http://emedicine.medscape.

com/article/239191-overview#a0104

Uremic Encephalopathy
Author: James W Lohr, MD; Chief Editor: Vecihi Batuman, MD, FACP, FASN

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.[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 withacute renal failure. Prompt
identification of uremia as the cause of encephalopathyis essential because symptoms are
readily reversible following initiation ofdialysis.[5, 6]

Pathophysiology
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.[7]
Secondary hyperparathyroidism, which occurs in kidney 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. Inuremic 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.[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.[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 BUN
level, urea is not itself thought to be causative.

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.
Penyebab
GGA dan CKD

Laboratory Studies

Electrolytes, BUN, creatinine, and glucose[12]

Markedly elevated BUN and creatinine levels are seen in uremic encephalopathy.
Obtain serum electrolyte and glucose measurements to rule outhyponatremia, hypernatremia,
hyperglycemia, and hyperosmolar syndromes as the cause of encephalopathy.
Obtain a complete blood cell count to detect leukocytosis, which may suggest an infectious
cause and determine whether anemia is present. (Anemia may contribute to the severity of
mental alterations.)
Obtain serum calcium, phosphate, and PTH levels to determine the presence
ofhypercalcemia, hypophosphatemia, and severe hyperparathyroidism, which cause metabolic
encephalopathy.
Serum magnesium levels may be elevated in a patient with renal insufficiency, particularly if the
patient is ingesting magnesium-containing antacids.Hypermagnesemia may manifest as
encephalopathy.
Order a toxicology screen in all patients.
Medication levels
Determine drug levels because medications may accumulate in patients with kidney failure
and contribute to encephalopathy (eg, digoxin, lithium).

Some medications cannot be detected and are excreted by the kidney. These may also
accumulate in patients with kidney failure, resulting in encephalopathy (eg, penicillin,
cimetidine, meperidine, baclofen).

Imaging Studies

Severe symptoms
Obtain an MRI or head CT scan for a uremic patient who presents with severe neurologic
symptoms to rule out structural abnormalities (eg, cerebrovascular accident, intracranial
mass).
A CT scan does not demonstrate any characteristic findings for uremic encephalopathy.
With milder symptoms, initially treat the patient with dialysis and observe for neurologic
improvement.

Other Tests

Electroencephalogram
An EEG is commonly performed on patients with metabolic encephalopathy. Findings typically
include the following: (1) slowing and loss of alpha frequency waves, (2) disorganization, and
(3) intermittent bursts of theta and delta waves with slow background activity.
Reduction in frequency of EEG waves correlates with the decrease in renal function and the
alterations in cerebral function. After the initial period of dialysis, clinical stabilization may
occur while the EEG findings do not improve. Eventually, EEG results move toward normal.
Aside from the routine EEG, evoked potentials (EPs) (ie, EEG signals that occur at a
reproducible time after the brain receives a sensory stimulus [eg, visual, auditory,
somatosensory]) may be helpful in evaluating uremic encephalopathy.
Chronic renal failure prolongs latency of the cortical visual-evoked response. Auditory-evoked
responses are generally not altered in uremia, but delays in the cortical potential of the
somatosensory-evoked response do occur.
Cognitive function tests: Several cognitive function tests are used to evaluate uremic
encephalopathy.
Uremia may result in worse performance on the trail-making test, which measures
psychomotor speed; the continuous memory test, which measures short-term recognition; and
the choice reaction time test, which measures simple decision making.
Alterations in choice reaction time appear to correlate best with renal failure.

Procedures

Lumbar puncture
Lumbar puncture is not routinely performed; however, it may be indicated to find other causes
of encephalopathy if a patient's mental status does not improve after initiation of dialysis.
No specific CSF finding indicates uremic encephalopathy.

Medical Care
No medications are specific to the treatment of encephalopathy.

The presence of uremic encephalopathy in a patient with either acute kidney failure or chronic
kidney failure is an indication for the initiation of dialytic therapy (ie, hemodialysis, peritoneal
dialysis, continuous renal replacement therapy). After beginning dialysis, the patient generally
improves clinically, although EEG findings may not improve immediately.
In patients with end-stage renal disease (ESRD), EEG abnormalities generally improve after
several months but may not completely normalize.
Address the following factors when treating uremic encephalopathy, which are also included in
the standard care of any patient with ESRD:

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Adequacy of dialysis
Correction of anemia
Regulation of calcium and phosphate metabolism

Consultations

Consult a neurologist if symptoms do not improve upon initiation of dialysis therapy.

Consult a vascular surgeon for placement of vascular access in patients with ESRD.
Refer patients with ESRD to a dietitian familiar with renal diseases.

Diet

To avoid malnutrition in patients with ESRD, maintain adequate protein intake (>1 g/kg/d) and
initiate dialysis (despite the presence of encephalopathy).

Activity
Instruct patients with significant symptoms to continue bed rest.

Further Inpatient Care

Admit patients for dialysis and further workup.

Further Outpatient Care

Schedule maintenance hemodialysis for patients who have ESRD.

Carefully monitor mental status.

Inpatient & Outpatient Medications

Administer medications (eg, iron, erythropoietin, phosphate binders, vitamin D analogues) for
patients with ESRD to optimize their quality of life.
Avoid sedatives.

Transfer

Patients may require transfer to a facility that can provide emergent hemodialysis.

Deterrence/Prevention

Refer patients with chronic kidney disease to a nephrologist for regular monitoring of CrCl so
that dialysis may be initiated before encephalopathy develops.

Complications

Seizures
Coma
Death

Prognosis

With prompt dialytic therapy, the mortality rate is low.