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Introduction: Peripheral neuropathy is common in chronic kidney disease (CKD) and may be multifactorial in origin, resulting from uremia, hyperkalemia, and diabetes. Previous studies have suggested that magnesium plays a crucial role in chronic pain. Studies evaluating magnesium in neuropathy have demonstrated mixed results. Aims: To provide preliminary data on the effectiveness of transdermal magnesium in treating peripheral neuropathy related to CKD. Methods: Twenty participants with advanced CKD were enrolled from a major teaching hospital clinic in Sydney, Australia. Each participant was provided with a spray bottle containing magnesium chloride and instructed to apply five sprays to each limb affected by neuropathy daily for 12 weeks. Participants completed the Neuropathy Total Symptom Score-6 (NTSS-6) every 4 weeks during follow-up. Serum magnesium concentrations were measured at 4-week intervals. Results: Twenty participants were recruited, of which 14 completed the 12-week follow-up period. Mean age was 78.90 years, 80.00% were female and mean estimated glomerular filtration rate was 9.78 mL/min/1.73 m2. With intention to treat analysis (mean [95% confidence interval]), NTSS-6 was significantly reduced at weeks 8 (4.04 [2.43–5.65]) and 12 (4.26 [2.47–6.05]), compared with baseline (6.92 [5.29–8.55]), p < 0.05. Serum magnesium concentration did not change significantly during the study. Conclusion: This pilot study suggests that transdermal magnesium may be beneficial in reducing frequency and severity of peripheral neuropathic symptoms in patients with advanced CKD. Trial Registration: australianclinicaltrials.gov.au. Identifier: ACTRN12621000841875. Date first registered January 7, 2021. [ABSTRACT FROM AUTHOR]