic encephalopathy is an abnormality of the central nervous system caused by the retention of uremic solutes. For more information, please read the article.

What Is Encephalopathy?

Encephalopathy is a condition or disease that affects the brain's normal functioning caused by viral infections, tumors, stroke, or toxins in the blood. It is a broad term that includes any brain disease that affects the normal functioning of the brain. These changes occurring inside the brain due to several health problems can lead to an altered mental state, causing confusion. an Encephalopathy is a group of disorders caused by several factors. It can cause temporary or permanent damage if left untreated.

Encephalopathy can be divided into two types-reversible and irreversible. Causes of reversible encephalopathy include metabolic encephalopathy (kidney failure, heart failure, and diabetes), infections (brain and urinary tract infections), hepatic encephalopathy (cirrhosis), and brain tumors, long-term exposure to toxins. Causes of irreversible encephalopathy include chronic traumatic encephalopathy and hypoxic-ischaemic encephalopathy. The common symptoms of encephalopathy are memory loss, confusion, trouble in making a decision, personality changes, trouble speaking and swallowing, seizures, tremors, and muscle weakness.

What Is Uremic Encephalopathy?

Uremic encephalopathy is progressive dysfunction of the brain caused by the accumulation of toxins as a result of kidney impairment. It occurs when there is an accumulation of neurotoxins inside the body. These neurotoxins are called uremic toxins. Uremic toxins include compounds such as urea, indoxyl sulfate, guanine compounds, indolic acid, phenols, and lanthionine. It is partially reversible when the kidney function becomes normal. In order to correct the kidney function, dialysis or a kidney transplant can be done. Uremic toxins are found to be responsible for causing uremic encephalopathy.

What Are the Causes of Uremic Encephalopathy?

  • Retention of Uremic Solutes - The uremic solutes or uremic toxins are the products found in the blood as a result of acute or chronic kidney failure. These compounds have a direct or cumulative effect on the biological functioning of the body.

  • Alterations in Hormonal Metabolism - An increase in the level of parathyroid hormone (hyperparathyroidism) causes an increase in the calcium content of the brain cells. Encephalopathy, however, improves with dialysis and does not affect parathyroid hormone levels. This can be used to differentiate between the effects produced by kidney impairment and hyperparathyroidism.

  • Changes in Electrolyte and Acid-Base Homeostasis - Chronic and acute kidney failure can cause an imbalance in the acid-base mechanism and fail to have homeostasis, which can directly or indirectly cause encephalopathy.

  • Imbalance in the Inhibitory and Excitatory Neurotransmitters - An increase in glycine levels in plasma and cerebrospinal fluid leads to the accumulation of guanine compounds. A decrease in glutamine and gamma-aminobutyric acid (GABA) causes activation of excitatory and N-methyl D-aspartate receptors and inhibition of inhibitory GABA receptors.

  • Oxidative Stress - Oxidative stress causes dysfunctional mitochondria to produce more uremic toxins. These alter the ability of the brain to utilize ATP-requiring pathways compared to the normal brain.

What Are Uremic Toxins?

Uremic toxins are organic or inorganic compounds that accumulate in the body due to acute or impairment in kidney function. Uremic toxins or uremic retention solutes can be divided as- small and water-soluble compounds such as urea and creatinine. Medium-sized compounds, mainly peptides. Protein-bound compounds like phenol and indoles. Other uremic toxins found are xanthosine, inosine, pseudouridine, dimethylamine, ethylamine, trimethylamine, dimethylglycine, Interleukin, tumor necrosis factor-alpha, neopterin, sorbitol, phenol, leptin, and insulin-like growth factor-1.

What Are the Signs and Symptoms of Uremic Encephalopathy?

  • Mild Symptoms - These include lassitude (lack of energy) or fatigue.

  • Seizures - Sudden and controlled electrical disturbances in the brain causing loss of consciousness, followed by confusion and uncontrollable muscle spasms, drooling at the mouth, falling, and clenching the teeth.

  • Anorexia - An eating disorder with normally low body weight.

  • Vascular Damage - Accumulation of the urine makes toxins that can contribute to amplifying vascular damage.

  • Stroke - The imbalance in the acid-base mechanism and accumulation of neurotoxins can contribute to the pathogenesis of stroke or heart attack.

  • Cognitive Dysfunction - It can be caused by several factors such as injury to the brain's vascular system, endothelial inflammation, or as a direct effect of the toxins in the blood.

  • Convulsions - Convulsions were increased in pediatric patients with increased blood urea nitrogen levels.

  • Coma - Prolonged state of unconsciousness.

  • Death - Delay in diagnosing and treating the disease can finally lead to coma and death.

Other symptoms include -

  • Disorientation.

  • Confusion.

  • Vomiting.

  • Emotional volatility.

  • Dementia.

How to Diagnose Uremic Encephalopathy?

  • Laboratory Findings - Laboratory findings such as complete blood count, comprehensive metabolic panel, magnesium level, phosphorus level, lactic acid level, and creatinine level can be screened. There is no specific test to confirm or diagnose uremic encephalopathy.

  • Imaging Tests -

    • Magnetic Resonance Imaging (MRI) - MRI can be used to study the widespread involvement of abnormalities in the cortex and subcortical white matter, basal ganglia, and hippocampus.

    • Computed Tomography (CT) - The CT scan of the brain can exclude the focal lesions in the brain, so an MRI scan is used in the studies of uremic encephalopathy.

How to Treat Uremic Encephalopathy?

Uremic encephalopathy increases the risk of morbidity and mortality in patients suffering from chronic kidney disease. It is an absolute indication to start renal replacement therapy. There is no test present to confirm uremic encephalopathy, which leads to a delay in its diagnosis. The condition can be treated either by dialysis or kidney replacement therapy. The uremic toxins can be removed by dialysis.

  • Hemodialysis - Small-sized water-soluble compounds like urea and creatinine can be easily removed by hemodialysis.

  • Dialectic Membranes - Medium-sized compounds containing peptides can only be removed by dialectic membranes with large pores. The protein-bound compounds which are produced by the metabolism of amino acids in the diet, including phenols and indoles, are widely excreted through tubular secretion of the kidneys. Removal by dialysis is limited only to the unbound compounds.

  • Management of Chronic Kidney Disease - Management of chronic kidney disease should be done simultaneously with dialysis. It can be done by using erythropoiesis-stimulating agents, calcium replacement, nutrition modification, and phosphate binders.


All the uremic substances play a negative role in causing many signs and symptoms in patients already suf fering from chronic kidney disease or acute kidney disease. Protein-bound compounds are difficult to remove from the body even after dialysis. Low molecular weight compounds can bind to protein, mainly albumin, and prevent effective removal via dialysis. Intermittent hemodialysis is found to be more effective clinically than continuous ambulatory peritoneal dialysis (CAPD). Clinical improvements in uremic encephalopathy have been found with renal replacement therapy.

Frequently Asked Questions


What Is the Impact of Uremia on the Brain?

The accumulation of uremic toxins can cause stroke and vascular damage leading to dementia and cognitive disorders. However, the early symptoms include nausea, restlessness, drowsiness, decreased concentration, and impaired cognitive functions. Eventually, the person may become disoriented, confused, and emotionally unstable.


Is It Possible to Cure Uremic Encephalopathy?

Uremic encephalopathy is a metabolic disorder that requires dialysis or renal replacement therapy to improve renal functions. Neurological symptoms can also be reversed in the case of acute and subacute episodes. For example, seizures can be treated with anticonvulsants, but cognitive functions are found to be permanent in severe cases.


How Long Does It Take for Uremic Encephalopathy to Heal?

The process of recovery from uremic encephalopathy may take a few days to weeks. However, it takes several months to identify changes in the electroencephalogram. In addition, some cognitive functions remain irreversible. That is why rapid resolution therapy is recommended during the early stages of encephalopathy. 


What Are the Four Stages of Encephalopathy?

The four stages of encephalopathy are as follows.
Stage 1: Mild confusion, sleep disturbance, decreased attention, agitation, and irritability.  
Stage 2: Lethargy, drowsiness, disorientation, and inappropriate behavior.
Stage 3: Aggressive behavior, slurred speech, and confusion. Stage 4: Coma.


Is Encephalopathy Fatal?

The severe cases of encephalopathy can be treated by renal transplantation or dialysis. However, there are permanent structural changes and damage to the brain, which may lead to death. The common reason for death due to encephalopathy is the swelling of the brain, which in turn increases the intracranial and brainstem pressure, which controls the vital functions of the body, leading to death. 


How Long Can You Survive With Uremia?

Uremia is a chronic kidney disease that can cause serious health problems. It may be fatal if the person with kidney failure does not get treated. Thus the stages of uremia have to be monitored to save the person. Studies reveal that providing treatment can save at least 70 % of individuals.


Which Are the Organs Affected by Uremia?

All body organs and systems are affected by uremia. They can cause arteriosclerosis, decreased diastolic compliance, pericarditis, hypertension or hypotension affecting the cardiovascular system, impaired cognitive functions in the central nervous system, and kidney failure affecting the excretory system. 


How Does Encephalopathy Develop?

Encephalopathy is a temporary permanent condition that alters the structure and functions of the brain. They may develop due to physical injury, toxins, lack of oxygen, high blood pressure, vitamin B1 deficiency, and inherited conditions.


Does a CT Scan Detect Encephalopathy?

A CT (computed tomography) scan uses X-rays to visualize the bones, internal organs, blood flow, and abnormalities. They can be used to diagnose encephalopathy by showing the structural and functional defects in the brain. In addition, physical examinations such as mental status tests, memory tests, coordination tests, and MRI (magnetic resonance imaging) scans are also carried out to detect encephalopathy.


Does an MRI Reveal Encephalopathy?

The causes of encephalopathy may be autoimmune, metabolic, or intoxication. MRI (magnetic resonance imaging) scans which use a magnetic field and radio waves to produce images of the organs, can identify the underlying pathology by recognizing the patterns and topographic distribution.


Can Encephalopathy Result From Dehydration?

Encephalopathy due to dehydration, called dehydration encephalopathy, commonly occurs in older individuals where the total body water is less and a sense of thirst is lost. They may present with disturbed consciousness. It is considered a neurological emergency by physicians.


Does Alcohol Consumption Lead to Encephalopathy?

The type of encephalopathy caused due to excessive alcohol consumption is called Wernicke’s encephalopathy or Wernicke-Korsakoff syndrome. It can lead to permanent brain damage if not treated and hence considered a medical emergency. The affected individuals have symptoms similar to dementia.

Last reviewed at:
28 Mar 2023  -  5 min read




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