Altered motor nerve excitability in end-stage kidney disease

• Published in: Brain (London, England : 1878) England : 1878), 2005-09, Vol.128 (9), p.2164-2174
• Main Authors: Krishnan, Arun V., Phoon, Richard K. S., Pussell, Bruce A., Charlesworth, John A., Bostock, Hugh, Kiernan, Matthew C.
• Format: Article
• Language: English
• Subjects: Action Potentials; Adolescent; Adult; Aged; Biological and medical sciences; CMAP = compound muscle action potential; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; EDB = extensor digitorum brevis; Electric Stimulation - methods; ESKD = end-stage kidney disease; Female; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Humans; Kidney Failure, Chronic - complications; Kidney Failure, Chronic - physiopathology; Kidney Failure, Chronic - therapy; Leg - innervation; Male; Medical sciences; membrane potential; Middle Aged; Motor Neurons - physiology; NCS = nerve conduction study; nerve excitability; Nervous system (semeiology, syndromes); Neural Conduction; Neurology; Neurotoxins - blood; NSS = neuropathy symptom score; Peripheral Nervous System Diseases - blood; Peripheral Nervous System Diseases - etiology; Peripheral Nervous System Diseases - physiopathology; potassium; Potassium - blood; PTH = parathyroid hormone; Renal Dialysis; SNAP = sensory nerve action potential; T-NSS = total neuropathy symptom score; TA = tibialis anterior; TEd = depolarizing threshold electrotonus; TEh = hyperpolarizing threshold electrotonus; threshold electrotonus; uraemic neuropathy; β-2M = β-2-microglobulin
• ISSN: 0006-8950; 1460-2156
• DOI: 10.1093/brain/awh558

Although multiple toxins have been implicated in the development of uraemic neuropathy, no causative agent has been identified. In the present study, the excitability properties of lower limb motor nerves in patients with end-stage kidney disease treated with haemodialysis were measured before, during and after a standard 5 h haemodialysis session, in an attempt to explore the pathophysiology of uraemic neuropathy. Compound muscle action potentials were recorded from tibialis anterior and extensor digitorum brevis, following stimulation of the common peroneal nerve in 14 patients. Measures of excitability were assessed in relation to changes in serum levels of potential neurotoxins, including potassium, calcium, urea, uric acid, parathyroid hormone and β-2-microglobulin. Before dialysis, measures of nerve excitability were significantly abnormal in the patient group for axons innervating tibialis anterior and extensor digitorum brevis, consistent with axonal depolarization: refractoriness was increased and superexcitability and depolarizing threshold electrotonus were reduced. Pre-dialysis excitability abnormalities were strongly correlated with serum K+. Correlation was also noted between the severity of symptoms and excitability abnormalities. Haemodialysis normalized the majority of nerve excitability parameters. In conclusion, lower limb motor axons in uraemic patients are depolarized before dialysis. The correlation between serum K+ and excitability measures indicates that hyperkalaemia is primarily responsible for uraemic depolarization, and a likely contributing factor to the development of neuropathy.