Table 2.

Summary of neurological complications and potential contributors.

	Condition	Presentation	Contributing factors	Distinguishing tests	Treatments
Altered mental status
Chronic	Stroke Brain, spinal cord, or retinal cell death attributable to ischemia, based on neuropathological, neuroimaging, and/or clinical evidence of permanent injury. Silent infarction – causes no known symptoms	Neurological deficit will depend on the brain region affected and the type of stroke but features may include: headache, nausea, vertigo, altered mental status, altered vision, aphasia, weakness, facial droop, paralysis. Asymptomatic Mild cognitive impairment	Common between stroke, cognitive impairment and dementia Direct effects of Uraemia Vascular damage, endothelial dysfunction, inflammation, oxidative stress, anaemia, hyperhomocysteinaemia, hypercoagulable states, parathyroid hormone, guanidine compounds, cystatin-C Secondary causes Hypertension, dyslipidaemia, atrial fibrillation, diabetes, increased age, smoking status, secondary hyperparathyroidism Iatrogenic causes EPO-stimulating agents Dialysis via perfusion-related insults	Imaging: CT or MRI Common features include: silent cerebral infarcts, cerebral microbleeds, white matter abnormalities or atrophy	Acute; see Dad and Weiner12 Long-term reduce risk factors: Hypertension Lipid profile Anaemia* Atrial fibrillation
	Cognitive impairment A new deficit in two or more areas of cognitive function	Altered memory, executive function, attention, concentration, perception and/or language skills		MMSE	As above Renal Tx
	Dementia Persistent cognitive decline and behavioural disturbance	As above with a severity that interferes with independence and daily functioning		Formal Neuro-psychological assessment	Patient/ family education and support plans
	Dialysis dementia Progressive dementia related to chronic Aluminium exposure	Dysarthria, dysphasia, dysgraphia, apathy and depression progressing to convulsions, psychosis and frank dementia	Iatrogenic cause: Chronic exposure to aluminium in dialysis water over years. Now rare due to routine removal of aluminium from dialysis water using reverse osmosis.	Progressive when untreated.
Acute	Encephalopathy Altered brain function induced by an agent or condition Posterior Reversible Encephalopathy Syndrome (PRES)	Altered metal status sometimes accompanied by generalised or focal motor disturbances. Altered mental status: sensorial clouding, delirium, fatigue, apathy, impaired concentration. Motor disturbances: tremor, fasciculations, asterixis. Late signs: hallucinations, seizures, coma.	Direct effects of Uraemia Uraemic metabolites, guanidino compounds, parathyroid hormone, fluid and electrolyte disturbances Secondary Causes Hypertension Thiamine deficiency Iatrogenic Causes EPO induced hypertension, Polypharmacy, Transplant rejection and Acute aluminium induced encephalopathy (may occur in dialysis patients given desferrioxamine as a chelating agent)	Blood tests including complete blood count, electrolyte panel, glucose, urea, vitamin B12, folic acid, thyroid function, liver enzymes and ammonia. EEG Imaging	Rectify underlying cause. Dialysis to normalise uraemia. Normalise overt hypertension. Vitamins for thiamine deficiency.
	Dialysis disequilibrium syndrome Cerebral oedema during or after dialysis	Mild: Headache, nausea, disorientation, dizziness, restlessness, blurred vision and/or asterixis Severe: Seizures, central pontine demyelination, coma	Iatrogenic cause: Rapid changes in urea and other osmolites induced by dialysis and causing cerebral oedema. Most common in ESKD patients following initiation of dialysis treatment or following a sudden change of dialysis regime.	DOE During or immediately after dialysis. Papilloedema CT or MRI	Preventative: gradual reduction in BUN reduced duration and blood flow rate.
Physical disability
Chronic	Peripheral neuropathy Disease or death of the peripheral nerves	Altered sensation such as: numbness, paraesthesia and pain progressing to weakness and wasting maximal distally with greater involvement of lower limbs than upper.	Direct effects of uraemia Uraemic metabolites, Potassium Secondary causes Diabetes, peripheral vascular disease Iatrogenic causes Immunosuppressive medications (CNI)	Nerve conduction studies Stocking and glove distribution. Chronic disease course	Potassium restriction Pharmacological pain management
	Autonomic neuropathy Disease or death of autonomic nerves	Orthostatic intolerance, syncope, brady-or-tachyarrhythmia, palpitations, nausea, pallor, reduced capacity for exercise, impotence, bladder and/or bowel dysfunction, thermoregulatory and secretomotor abnormalities.	Direct effects of uraemia Cardiovascular autonomic dysfunction is thought to be independent of uraemia-related toxins Secondary causes Hypertension, diabetes	Cardiac and pupillary reflexes, sudomotor function and blood pressure control. Heart rate variability	Renal Tx Midodrine for intradialytic hypotension Sildenafil for impotence
	Myopathy Disease of muscle tissue	Proximal muscle weakness in the muscles of the lower limb Reduced endurance and capacity for exercise	Direct effects of uraemia Uraemic metabolite, hyperparathyroidism, impaired potassium regulation, carnitine deficiency, oxidative stress, metabolic bone disease with vitamin D deficiency Secondary causes Diabetes	DOE on clinical neurological examination	Adequate dialysis Exercise program Nutrition

CT: computed tomography; MRI: magnetic resonance imaging; EPO: erythropoiesis; MMSE: Mini-Mental State Examination; Tx: transplant; PRES: posterior reversible encephalopathy syndrome; DOE: diagnosis of exclusion; EEG: electroencephalogram; ESKD: end-stage kidney disease; CNI: calcineurin inhibitor. Anaemia*: correction of anaemia within the KDOQI guidelines of haemoglobin levels between 11 and 12 g/dl.