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

Abstract

ObjectivesPeripheral 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.MethodsAn 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.ResultsNerve 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.ConclusionsThis 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.

Randomized, Controlled Trial of the Effect of Dietary Potassium Restriction on Nerve Function in CKD

“…The primary outcome measure was the change from baseline to final study visit in the total neuropathy score, an outcome measure that has been used in previous studies of neuropathy in diabetes (14) and CKD (9,15,16). This scoring system assesses changes in eight different clinical domains, including symptoms, examination findings, and lower limb nerve conduction values, and assigns a score from zero to four for each domain.…”

“…Neurophysiologic studies were conducted using specialized nerve excitability techniques. Nerve excitability assessment is a clinical method that provides information on ion channel function in peripheral nerves (17), which has been used in previous studies of nerve function in CKD (9,10,16). Excitability studies were performed using previously described threshold tracking protocols applied to the median nerve at the wrist (18).…”

“…Excitability studies were performed using previously described threshold tracking protocols applied to the median nerve at the wrist (18). Excitability analyses were restricted to two composite scores composed of parameters that are sensitive to changes in membrane potential and have been shown to be abnormal in previous studies of CKD (8,10,16). Specifically, composite score 1 was superexcitability plus depolarizing threshold electrotonus 10-20 ms, and composite score 2 was superexcitability plus hyperpolarizing threshold electrotonus 90-100 ms (17).…”

“…Before commencement of the trial, the neuropathy symptom score was abandoned, and the total neuropathy score (14) was used in its place. The total neuropathy score has been used extensively in studies of neuropathy related to diabetes (14) and CKD (9,15,16). It has the added advantage of measuring neuropathy severity on a continuous scale and incorporates neuropathic symptoms, clinical signs, and nerve conduction values.…”

Clinical Expectation of Online Hemodiafiltration: A Japanese Perspective

“…Many clinical effects for online HDF have been reported. These include the reduction of dialysis-related hypotension [6], improvement of anemia with sparing erythropoiesis-stimulating agent dosage [7,8,9], prevention of the deterioration of dialysis-related amyloidosis, improvement of the nutritional status by reducing inflammatory stress [10], cardiovascular protection by preserving vascular endothelial cell function [11,12], relief of both peripheral neuropathy and insomnia [13,14], preservation of residual renal function [15] and ultimately a survival benefit [3]. These effects are due to the better quality of dialysis fluid, the greater efficiency of removing uremic accumulates and the better hemodynamic stability during treatment resulting in prevention of dialysis-related hypotension.…”