Neuropathy, axonal Na +/K + pump function and activity-dependent excitability changes in end-stage kidney disease

• Published in: Clinical neurophysiology 2006-05, Vol.117 (5), p.992-999
• 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: Adolescent; Adult; Aged; Axons - pathology; Axons - physiology; Biological and medical sciences; Case-Control Studies; Electric Stimulation - methods; Electrodiagnosis. Electric activity recording; Female; Humans; Investigative techniques, diagnostic techniques (general aspects); Kidney Failure, Chronic - metabolism; Kidney Failure, Chronic - pathology; Kidney Failure, Chronic - physiopathology; Kidney Failure, Chronic - therapy; Male; Medical sciences; Membrane potential; Middle Aged; Motor Activity; Muscle Contraction - physiology; Na +/K + pump; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Nerve excitability; Nervous system; Neural Conduction - physiology; Parathyroid Hormone - blood; Peripheral Nervous System Diseases - metabolism; Peripheral Nervous System Diseases - pathology; Peripheral Nervous System Diseases - physiopathology; Potassium; Potassium - blood; Renal Dialysis - methods; Renal failure; Serum Globulins - metabolism; Sodium-Potassium-Exchanging ATPase - physiology; Uraemic neuropathy; Urea - metabolism
• ISSN: 1388-2457; 1872-8952
• DOI: 10.1016/j.clinph.2006.02.002

To investigate the mechanisms underlying peripheral neuropathy and to provide insights into axonal Na +/K + pump function in patients with end-stage kidney disease (ESKD). Nerve excitability was assessed in 10 ESKD patients before and after a single session of haemodialysis and in 29 age-matched control subjects. Changes in excitability were recorded at baseline and following maximal voluntary contraction (MVC) of abductor pollicis brevis (APB) for 60 s. Serum concentrations of putative neurotoxins including potassium, urea, parathyroid hormone and beta-2-microglobulin were also measured. Baseline excitability values were consistent with axonal depolarisation prior to dialysis. Following maximal voluntary contraction (MVC), there was an increase in threshold, which was associated with reduced strength-duration time constant and increased superexcitability, consistent with axonal hyperpolarisation. These changes were quantitatively similar for patients and controls, arguing against any significant reduction in the axonal Na +/K + pump in ESKD. Following dialysis, activity-dependent changes were less in ESKD, which suggests greater Na +/K + pump activity prior to dialysis, the opposite of the changes expected with reduced Na +/K + pump function. The reduced post-contraction threshold change in post-dialysis recordings is likely to be secondary to relative hyperpolarisation of the axonal membrane following dialysis and reduction in K + concentration. Our findings suggest that Na +/K + pump function is not impaired in patients with ESKD. Pre-dialysis excitability changes in ESKD patients may be explained on the basis of hyperkalaemia. Alteration in Na +/K + pump function does not appear to be a contributing factor to the development of neuropathy in ESKD patients.