Uremic Encephalopathy 1.Background Uremic encephalopathy is an organic brain disorder.

It develops in patients with acute or chronic renal failure, usually when creatinine clearance ( r l! levels fall and remain below 1" m#$min.%1, &, ', () *anifestations of this syndrome vary from mild symptoms (eg, lassitude, fatigue! to severe symptoms (eg, sei+ures, coma!. ,everity and progression depend on the rate of decline in renal function- thus, symptoms are usually worse in patients with acute renal failure. .rompt identification of uremia as the cause of encephalopathy is essential because symptoms are readily reversible following initiation of dialysis.%", /) &. .athophysiology

Uremic encephalopathy has a comple0 pathophysiology, and many to0ins that accumulate in kidney failure may be contributive. .arathyroid hormone (.12! likely contributes to uremic encephalopathy.%3) ,econdary hyperparathyroidism, which occurs in kidney failure, causes an increase in calcium content in the cerebral corte0. In animal models with uremia, EE4 changes were typical of those observed in patients with renal failure. In uremic patients with secondary hyperparathyroidism, EE4 changes have been shown to improve after medical suppression of .12 or parathyroidectomy. 1he specific mechanism by which .12 causes disturbance in brain function is unclear, but it may be caused by increases in intracellular concentration of calcium in brain cells. 2owever, since the encephalopathy improves with dialysis, which does not have a marked effect on .12 levels, hyperparathyroidism is not thought to be the main cause. 5nother theory about the etiology of uremic encephalopathy suggests imbalances of neurotransmitter amino acids within the brain. 6uring the early phase of uremic encephalopathy, plasma and cerebrospinal fluid ( ,7! determinations indicate that levels of glycine increase and levels of glutamine and 45B5 decrease- additionally, alterations occur in metabolism of dopamine and serotonin in the brain, which may lead to early symptoms (eg, sensorial clouding!. 5s uremia progresses, it has been proposed that the accumulation of guanidino compounds results in activation of e0citatory 89methyl969aspartate (8*65! receptors and inhibition of inhibitory 45B5 receptors, which may cause myoclonus and sei+ures.%", :, ;) 5 study of acute kidney in<ury in mice found evidence of a blood9brain barrier disruption from such in<ury, with increased neuronal pyknosis and microgliosis. In addition, proinflammatory chemokines were increased in brain tissue.%1=)

8umerous other uremic to0ins may contribute to uremic encephalopathy, but there has been a notable lack of research in this area. 5lthough the encephalopathy correlates roughly with BU8 level, urea is not itself thought to be causative. '. Epidemiology 7re>uency United ,tates *ost patients with a r l level less than 1=? of normal probably develop some degree of encephalopathy- however, they may not be clearly symptomatic. In one pediatric study, encephalopathy occurred in (=? of the children with a BU8 level greater than ;= mg$d#. 5s the BU8 level increased, the likelihood of these children developing convulsions increased.%11) *ortality$*orbidity ,ymptoms include somnolence and decreased mentation. 5steri0is is usually present. 1hese findings are reversible following initiation of dialysis and recovery of renal function in patients with acute renal failure. ,ymptoms are also reversible following the institution of dialysis or renal transplantation in patients with chronic renal insufficiency. 1he severe complications (ie, sei+ures, coma! can lead to death. Early recognition of encephalopathy in the setting of decreased renal function is crucial to prevent morbidity or mortality. @ace 8o racial predilection e0ists. ,e0 8o significant association between se0 and incidence e0ists. 5ge Uremic encephalopathy may develop at any age.

Uremic Encephalopathy .resentation

(.2istory Early symptoms 5nore0ia 8ausea @estlessness 6rowsiness 6iminished ability to concentrate ,lowed cognitive functions

*ore severe symptoms Aomiting Emotional volatility 6ecreased cognitive function 6isorientation onfusion Bi+arre behavior 5s uremic encephalopathy progresses, patients may develop myoclonus, asteri0is, sei+ures, stupor, and coma.

". .hysical 5ltered mental status (confusion! ranial nerve signs (nystagmus! .apilledema 2yperrefle0ia, clonus, asteri0is ,tupor oma occurs only if uremia remains untreated and progresses. /. causes Uremic encephalopathy may occur in a patient affected with acute kidney in<ury or chronic kidney failure of any etiology.

3. @E7E@E8 E Uremic Encephalopathy Borkup #aboratory ,tudies Electrolytes, BU8, creatinine, and glucose%1&) *arkedly elevated BU8 and creatinine levels are seen in uremic encephalopathy. Cbtain serum electrolyte and glucose measurements to rule out hyponatremia, hypernatremia, hyperglycemia, and hyperosmolar syndromes as the cause of encephalopathy. Cbtain a complete blood cell count to detect leukocytosis, which may suggest an infectious cause and determine whether anemia is present. (5nemia may contribute to the severity of mental alterations.! Cbtain serum calcium, phosphate, and .12 levels to determine the presence of hypercalcemia, hypophosphatemia, and severe hyperparathyroidism, which cause metabolic encephalopathy. ,erum magnesium levels may be elevated in a patient with renal insufficiency, particularly if the patient is ingesting magnesium9containing antacids. 2ypermagnesemia may manifest as encephalopathy. Crder a to0icology screen in all patients. *edication levels 6etermine drug levels because medications may accumulate in patients with kidney failure and

contribute to encephalopathy (eg, digo0in, lithium!. ,ome medications cannot be detected and are e0creted by the kidney. 1hese may also accumulate in patients with kidney failure, resulting in encephalopathy (eg, penicillin, cimetidine, meperidine, baclofen!. Imaging ,tudies ,evere symptoms Cbtain an *@I or head 1 scan for a uremic patient who presents with severe neurologic symptoms to rule out structural abnormalities (eg, cerebrovascular accident, intracranial mass!. 5 1 scan does not demonstrate any characteristic findings for uremic encephalopathy. Bith milder symptoms, initially treat the patient with dialysis and observe for neurologic improvement. :. Cther 1ests Electroencephalogram 5n EE4 is commonly performed on patients with metabolic encephalopathy. 7indings typically include the followingD (1! slowing and loss of alpha fre>uency waves, (&! disorgani+ation, and ('! intermittent bursts of theta and delta waves with slow background activity. @eduction in fre>uency of EE4 waves correlates with the decrease in renal function and the alterations in cerebral function. 5fter the initial period of dialysis, clinical stabili+ation may occur while the EE4 findings do not improve. Eventually, EE4 results move toward normal. 5side from the routine EE4, evoked potentials (E.s! (ie, EE4 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. hronic renal failure prolongs latency of the cortical visual9evoked response. 5uditory9evoked responses are generally not altered in uremia, but delays in the cortical potential of the somatosensory9evoked response do occur. ognitive function testsD ,everal cognitive function tests are used to evaluate uremic encephalopathy. Uremia may result in worse performance on the trail9making test, which measures psychomotor speed- the continuous memory test, which measures short9term recognition- and the choice reaction time test, which measures simple decision making. 5lterations in choice reaction time appear to correlate best with renal failure. .rocedures #umbar puncture #umbar puncture is not routinely performed- however, it may be indicated to find other causes of encephalopathy if a patientEs mental status does not improve after initiation of dialysis. 8o specific ,7 finding indicates uremic encephalopathy.

;. 1reatment

a. *edical are 8o medications are specific to the treatment of encephalopathy. 9 1he 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!. 5fter beginning dialysis, the patient generally improves clinically, although EE4 findings may not improve immediately. 9In patients with end9stage renal disease (E,@6!, EE4 abnormalities generally improve after several months but may not completely normali+e. 95ddress the following factors when treating uremic encephalopathy, which are also included in the standard care of any patient with E,@6D F5de>uacy of dialysis F orrection of anemia F@egulation of calcium and phosphate metabolism b. onsultations onsult a neurologist if symptoms do not improve upon initiation of dialysis therapy. onsult a vascular surgeon for placement of vascular access in patients with E,@6. @efer patients with E,@6 to a dietitian familiar with renal diseases. c. 6iet 9 1o avoid malnutrition in patients with E,@6, maintain ade>uate protein intake (G1 g$kg$d! and initiate dialysis (despite the presence of encephalopathy!.

d. 5ctivity 9 Instruct patients with significant symptoms to continue bed rest.

7urther Inpatient are 5dmit patients for dialysis and further workup. 7urther Cutpatient are ,chedule maintenance hemodialysis for patients who have E,@6. arefully monitor mental status. Inpatient H Cutpatient *edications 5dminister medications (eg, iron, erythropoietin, phosphate binders, vitamin 6 analogues! for

patients with E,@6 to optimi+e their >uality of life. 5void sedatives. 1ransfer .atients may re>uire transfer to a facility that can provide emergent hemodialysis. 6eterrence$.revention @efer patients with chronic kidney disease to a nephrologist for regular monitoring of r l so that dialysis may be initiated before encephalopathy develops. omplications ,ei+ures oma 6eath .rognosis Bith prompt dialytic therapy,