eMedicine Specialties > Nephrology > Chronic Kidney Disease
Encephalopathy, Uremic
Updated: May 8, 2007
Introduction
Background
Uremic encephalopathy is an organic brain disorder. It develops in patients with acute or chronic renal failure, usually when creatinine clearance (CrCl) levels fall and remain below 15 mL/min.
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 renal failure. Prompt identification of uremia as the cause of encephalopathy is essential because symptoms are readily reversible following initiation of dialysis.
Pathophysiology
Uremic encephalopathy has a complex pathophysiology, and many toxins that accumulate in renal failure may be contributive. Parathyroid hormone (PTH) likely contributes to uremic encephalopathy.
Secondary hyperparathyroidism, which occurs in renal failure, causes an increase in calcium content in the cerebral cortex. In animal models with uremia, 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 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.
Numerous other uremic toxins may contribute to uremic encephalopathy, but the lack of research in this area in recent years is notable. Although the encephalopathy correlates roughly with BUN level, urea itself is not thought to be causative.
Frequency
United States
Most patients with a CrCl level less than 10% of normal probably 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.
Mortality/Morbidity
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 renal failure. 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.
Race
No racial predilection exists.
Sex
No significant association between sex and incidence exists.
Age
Uremic encephalopathy may develop at any age.
Clinical
History
- Early symptoms
- Anorexia
- Nausea
- Restlessness
- Drowsiness
- Diminished ability to concentrate
- Slowed cognitive functions
- More severe symptoms
- Vomiting
- Emotional volatility
- Decreased cognitive function
- Disorientation
- Confusion
- Bizarre behavior
- As uremic encephalopathy progresses, patients may develop myoclonus, asterixis, seizures, stupor, and coma.
Physical
- Altered mental status (confusion)
- Cranial nerve signs (nystagmus)
- Papilledema
- Hyperreflexia, clonus, asterixis
- Stupor
- Coma occurs only if uremia remains untreated and progresses.
Causes
Uremic encephalopathy may occur in a patient affected with acute or chronic renal failure of any etiology.
More on Encephalopathy, Uremic |
 Overview: Encephalopathy, Uremic |
| Differential Diagnoses & Workup: Encephalopathy, Uremic |
| Treatment & Medication: Encephalopathy, Uremic |
| Follow-up: Encephalopathy, Uremic |
| References |
| Next Page » |
References
Biasioli S, D'Andrea G, Feriani M, Chiaramonte S, Fabris A, Ronco C, et al. Uremic encephalopathy: an updating. Clin Nephrol. Feb 1986;25(2):57-63. [Medline].
Biasioli S. Neurologic aspects of dialysis. In: Nissenson A, Fine R, eds. Clinical Dialysis. 2005:855-876.
Bolton CF, Young GB. Encephalopathy of chronic renal failure. In: Neurological Complications of Renal Disease. 1990:49-74.
Brouns R, De Deyn PP. Neurological complications in renal failure: a review. Clin Neurol Neurosurg. Dec 2004;107(1):1-16. [Medline].
Deguchi T, Isozaki K, Yousuke K, Terasaki T, Otagiri M. Involvement of organic anion transporters in the efflux of uremic toxins across the blood-brain barrier. J Neurochem. Feb 2006;96(4):1051-9. [Medline].
Fraser CL, Arieff AI. Nervous system manifestations of renal failure. In: Schrier RW, ed. Diseases of the Kidney. 2001:2769-2794.
Moe SM, Sprague SM. Uremic encephalopathy. Clin Nephrol. Oct 1994;42(4):251-6. [Medline].
Further Reading
Keywords
uremia, organic brain disorders, acute renal failure, end-stage renal disease, ESRD, dialysis, hyperparathyroidism, parathyroidectomy
