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.

Fampridine treatment and walking distance in multiple sclerosis: A randomised controlled trial.

OBJECTIVE: To explore the benefits of modified-release fampridine on walking distance in MS. METHODS: This was a randomised double-blind, placebo-controlled crossover trial of fampridine in 25 MS patients. The primary outcome measure was the six minute walk test (6MWT). A p-value<10% led to rejection of the null hypothesis. RESULTS: The pre-specified criterion for statistical significance was met, with a 17m improvement in 6MWT in the treatment arm. In addition, baseline S2 accommodation, a nerve excitability parameter that reflects slow K+ channel activity, modified the effect of fampridine. For patients who had abnormally high S2 accommodation values, there was a 28m improvement in the 6MWT (p=0.04). In contrast, for patients with low S2 values, a 0m improvement was noted (p=1.0). CONCLUSION: The study provides evidence that fampridine may improve walking distance. Nerve excitability assessment may be useful in selecting those patients who are most likely to gain benefit from fampridine. SIGNIFICANCE: Fampridine may improve walking distance in MS. Nerve excitability assessment may assist in identifying those patients most likely to respond to fampridine.

Effect of fampridine on axonal excitability in multiple sclerosis.

OBJECTIVE: To investigate the effects of fampridine on nerve excitability, the present study utilized peripheral axonal excitability techniques in 18 MS patients receiving treatment with fampridine. METHODS: Studies were performed at baseline and repeated 3months after institution of fampridine at standard dosing. RESULTS: Following treatment with fampridine there were significant changes in axonal excitability for those parameters associated with fast K(+) channels that shifted towards normal control values. Specifically, increases were noted in the peak superexcitability of recovery cycle (fampridine, -25.6±1.6%; baseline -22.8±1.7%; p<0.004), peak depolarizing threshold electrotonus (fampridine, 69.1±1.0%; baseline 67.0±1.4%; p<0.004), and depolarizing threshold electrotonus between 40 and 60ms after onset of depolarization (fampridine, 52.8±1.3%; baseline 49.9±1.4%; p=0.02). CONCLUSION: The present study has established that fampridine at standard doses exerts effects on peripheral nerve function that may be mediated by reduction of fast K(+) conductances. SIGNIFICANCE: Modulation of fast K(+) conductances by fampridine may contribute to the improvement observed in MS symptoms including motor fatigue.