Uremic Encephalopathy

Uraemic encephalopathy is a reversible metabolic brain dysfunction in patients with advanced acute or chronic kidney failure, resulting from accumulation of uraemic toxins.

• Typical eGFR below 10–15 mL/min, but may occur at higher levels in rapidly progressive AKI.
• Mechanisms: retained guanidino compounds, middle molecules, indoxyl sulphate, parathyroid hormone-mediated calcium entry into neurons, neurotransmitter imbalance (GABA, glutamate), oxidative stress, blood-brain barrier disruption, osmotic shifts.
• Often accompanied by other metabolic disturbances: hyponatraemia, hypocalcaemia, acidosis, hyperammonaemia, hypertension, anaemia, thiamine deficiency.
• Complications: seizures, coma, subdural haematoma (uraemic platelet dysfunction), dialysis disequilibrium syndrome upon initiation of dialysis, Wernicke encephalopathy.

• Early: fatigue, poor concentration, apathy, insomnia, irritability, memory impairment.
• Progressive: confusion, delirium, hallucinations, agitation, asterixis, myoclonus, tremor, dysarthria, hyperreflexia, restless legs, cramps.
• Late: seizures (generalised or focal), stupor, coma; Kussmaul respiration from acidosis.
• Associated: pericarditis, pruritus, nausea, anorexia, bleeding, peripheral neuropathy.
• Multifocal myoclonus and asterixis are typical; focal deficits are unusual.

• Clinical diagnosis in the context of severe renal impairment.
• Urea (BUN over 100 mg/dL typical but poorly correlates), creatinine, eGFR, electrolytes, calcium, phosphate, bicarbonate, glucose, ammonia, liver tests, magnesium, blood gas.
• Exclude other causes: hypoglycaemia, hypertensive encephalopathy/PRES, stroke, intracranial haemorrhage (CT head), infection (meningitis), drug toxicity (gabapentin, pregabalin, opioids, lithium, cefepime, metformin), hepatic encephalopathy, Wernicke encephalopathy, thrombotic microangiopathy, dialysis-related aluminium toxicity.
• EEG: diffuse slowing, triphasic waves; MRI brain: basal ganglia or PRES-like changes, subdural effusion.
• Drug levels and review of renally cleared drugs.

• Renal replacement therapy is the definitive treatment: initiate dialysis urgently (haemodialysis or continuous therapy); improvement within days, though complete recovery may take weeks.
• To limit dialysis disequilibrium in severely uraemic patients: short initial sessions (2 hours), low blood flow (150–200 mL/min), urea reduction under 30–40%, high dialysate sodium (145 mmol/L), mannitol 0.5 g/kg or hypertonic saline in prophylaxis.
• Treat reversible contributors: correct electrolytes, acidosis (sodium bicarbonate), hypertension, anaemia, hypoglycaemia; thiamine 100–500 mg IV for suspected deficiency.
• Seizures: benzodiazepines (lorazepam 2–4 mg IV), levetiracetam (renally dosed: 500 mg loading, then 250–500 mg twice daily; give supplemental dose after dialysis), avoid phenytoin without free level monitoring; avoid drugs that lower seizure threshold (cefepime, imipenem, tramadol, bupropion, theophylline, high-dose penicillins).
• Review and renally adjust all medications; stop gabapentinoids and morphine, use fentanyl or hydromorphone for analgesia.
• Haloperidol 0.5–1 mg for severe agitation (with caution) and non-pharmacological delirium management.
• Prolonged dialysis dependence: optimise dialysis adequacy, treat anaemia (ESA), bone mineral disease; kidney transplantation in suitable patients.
• Prognosis: reversible with dialysis if treated promptly; cognitive impairment may persist in chronic uraemia.