Barriers and enablers to exercise in kidney transplant recipients: Systematic review of qualitative studies.

BACKGROUND: Exercise has the potential to reduce the susceptibility to comorbidity and cardiovascular disease in kidney transplant recipients. However, kidney transplant recipients report lower levels of exercise compared to the general population, prompting an investigation into the barriers and enablers to exercise in this transplant cohort. OBJECTIVES: This systematic review aimed to explore and map the barriers and enablers to exercise in kidney transplant recipients. METHODS: Seven electronic databases were systematically searched. Themes were synthesised and then deductively categorised using the Theoretical Domains Framework. RESULTS: Eleven studies were included in the review. Commonly reported barriers to exercise were lack of exercise guidance (n = 9 studies), physical limitations (n = 5 studies) and a fear of harming the kidney (n = 7 studies). Enablers were a desire to return to normality (n = 5 studies), physical and mental benefits (n = 3 studies), goal setting and tracking improvements (n = 3 studies). At the local level, barriers identified by kidney transplant recipients were a lack of knowledge, fear of injuring the kidney, bad weather and physical limitations. Perceived enablers were already living an active lifestyle, mental benefits, exercise preferences and social support. CONCLUSION: Key findings of this research were an increased demand for specific/explicit exercise information regarding type and intensity, and personalised guidance and support for kidney transplant recipients after transplantation. These findings can be used to inform the development of exercise resources and interventions for kidney transplant recipients and their health care professionals within the local community and at a greater level.

Preferences of people with chronic kidney disease regarding digital health interventions that promote healthy lifestyle: qualitative systematic review with meta-ethnography.

OBJECTIVES: Diet and physical activity are crucial for people with chronic kidney disease (CKD) to maintain good health. Digital health interventions can increase access to lifestyle services. However, consumers' perspectives are unclear, which may reduce the capacity to develop interventions that align with specific needs and preferences. Therefore, this review aims to synthesise the preferences of people with CKD regarding digital health interventions that promote healthy lifestyle. DESIGN: Qualitative systematic review with meta-ethnography. DATA SOURCES: Databases Scopus, CENTRAL, MEDLINE, CINAHL and SPORTDiscus were searched between 2000 and 2023. ELIGIBILITY CRITERIA: Primary research papers that used qualitative exploration methods to explore the preferences of adults with CKD (≥18 years) regarding digital health interventions that promoted diet, physical activity or a combination of these health behaviours. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers screened title, abstract and full text. Discrepancies were resolved by a third reviewer. Consumers' quotes were extracted verbatim and synthesised into higher-order themes and subthemes. RESULTS: Database search yielded 5761 records. One record was identified following communication with a primary author. 15 papers were included. These papers comprised 197 consumers (mean age 51.0±7.2), including 83 people with CKD 1-5; 61 kidney transplant recipients; 53 people on dialysis. Sex was reported in 182 people, including 53% male. Five themes were generated regarding consumers' preferences for digital lifestyle interventions. These included simple instruction and engaging design; individualised interventions; virtual communities of care; education and action plans; and timely reminders and automated behavioural monitoring. CONCLUSION: Digital health interventions were considered an important mechanism to access lifestyle services. Consumers' preferences are important to ensure future interventions are tailored to specific needs and goals. Future research may consider applying the conceptual framework of consumers' preferences in this review to develop and evaluate the effect of a digital lifestyle intervention on health outcomes. PROSPERO REGISTRATION NUMBER: CRD42023411511.

Current and Emerging Pharmacotherapeutic Interventions for the Treatment of Peripheral Nerve Disorders.

Peripheral nerve disorders are caused by a range of different aetiologies. The range of causes include metabolic conditions such as diabetes, obesity and chronic kidney disease. Diabetic neuropathy may be associated with severe weakness and the loss of sensation, leading to gangrene and amputation in advanced cases. Recent studies have indicated a high prevalence of neuropathy in patients with chronic kidney disease, also known as uraemic neuropathy. Immune-mediated neuropathies including Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy may cause significant physical disability. As survival rates continue to improve in cancer, the prevalence of treatment complications, such as chemotherapy-induced peripheral neuropathy, has also increased in treated patients and survivors. Notably, peripheral neuropathy associated with these conditions may be chronic and long-lasting, drastically affecting the quality of life of affected individuals, and leading to a large socioeconomic burden. This review article explores some of the major emerging clinical and experimental therapeutic agents that have been investigated for the treatment of peripheral neuropathy due to metabolic, toxic and immune aetiologies.

Peripheral Neuropathy Phenotyping in Rat Models of Type 2 Diabetes Mellitus: Evaluating Uptake of the Neurodiab Guidelines and Identifying Future Directions.

Diabetic peripheral neuropathy (DPN) affects over half of type 2 diabetes mellitus (T2DM) patients, with an urgent need for effective pharmacotherapies. While many rat and mouse models of T2DM exist, the phenotyping of DPN has been challenging with inconsistencies across laboratories. To better characterize DPN in rodents, a consensus guideline was published in 2014 to accelerate the translation of preclinical findings. Here we review DPN phenotyping in rat models of T2DM against the 'Neurodiab' criteria to identify uptake of the guidelines and discuss how DPN phenotypes differ between models and according to diabetes duration and sex. A search of PubMed, Scopus and Web of Science databases identified 125 studies, categorised as either diet and/or chemically induced models or transgenic/spontaneous models of T2DM. The use of diet and chemically induced T2DM models has exceeded that of transgenic models in recent years, and the introduction of the Neurodiab guidelines has not appreciably increased the number of studies assessing all key DPN endpoints. Combined high-fat diet and low dose streptozotocin rat models are the most frequently used and well characterised. Overall, we recommend adherence to Neurodiab guidelines for creating better animal models of DPN to accelerate translation and drug development.

Peripheral nerve morphology and intraneural blood flow in chronic kidney disease with and without diabetes.

INTRODUCTION/AIMS: Sonographic alterations of peripheral nerves in pre-dialytic kidney disease are yet to be determined. We aimed to assess peripheral nerve cross-sectional area (CSA) and intraneural blood flow in patients with pre-dialytic chronic kidney disease (CKD) and diabetic kidney disease (DKD). METHODS: Subjects with CKD (n = 20) or DKD (n = 20) underwent ultrasound to assess CSA of the median and tibial nerves as well as intraneural blood flow of the median nerve. Blood flow was quantified using maximum perfusion intensity. Neuropathy was assessed using the Total Neuropathy Score. A 6-m timed walk test was also performed. Healthy controls (n = 28) were recruited for comparison. RESULTS: The DKD group had more severe neuropathy (p = .024), larger tibial nerve CSA (p = .002) and greater median nerve blood flow than the CKD group (p = .023). Blood flow correlated with serum potassium in disease groups (r = 0.652, p = .022). Disease groups had larger tibial nerve CSA than controls (p < .05). No blood flow was detected in controls. Tibial nerve enlargement was associated with slower maximal walking speeds in disease groups (r = -0.389, p = .021). DISCUSSION: Subjects with DKD demonstrated enlarged tibial nerve CSA and increased median nerve blood flow compared to those with CKD. Elevations in serum potassium were associated with increased blood flow. Sonographic alterations were detectable in pre-dialytic kidney disease compared to controls, highlighting the utility of ultrasound in the assessment of nerve pathology in these patient groups.

Adolescent exposure to a solid high-fat, high-sugar 'cafeteria' diet leads to more pronounced changes in metabolic measures and gut microbiome composition than liquid sugar in female rats.

Adolescence is a dynamic developmental period where unhealthy solid foods and sugar-sweetened beverages are routinely consumed. Regular consumption of solid 'junk' foods rich in fat and refined carbohydrate and sugar-sweetened beverages are independently associated with an increased risk of metabolic disease and altered gut microbiome composition. Here we used a validated rat model to determine the effects of a solid 'cafeteria' diet high in fat and sugar (Caf) and 10% liquid sucrose solution (Suc) on food intake, metabolic measures and gut microbiome composition. Sixty adolescent female Sprague-Dawley rats were fed standard chow with or without continuous access to Caf diet and/or Suc for 13 weeks (n = 15). Exposure to cafeteria diet and liquid sucrose each increased body weight gain and adiposity, with no synergistic effects. Gut microbiome alpha and beta diversity parameters were more strongly affected by exposure to Caf diet than access to liquid Suc. Nonetheless, providing liquid sucrose to rats fed chow altered gut microbiome beta diversity and significantly enriched the abundance of five taxa from order Clostridiales. By contrast, in the two groups fed Caf, Suc did not alter beta diversity, with few differentially abundant taxa between Caf and Caf + Suc groups. In sum, liquid sucrose and solid cafeteria diet exerted largely independent effects on metabolic and gut microbiome measures. Interventions targeting either solid junk foods or sugary beverages are likely to reduce diet-related disease burden.

Peripheral neuropathy: an important contributor to physical limitation and morbidity in stages 3 and 4 chronic kidney disease.

BACKGROUND: Impaired physical function drives adverse outcomes in chronic kidney disease (CKD). Peripheral neuropathy is highly prevalent in CKD, though its contribution to physical function in CKD patients is unknown. This study examined the relationships between peripheral neuropathy, walking speed and quality of life (QoL) in stages 3 and 4 CKD. METHODS: This was a prospective observational study investigating neuropathy in CKD patients with an estimated glomerular filtration rate (eGFR) 15-60 mL/min/1.73 m2. A total of 109 patients were consecutively recruited. The presence and severity of peripheral neuropathy was determined using the total neuropathy score. Walking speed was assessed at both usual and maximal speed, and QoL was assessed using the Short- Form 36 (SF-36) questionnaire. RESULTS: Peripheral neuropathy was highly prevalent: 40% demonstrated mild neuropathy and 37% had moderate-severe neuropathy. Increasing neuropathy severity was the primary predictor of reduced walking speed (R2 = -0.41, P < 0.001) and remained so after multivariable analysis adjustment for diabetes. This association was evident for both usual and maximal walking speeds. Neuropathy correlated significantly with low scores on multiple domains of SF-36 including physical function (r = -0.570, P < 0.001). Subanalysis according to diabetic status revealed a high prevalence of neuropathy both with and without diabetes; relationships to walking speed remained evident in subgroup analysis. However, those with diabetes demonstrated greater severity of neuropathy, slower walking speed and lower scores in QoL. CONCLUSIONS: Moderate to severe peripheral neuropathy was common in stages 3 and 4 CKD, associated with reduced walking speed independent of diabetes status and was correlated with patient-reported QoL. This suggests that neuropathy is an important contributor to declining physical function in CKD irrespective of diabetes status. Targeted diagnosis and management of peripheral neuropathy during CKD progression may improve functional outcomes and QoL.

Effect of exenatide on peripheral nerve excitability in type 2 diabetes.

OBJECTIVE: To assess the effect of exenatide (a GLP-1 receptor agonist), dipeptidyl peptidase-IV (DPP-IV) inhibitors, and sodium-glucose co-transporter 2 (SGLT-2) inhibitors on measures of peripheral nerve excitability in patients with type 2 diabetes. METHODS: Patients receiving either exenatide (n = 32), a DPP-IV inhibitor (n = 31), or a SGLT-2 inhibitor (n = 27) underwent motor nerve excitability assessments. Groups were similar in age, sex, HbA1c, diabetes duration, lipids, and neuropathy severity. An additional 10 subjects were assessed prospectively over 3 months while oral anti-hyperglycaemic therapy was kept constant. A cohort of healthy controls (n = 32) were recruited for comparison. RESULTS: Patients receiving a DPP-IV or SGLT-2 inhibitor demonstrated abnormalities in peak threshold reduction, S2 accommodation, superexcitability, and subexcitability. In contrast, patients treated with exenatide were observed to have normal nerve excitability. In the prospective arm, exenatide therapy was associated with an improvement in nerve function as patients demonstrated corrections in S2 accommodation, superexcitability, and subexcitability at follow-up. These changes were independent of the reductions in HbA1c following exenatide treatment. CONCLUSIONS: Exenatide was associated with an improvement in measures of nerve excitability in patients with type 2 diabetes. SIGNIFICANCE: Exenatide may improve peripheral nerve function in type 2 diabetes.

Effect of Hemodiafiltration on the Progression of Neuropathy with Kidney Failure: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Neuropathy is a common complication of kidney disease that lacks proven disease-modifying treatments. Hemodiafiltration improves clearance of uremic toxins and is associated with better nerve function than hemodialysis. We aimed to determine whether hemodiafiltration reduces the progression of neuropathy in people receiving hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Filtration in the Neuropathy of End-Stage Kidney Disease Symptom Evolution (FINESSE) study was an open-label, blinded end point assessment, controlled trial that randomized maintenance hemodialysis recipients to hemodiafiltration or high-flux hemodialysis for 48 months or until death or cessation of dialysis at four study centers. The primary outcome was the mean change in the yearly modified total neuropathy score from baseline, with time points weighted equally. RESULTS: A total of 124 participants were randomized and followed for a mean of 41 months. At baseline, neuropathy was present in 91 (73%) participants (modified total neuropathy score greater than or equal to two), and 38 (31%) had moderate to severe neuropathy (modified total neuropathy score 9-28). Convection volume in the hemodiafiltration arm was a median of 24.7 (interquartile range, 22.4-26.5) L. The mean modified total neuropathy score (SEM) worsened by 1.7 (0.4)/28 and 1.2 (0.4)/28 in the hemodiafiltration and hemodialysis groups, respectively, with a mean difference of 0.5 (95% confidence interval, -0.7 to 1.7; P=0.37). There was no difference in survival (hazard ratio, 1.24; 95% confidence interval, 0.61 to 2.51; log rank P=0.55) or any of the prespecified adverse events. There was no difference between groups in the number of participants who suffered an adverse event adjusted by follow-up time (relative risk, 1.05; 95% confidence interval, 0.83 to 1.32; P=0.68). CONCLUSIONS: Neuropathy is still a common complication of kidney disease without disease-altering therapy. Hemodiafiltration did not affect neuropathy progression compared with hemodialysis. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Filtration in the Neuropathy of End-Stage Kidney Disease Symptom Evolution (FINESSE), ACTRN12609000615280.

Impact of the metabolic syndrome on peripheral nerve structure and function in type 2 diabetes.

BACKGROUND AND PURPOSE: There is a strong association between the metabolic syndrome in diabetes and the development of peripheral neuropathy; however, the pathophysiological mechanisms remain unknown. METHODS: Participants with type 2 diabetes and metabolic syndrome (T2DM/MetS, n = 89) and type 2 diabetes alone (T2DM; n = 59) underwent median nerve ultrasound and excitability studies to assess peripheral nerve structure and function. A subset of T2DM/MetS (n = 24) and T2DM (n = 22) participants underwent confocal microscopy to assess central and inferior whorl corneal nerve structure. Neuropathy severity was assessed using the modified Toronto Clinical Neuropathy Score (mTCNS). Diabetes groups were similar for age, sex distribution, diabetes duration, hemoglobin A1c , insulin treatment, and renal function. Sixty healthy controls similar for age and sex distribution were recruited for comparison. RESULTS: Participants with T2DM/MetS manifested with a greater mTCNS compared to T2DM (p < 0.05). Median nerve cross-sectional area was larger in the T2DM/MetS group compared to the T2DM cohort (p < 0.05). Participants with T2DM/MetS had reductions in central (all p < 0.01) and inferior whorl (all p < 0.05) nerve measures. Compared to T2DM, the T2DM/MetS group demonstrated more severe changes in nerve excitability measures, which was due to reduced sodium channel permeability and sodium-potassium pump function. In comparison, only sodium channel permeability was reduced in the T2DM group. CONCLUSIONS: Compared to participants with type 2 diabetes alone, those with diabetes and metabolic syndrome manifested greater alterations in peripheral nerve structure and function, which may be due to reduced function of the sodium-potassium pump.

Evidence of Altered Peripheral Nerve Function in a Rodent Model of Diet-Induced Prediabetes.

Peripheral neuropathy (PN) is a debilitating complication of diabetes that affects >50% of patients. Recent evidence suggests that obesity and metabolic disease, which often precede diabetes diagnosis, may influence PN onset and severity. We examined this in a translationally relevant model of prediabetes induced by a cafeteria (CAF) diet in Sprague-Dawley rats (n = 15 CAF versus n = 15 control). Neuropathy phenotyping included nerve conduction, tactile sensitivity, intraepidermal nerve fiber density (IENFD) and nerve excitability testing, an in vivo measure of ion channel function and membrane potential. Metabolic phenotyping included body composition, blood glucose and lipids, plasma hormones and inflammatory cytokines. After 13 weeks diet, CAF-fed rats demonstrated prediabetes with significantly elevated fasting blood glucose, insulin and impaired glucose tolerance as well as obesity and dyslipidemia. Nerve conduction, tactile sensitivity and IENFD did not differ; however, superexcitability was significantly increased in CAF-fed rats. Mathematical modeling demonstrated this was consistent with a reduction in sodium-potassium pump current. Moreover, superexcitability correlated positively with insulin resistance and adiposity, and negatively with fasting high-density lipoprotein cholesterol. In conclusion, prediabetic rats over-consuming processed, palatable foods demonstrated altered nerve function that preceded overt PN. This work provides a relevant model for pathophysiological investigation of diabetic complications.

Altered peripheral nerve structure and function in latent autoimmune diabetes in adults.

AIM: The present study was undertaken to investigate mechanisms of peripheral nerve dysfunction in latent autoimmune diabetes in adults (LADA). MATERIALS AND METHODS: Participants with LADA (n = 15) underwent median nerve ultrasonography and nerve excitability to examine axonal structure and function, in comparison to cohorts of type 1 diabetes (n = 15), type 2 diabetes (n = 23) and healthy controls (n = 26). The LADA group was matched for diabetes duration, glycaemic control, and neuropathy severity with the type 1 and type 2 diabetes groups. A validated mathematical model of the human axon was utilized to investigate the pathophysiological basis of nerve dysfunction. RESULTS: The most severe changes in nerve structure and function were noted in the LADA group. The LADA cohort demonstrated a significant increase in nerve cross-sectional area compared to type 1 participants and controls. Compared to type 1 and 2 diabetes, measures of threshold electrotonus, which assesses nodal and internodal conductances, were significantly worse in LADA in response to both depolarising currents and hyperpolarising currents. In the recovery cycle, participants with LADA had a significant increase in the relative refractory period. Mathematical modelling of excitability recordings indicated the basis of nerve dysfunction in LADA was different to type 1 and 2 diabetes. CONCLUSIONS: Participants with LADA exhibited more severe changes in nerve function and different underlying pathophysiological mechanisms compared to participants with type 1 or 2 diabetes. Intensive management of risk factors to delay the progression of neuropathy in LADA may be required.

Relative contributions of diabetes and chronic kidney disease to neuropathy development in diabetic nephropathy patients.

OBJECTIVE: Chronic kidney disease (CKD) caused by diabetes is known as diabetic kidney disease (DKD). The present study aimed to examine the underlying mechanisms of axonal dysfunction and features of neuropathy in DKD compared to CKD and type 2 diabetes (T2DM) alone. METHODS: Patients with DKD (n = 30), CKD (n = 28) or T2DM (n = 40) and healthy controls (n = 41) underwent nerve excitability assessments to examine axonal function. Neuropathy was assessed using the Total Neuropathy Score. A validated mathematical model of human axons was utilised to provide an indication of the underlying causes of nerve pathophysiology. RESULTS: Total neuropathy score was significantly higher in patients with DKD compared to those with either CKD or T2DM (p < 0.05). In DKD, nerve excitability measures (S2 accommodation and superexcitability, p < 0.05) were more severely affected compared to both CKD and T2DM and worsened with increasing serum K+ (p < 0.01). Mathematical modelling indicated the basis for nerve dysfunction in DKD was an elevation of extracellular K+ and reductions in Na+ permeability and the hyperpolarisation-activated cation current, which was similar to CKD. CONCLUSIONS: Patients with DKD manifested a more severe neuropathy phenotype and shared features of nerve dysfunction to that of CKD. SIGNIFICANCE: The CKD, and not diabetes component, appears to underlie axonal pathophysiology in DKD.

Polymer brush based fluorescent immunosensor for direct monitoring of interleukin-1ß in rat blood.

A sandwich immunosensor was successfully developed for monitoring of interleukin-1ß (IL-1ß) in rat whole blood. The substrate stainless steel (SS) was first coated with a polydopamine layer and subsequently grafted with poly(ethylene glycol) methacrylate brushes, onto which a sandwich immunosensor was modified for detection of IL-1ß. The device has been successfully applied for monitoring of IL-1ß with a limit of detection of 4.7 pg mL-1, and a linear detection range of 12.5-200 pg mL-1. Good specificity and selectivity for monitoring of IL-1ß in rat macrophage secretion were achieved. Furthermore, this device was validated by detection of IL-1ß in rat whole blood samples with greater concentrations observed in obese rats compared to control, and strong positive correlation between concentrations of IL-1ß and blood glucose. These results suggest this device is feasible for direct detection of target analytes in biological samples.

Potassium control in chronic kidney disease: implications for neuromuscular function.

In Australia, approximately 1.7 million adults have evidence of chronic kidney disease (CKD). This complex disease can result in a multitude of complications, including hyperkalaemia, which is common and well recognised. The advent of new therapeutics aimed at lowering serum potassium has raised the possibility of optimising potassium control to enable greater use of renin-angiotensin-aldosterone system inhibitors in the management of CKD. Recent studies suggest that hyperkalaemia also has implications for peripheral neuropathy in CKD, a complication that substantially contributes to patient morbidity. This review examines evidence of the relationship between potassium and peripheral neuropathy, with a discussion of clinical implications. We searched PubMed for original and review articles using pre-specified key words, clinical guidelines and population data. The major findings were that contemporary CKD cohorts demonstrate a high prevalence of peripheral neuropathy, even in stage 3-4 CKD, including those without diabetes. The severity of the problem has been emphasised by an ominous rise in foot complications and amputation rates in dialysis patients, highlighting the need for increased awareness of the condition in earlier stages of CKD and targeted treatment strategies. It is likely that the pathophysiology of peripheral neuropathy in CKD is multifaceted, with potential influences from potassium, vascular abnormalities, diabetes, inflammation and unknown middle molecules. Despite these complexities, the relationship between potassium and nerve function in dialysis has been well established, and recent research in stage 3-4 CKD suggests that assertive potassium control may improve neuromuscular outcomes in CKD. These small studies should be confirmed in large, multicentre settings.

The utility of the Total Neuropathy Score as an instrument to assess neuropathy severity in chronic kidney disease: A validation study.

OBJECTIVE: To demonstrate construct validity of the Total Neuropathy Score (TNS) in assessing peripheral neuropathy in subjects with chronic kidney disease (CKD). METHODS: 113 subjects with CKD and 40 matched controls were assessed for peripheral neuropathy using the TNS. An exploratory factor analysis was conducted and internal consistency of the scale was evaluated using Cronbach's alpha. Construct validity of the TNS was tested by comparing scores between case and control groups. RESULTS: Factor analysis revealed valid item correlations and internal consistency of the TNS was good with a Cronbach's alpha of 0.897. Subjects with CKD scored significantly higher on the TNS (CKD: median, 6, interquartile range, 1-13; controls: median, 0, interquartile range, 0-1; p < 0.001). Subgroup analysis revealed construct validity was maintained for subjects with stages 3-5 CKD with and without diabetes. CONCLUSIONS: The TNS is a valid measure of peripheral neuropathy in patients with CKD. SIGNIFICANCE: The TNS is the first neuropathy scale to be formally validated in patients with CKD.

In Vivo Electrophysiological Measurement of the Rat Ulnar Nerve with Axonal Excitability Testing.

Electrophysiology enables the objective assessment of peripheral nerve function in vivo. Traditional nerve conduction measures such as amplitude and latency detect chronic axon loss and demyelination, respectively. Axonal excitability techniques "by threshold tracking" expand upon these measures by providing information regarding the activity of ion channels, pumps and exchangers that relate to acute function and may precede degenerative events. As such, the use of axonal excitability in animal models of neurological disorders may provide a useful in vivo measure to assess novel therapeutic interventions. Here we describe an experimental setup for multiple measures of motor axonal excitability techniques in the rat ulnar nerve. The animals are anesthetized with isoflurane and carefully monitored to ensure constant and adequate depth of anesthesia. Body temperature, respiration rate, heart rate and saturation of oxygen in the blood are continuously monitored. Axonal excitability studies are performed using percutaneous stimulation of the ulnar nerve and recording from the hypothenar muscles of the forelimb paw. With correct electrode placement, a clear compound muscle action potential that increases in amplitude with increasing stimulus intensity is recorded. An automated program is then utilized to deliver a series of electrical pulses which generate 5 specific excitability measures in the following sequence: stimulus response behavior, strength duration time constant, threshold electrotonus, current-threshold relationship and the recovery cycle. Data presented here indicate that these measures are repeatable and show similarity between left and right ulnar nerves when assessed on the same day. A limitation of these techniques in this setting is the effect of dose and time under anesthesia. Careful monitoring and recording of these variables should be undertaken for consideration at the time of analysis.

Effects of hemodialysis on intraneural blood flow in end-stage kidney disease.

INTRODUCTION: We quantified intraneural blood flow (INBF) in 18 patients with end-stage kidney disease (ESKD) and examined its relationship with nerve size, neuropathy severity, and nerve excitability parameters. METHODS: Sonographic measurements of the median nerve were performed at the same site before and after hemodialysis. INBF was quantified by analyzing power Doppler sonograms to obtain the vessel score (VSc) and maximum perfusion intensity (MPI). Corresponding median motor nerve excitability studies were performed. Neuropathy severity was assessed using Total Neuropathy Score. RESULTS: A total of 39% of ESKD patients had detectable INBF compared with none in the control group (P < 0.0001). Patients with detectable INBF had larger nerves and more severe neuropathy (P < 0.01). INBF parameters were significantly reduced after a session of dialysis (VSc: P < 0.01; MPI: P < 0.01). A significant relationship was found between interdialytic change in INBF and changes in nerve excitability. CONCLUSIONS: Increased INBF is a potential marker for neuropathy severity in ESKD patients. Muscle Nerve 57: 287-293, 2018.

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

BACKGROUND AND OBJECTIVES: Neuromuscular complications are almost universal in CKD by the time that a patient commences dialysis. Recent studies have indicated that chronic hyperkalemia may contribute to the development of neuropathy in CKD. This study was undertaken to determine whether dietary restriction of potassium intake may be a neuroprotective factor in CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A 24-month prospective, single-blind, randomized, controlled trial was undertaken in 47 consecutively recruited patients with stages 3 and 4 CKD. The intervention arm (n=23) was prescribed a diet focusing on potassium restriction to meet a monthly serum potassium level of ≤4.5 mEq/L, with oral sodium polystyrene sulfonate provided if dietary advice failed to achieve the target. The control arm (n=24) received dietary advice regarding general nutrition. The primary outcome was the change in the total neuropathy score evaluated by a blinded observer. Secondary outcomes included electrolyte levels, gait speed, neurophysiologic parameters, and health-related quality of life scores. Five patients withdrew before initiation of treatment, and final analysis consisted of n=21 in each group. RESULTS: There was a greater increase in total neuropathy score from baseline to final assessment in the control arm compared with the intervention arm (6.1±6.2-8.6±7.9 controls; 7.8±7.4-8.2±7.5 intervention; change 2.8±3.3-0.4±2.2, respectively; P<0.01). The intervention significantly reduced mean serum potassium compared with controls (4.6±0.1-4.8±0.1 mEq/L mean recorded every 6 months over the trial duration; P=0.03). There were no adverse changes in other nutritional parameters. Improved gait speed was also noted in the intervention arm compared with the control arm, with a mean increase of 0.15±0.17 m/s in the intervention group versus 0.02±0.16 m/s in the control group (P=0.01). CONCLUSIONS: Our results provide important preliminary evidence that dietary potassium restriction confers neuroprotection in CKD and should be confirmed in a larger multicenter trial.

The Effect of Diabetes on Cortical Function in Stroke: Implications for Poststroke Plasticity.

Diabetes may impair the capacity for neuroplasticity such that patients experience a slower and poorer recovery after stroke. The current study investigated changes in cortical function in stroke patients with diabetes to determine how this comorbidity may affect poststroke cortical plasticity and thereby functional recovery. From a cohort of 57 participants, threshold-tracking transcranial magnetic stimulation was used to assess cortical function over the ipsilateral and contralesional hemispheres in 7 patients with diabetes after an acute stroke compared with 12 stroke patients without diabetes. Cortical function was also assessed in 8 patients with diabetes without stroke and 30 normal control subjects. After acute stroke, short-interval intracortical inhibition (SICI) was reduced over both motor cortices in stroke patients without diabetes compared with normal control patients, while in stroke patients with diabetes, SICI was only reduced over the contralesional but not the ipsilesional cortex compared with control patients with diabetes. In addition, SICI was significantly reduced in the control patients with diabetes compared with normal control patients. These results have demonstrated the absence of ipsilesional cortical excitability change after diabetic strokes, suggesting impaired capacity for neuroplasticity over this hemisphere as a consequence of a "double-hit" phenomenon because of preexisting alterations in cortical function in nonstroke patients with diabetes. The reliance on reorganization over the contralesional cortex after stroke will likely exert influence on poststroke recovery in patients with diabetes.