Aim: End-stage renal disease (ESRD) patients requiring hemodialysis (HD) treatment experience rapid blood electrolyte fluctuations that can trigger ventricular repolarization instability, increasing arrhythmia vulnerability and cardiovascular risk. T-wave alternans (TWA) may serve as a non-invasive marker of such instability. In this work, we assessed the correlation between TWA amplitude and variations in serum potassium [K+] and calcium [Ca2+] concentration levels in ESRD patients during an HD session. Methods: A total of 29 48-hour Holter ECGs from ESRD patients (12 leads, sampling frequency 1000 Hz), including a complete HD session together with a set of synchronous hourly-collected blood samples (before, 3 during the HD and at the end of the session), were analyzed. The index of median alternans (IMA), quantifying the average absolute TWA amplitude, was measured in consecutive 1 hour intervals using a fully automated method based on periodic component analysis (πCA) and the Laplacian likelihood method. Intrapatient Pearson's correlation coefficient (r) between IMA and both [K+] and [Ca2+] ionic concentrations along the HD session was assessed. Results: Analysis of the temporal evolution of IMA during the HD demonstrated a direct correlation with [K+] variations, and yielded a result of (median [Q1,Q3]) r = 0.79 [0.32,0.91] (Fig. 1a). Moreover, variations in [Ca2+] level showed an inverse association with IMA with r = -0.59 [-0.82,-0.08] (Fig. 1b). Conclusion: TWA amplitude, measured by IMA, is responsive to the rapid intradialytic fluctuations of serum [K+] and [Ca2+]. Since these electrolyte shifts directly drive repolarization instability, IMA emerges as a promising non-invasive biomarker for real-time monitoring of arrhythmic risk in ESRD patients.