Uremic Encephalopathy
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Uremic encephalopathy is an organic brain disorder. It develops in patients with acute or chronic renal failure, usually when the estimated glomerular filtration rate (eGFR) falls and remains below 15 mL/min. [1, 2, 3, 4]
Manifestations of this syndrome vary from mild symptoms (eg, lassitude, fatigue) to severe signs (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. Uremic encephalopathy may occur in a patient with acute kidney injury or chronic kidney failure of any etiology.
One contributing factor to uremic encephalopathy may involve 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. 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, 7, 8] In addition, alterations occur in metabolism of dopamine and serotonin in the brain, which may lead to early symptoms (eg, sensorial clouding).
Parathyroid hormone (PTH) likely contributes to uremic encephalopathy. [9] 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 involve 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.
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. [10]
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.
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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. [11]
Symptoms include somnolence and decreased mentation. Asterixis may be 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 end-stage renal disease (ESRD). 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.
No racial predilection exists. No significant association between sex and incidence exists. Uremic encephalopathy may develop at any age.
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Kim DM, Lee IH, Song CJ. Uremic Encephalopathy: MR Imaging Findings and Clinical Correlation. AJNR Am J Neuroradiol. 2016 Sep. 37 (9):1604-9. [Medline].
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James W Lohr, MD Professor, Department of Internal Medicine, Division of Nephrology, Fellowship Program Director, University of Buffalo State University of New York School of Medicine and Biomedical Sciences
James W Lohr, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Society of Nephrology, Central Society for Clinical and Translational Research
Disclosure: Received research grant from: GSK<br/>Partner received salary from Alexion for employment.
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Ajay K Singh, MB, MRCP, MBA Associate Professor of Medicine, Harvard Medical School; Director of Dialysis, Renal Division, Brigham and Women’s Hospital; Director, Brigham/Falkner Dialysis Unit, Faulkner Hospital
Disclosure: Nothing to disclose.
Vecihi Batuman, MD, FASN Huberwald Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Renal Section, Southeast Louisiana Veterans Health Care System
Vecihi Batuman, MD, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, International Society of Nephrology, Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.
Donald A Feinfeld, MD, FACP, FASN Consulting Staff, Division of Nephrology and Hypertension, Beth Israel Medical Center
Disclosure: Nothing to disclose.
Uremic Encephalopathy
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