Uremic encephalopathy is an organic brain disorder. It develops in patients with acute or chronic renal failure, usually when the estimated glomerular filtration (eGFR) level falls and remains below 15 mL/min. [1, 2, 3, 4]
Manifestations of this syndrome vary from mild symptoms (eg, lassitude, fatigue) to severe symptoms (eg, seizures, coma). Severity and progression depend on the rate of decline in renal function; thus, symptoms are usually worse in patients with acute kidney injury. Prompt identification of uremia as the cause of encephalopathy is essential because symptoms are readily reversible following initiation of dialysis. [5, 6]
Uremic encephalopathy has a complex pathophysiology, and many toxins that accumulate in kidney failure may be contributive. Parathyroid hormone (PTH) likely contributes to uremic encephalopathy. 
Secondary hyperparathyroidism, which occurs in kidney failure, causes an increase in calcium content in the cerebral cortex. In animal models with uremia, electroencephalographic (EEG) changes were typical of those observed in patients with renal failure. In uremic patients with secondary hyperparathyroidism, EEG changes have been shown to improve after medical suppression of PTH or parathyroidectomy.
The specific mechanism by which PTH causes disturbance in brain function is unclear, but it may be caused by increases in intracellular concentration of calcium in brain cells. However, since the encephalopathy improves with dialysis, which does not have a marked effect on PTH levels, hyperparathyroidism is not thought to be the main cause.
Another theory about the etiology of uremic encephalopathy suggests imbalances of neurotransmitter amino acids within the brain. During the early phase of uremic encephalopathy, plasma and cerebrospinal fluid (CSF) determinations indicate that levels of glycine increase and levels of glutamine and gamma-aminobutyric acid (GABA) decrease; additionally, alterations occur in metabolism of dopamine and serotonin in the brain, which may lead to early symptoms (eg, sensorial clouding). As uremia progresses, it has been proposed that the accumulation of guanidino compounds results in activation of excitatory N-methyl-D-aspartate (NMDA) receptors and inhibition of inhibitory GABA receptors, which may cause myoclonus and seizures. [5, 8, 9]
A study of acute kidney injury in mice found evidence of a blood-brain barrier disruption from such injury, with increased neuronal pyknosis and microgliosis. In addition, proinflammatory chemokines were increased in brain tissue. 
Numerous other uremic toxins may contribute to uremic encephalopathy, but there has been a notable lack of research in this area. Although the encephalopathy correlates roughly with blood urea nitrogen (BUN) level, urea is not itself thought to be causative.
Most patients with an eGFR of less than 10 mL/min develop some degree of encephalopathy; however, they may not be clearly symptomatic. In one pediatric study, encephalopathy occurred in 40% of the children with a BUN level greater than 90 mg/dL. As the BUN level increased, the likelihood of these children developing convulsions increased. 
Symptoms include somnolence and decreased mentation. Asterixis is usually present. These findings are reversible following initiation of dialysis and recovery of renal function in patients with acute kidney injury. Symptoms are also reversible following the institution of dialysis or renal transplantation in patients with chronic renal insufficiency. The severe complications (ie, seizures, coma) can lead to death. Early recognition of encephalopathy in the setting of decreased renal function is crucial to prevent morbidity or mortality. With prompt dialytic therapy, the mortality rate is low.
Race-, Sex-, and Age-related Demographics
No racial predilection exists. No significant association between sex and incidence exists. Uremic encephalopathy may develop at any age.
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