The Role of Serum Potassium in Uremic Peripheral Neuropathy: A comparative study between CKD stage 3-4 and stage 5

By Elda CULE, Merita RROJI

Abstract
Background and objectives: Uremic peripheral neuropathy (UPN) is a frequent and disabling complication of chronic kidney disease (CKD), particularly in its advanced stages. The condition arises through multiple mechanisms, including the accumulation of uremic toxins, oxidative stress, and metabolic derangements.
However, the contribution of electrolyte imbalances, especially disturbances in serum potassium, has received comparatively little attention. Hyperkalemia is common in CKD, and experimental data suggest that elevated extracellular potassium may depolarize axons and exacerbate neuropathic dysfunction. This study aimed to explore the relationship between serum potassium levels and neuropathy severity in patients with moderate-to-advanced CKD.
Methods: This is a cross-sectional analysis of 63 non-diabetic adults with confirmed CKD, of whom 57% were in stages 3–4 and 33% in stage 5 (non-dialysis). Peripheral neuropathy was defined according to established literature as an MNSI score greater than seven and/or abnormal findings on nerve conduction studies (NCS), consistent with diagnostic thresholds used in prior epidemiological and clinical studies of CKD related neuropathy. Neuropathy assessment was conducted within 24 hours of serum potassium measurement. Descriptive statistics, group comparisons, correlation testing, and multivariate regression analyses were applied.
Results: The mean age of participants was 65.1 years; 33% females. UPN was more prevalent and severe in stage 5 patients, with 63% recording an MNSI score >7 compared with 27% of those in stages 3–4 (p<0.001). Serum potassium levels were significantly higher in stage 5 patients compared with those in stages 3–4 (5.1 ± 0.6 vs. 4.75 ± 0.5 mmol/L, p =0.026). A moderate positive correlation was found between serum potassium levels and MNSI scores (r = 0.48, p <0.03). Multivariate regression analysis demonstrated that both potassium (β = +0.87, p = 0.013) and eGFR (β = –0.02, p = 0.049) were independent predictors of neuropathy severity,together accounting for 32% of the observed variance (R² = 0.32).
Conclusion: Elevated serum potassium is independently associated with increased severity of UPN in CKD, especially in stage 5 disease. The observed relationship supports experimental evidence connecting hyperkalemia to axonal depolarization and indicates that potassium imbalance may accelerate neuropathic changes even in earlier CKD stages. These findings highlight the importance of vigilant potassium
monitoring and early correction of abnormalities as potentially modifiable strategies to slow neuropathy progression and enhance patient quality of life