Effects of Hemodiafiltration and High Flux Hemodialysis on Nerve Excitability in End-Stage Kidney Disease

Objectives Peripheral neuropathy is the most common neurological complication in end-stage kidney disease. While high flux hemodialysis (HFHD) and hemodiafiltration (HDF) have become the preferred options for extracorporeal dialysis therapy, the effects of these treatments on nerve excitability have not yet been examined. Methods An observational proof-of-concept study of nerve excitability and neuropathy was undertaken in an incident dialysis population (n = 17) receiving either HFHD or HDF. Nerve excitability techniques were utilised to assess nerve ion channel function and membrane potential, in conjunction with clinical assessment and standard nerve conduction studies. A mathematical model of axonal excitability was used to investigate the underlying basis of the observed changes. Nerve excitability was recorded from the median nerve, before, during and after a single dialysis session and correlated with corresponding biochemical markers. Differences in nerve excitability were compared to normal controls with longitudinal follow-up over an 18 month period. Results Nerve excitability was performed in patient cohorts treated with either HFHD (n = 9) or online HDF (n = 8), with similar neuropathy status. Nerve excitability measures in HDF-treated patients were significantly closer to normal values compared to HFHD patients obtained over the course of a dialysis session (p<0.05). Longitudinal studies revealed stability of nerve excitability findings, and thus maintenance of improved nerve function in the HDF group. Conclusions This study has provided evidence that nerve excitability in HDF-treated patients is significantly closer to normal values prior to dialysis, across a single dialysis session and at longitudinal follow-up. These findings offer promise for the management of neuropathy in ESKD and should be confirmed in randomised trials.

[1]  David Burke,et al.  The voltage dependence of Ih in human myelinated axons , 2012, The Journal of physiology.

[2]  M. Kiernan,et al.  Modulatory effects on axonal function after intravenous immunoglobulin therapy in chronic inflammatory demyelinating polyneuropathy. , 2011, Archives of neurology.

[3]  M. Kiernan,et al.  Neurological complications of chronic kidney disease , 2009, Nature Reviews Neurology.

[4]  E. Stålberg,et al.  Clinical and electrophysiologic findings in dialysis patients. , 2009, Journal of electromyography and kinesiology : official journal of the International Society of Electrophysiological Kinesiology.

[5]  M. Friedlander,et al.  Acute abnormalities of sensory nerve function associated with oxaliplatin-induced neurotoxicity. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[6]  C. Ronco,et al.  The best dialysis therapy? Results from an international survey among nephrology professionals , 2008, NDT plus.

[7]  M. Kiernan,et al.  Nerve function and dysfunction in acute intermittent porphyria. , 2008, Brain : a journal of neurology.

[8]  D. Vlassopoulos,et al.  Inflammation and Oxidative Stress in Patients on Hemodiafiltration , 2008, American Journal of Nephrology.

[9]  M. Kiernan,et al.  Assessment of nerve excitability in toxic and metabolic neuropathies , 2008, Journal of the peripheral nervous system : JPNS.

[10]  D. Burke,et al.  Plasticity of inwardly rectifying conductances following a corticospinal lesion in human subjects , 2007, The Journal of physiology.

[11]  M. Kiernan,et al.  Uremic neuropathy: Clinical features and new pathophysiological insights , 2007, Muscle & nerve.

[12]  H. Schiffl Prospective randomized cross-over long-term comparison of online haemodiafiltration and ultrapure high-flux haemodialysis. , 2007, European journal of medical research.

[13]  C. Tetta,et al.  On-line hemodiafiltration reduces the proinflammatory CD14+CD16+ monocyte-derived dendritic cells: A prospective, crossover study. , 2006, Journal of the American Society of Nephrology : JASN.

[14]  B W Gillespie,et al.  Mortality risk for patients receiving hemodiafiltration versus hemodialysis: European results from the DOPPS. , 2006, Kidney international.

[15]  M. Kiernan,et al.  Ischaemia induces paradoxical changes in axonal excitability in end-stage kidney disease. , 2006, Brain : a journal of neurology.

[16]  M. Kiernan,et al.  Sensory nerve excitability and neuropathy in end stage kidney disease , 2006, Journal of Neurology, Neurosurgery & Psychiatry.

[17]  M. Kiernan,et al.  Altered motor nerve excitability in end-stage kidney disease. , 2005, Brain : a journal of neurology.

[18]  Peter K. Stys,et al.  General mechanisms of axonal damage and its prevention , 2005, Journal of the Neurological Sciences.

[19]  D. Burke,et al.  Acute tetrodotoxin‐induced neurotoxicity after ingestion of puffer fish , 2005, Annals of neurology.

[20]  N. Murray,et al.  Has potassium been prematurely discarded as a contributing factor to the development of uraemic neuropathy? , 2004, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[21]  Francesco Locatelli,et al.  Effect of dialysis dose and membrane flux in maintenance hemodialysis. , 2003, The New England journal of medicine.

[22]  G. Kraatz,et al.  On-line Production of Ultrapure Substitution Fluid Reduces TNF-alpha- and IL-6 Release in Patients on Hemodiafiltration Therapy , 2003, The International journal of artificial organs.

[23]  N. Murray,et al.  Nerve excitability changes in chronic renal failure indicate membrane depolarization due to hyperkalaemia. , 2002, Brain : a journal of neurology.

[24]  B. Falck,et al.  Neurophysiologic parameters and symptoms in chronic renal failure , 2002, Muscle & nerve.

[25]  Chiu-Ching Huang,et al.  Long-Term On-Line Hemodiafiltration Reduces Predialysis Beta-2-Microglobulin Levels in Chronic Hemodialysis Patients , 2001, Blood Purification.

[26]  H. Bostock,et al.  Effects of membrane polarization and ischaemia on the excitability properties of human motor axons. , 2000, Brain : a journal of neurology.

[27]  W Samtleben,et al.  A comparison of on-line hemodiafiltration and high-flux hemodialysis: a prospective clinical study. , 2000, Journal of the American Society of Nephrology : JASN.

[28]  D. Burke,et al.  Multiple measures of axonal excitability: A new approach in clinical testing , 2000, Muscle & nerve.

[29]  D. Cornblath,et al.  Total neuropathy score , 1999, Neurology.

[30]  R. Vanholder,et al.  Peripheral motor and sensory nerve conduction studies in haemodialysis patients. A study of 54 patients. , 1998, Electromyography and clinical neurophysiology.

[31]  J T Daugirdas,et al.  Comparison of methods to predict equilibrated Kt/V in the HEMO Pilot Study. , 1997, Kidney international.

[32]  E. Lehning,et al.  Mechanisms of Injury‐Induced Calcium Entry into Peripheral Nerve Myelinated Axons: Role of Reverse Sodium‐Calcium Exchange , 1996, Journal of neurochemistry.

[33]  Werner Vogel,et al.  Voltage-clamp studies in axons: Macroscopic and single-channel currents , 1995 .

[34]  D. Burke Microneurography, impulse conduction, and paresthesias , 1993, Muscle & nerve.

[35]  H Bostock,et al.  Changes in excitability of human motor axons underlying post‐ischaemic fasciculations: evidence for two stable states. , 1991, The Journal of physiology.

[36]  E. Barrett,et al.  Intracellular recording from vertebrate myelinated axons: mechanism of the depolarizing afterpotential , 1982, The Journal of physiology.

[37]  B. Scribner,et al.  The middle molecule hypothesis in perspective. , 1981, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[38]  K. Hruska,et al.  Parathyroid hormone metabolism and its potential as a uremic toxin. , 1980, The American journal of physiology.

[39]  S. Massry,et al.  Effect of parathyroid hormone and uremia on peripheral nerve calcium and motor nerve conduction velocity. , 1978, The Journal of clinical investigation.

[40]  William Clark,et al.  Serum beta-2 microglobulin levels predict mortality in dialysis patients: results of the HEMO study. , 2006, Journal of the American Society of Nephrology : JASN.

[41]  R. Hojs,et al.  Polyneuropathy in hemodialysis patients: The most sensitive electrophysiological parameters and dialysis adequacy , 2006, Wiener klinische Wochenschrift.

[42]  S. Mandolfo,et al.  Effect of hemodialysis and hemodiafiltration on uremic neuropathy. , 1991, Blood purification.