OBJECTIVE: 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). METHODS: 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 60s. Serum concentrations of putative neurotoxins including potassium, urea, parathyroid hormone and beta-2-microglobulin were also measured. RESULTS: 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. CONCLUSIONS: Our findings suggest that Na(+)/K(+) pump function is not impaired in patients with ESKD. SIGNIFICANCE: 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.
OBJECTIVE: 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). METHODS: 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 60s. Serum concentrations of putative neurotoxins including potassium, urea, parathyroid hormone and beta-2-microglobulin were also measured. RESULTS: 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. CONCLUSIONS: Our findings suggest that Na(+)/K(+) pump function is not impaired in patients with ESKD. SIGNIFICANCE: 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.
Authors: Jeremy Chung Bo Chiang; Ria Arnold; Roshan Dhanapalaratnam; Maria Markoulli; Arun V Krishnan Journal: Pharmaceuticals (Basel) Date: 2022-05-15
Authors: Ranjani N Moorthi; Simit Doshi; Linda F Fried; Sharon M Moe; Mark J Sarnak; Suzanne Satterfield; Ann V Schwartz; Michael Shlipak; Brittney S Lange-Maia; Tamara B Harris; Anne B Newman; Elsa S Strotmeyer Journal: Nephrol Dial Transplant Date: 2019-04-01 Impact factor: 5.992
Authors: Alexandru D P Papoiu; Nichole M Emerson; Tejesh S Patel; Robert A Kraft; Rodrigo Valdes-Rodriguez; Leigh A Nattkemper; Robert C Coghill; Gil Yosipovitch Journal: J Neurophysiol Date: 2014-06-18 Impact factor: 2.714