PURPOSE: Renin-angiotensin system hyperactivation in autosomal-dominant polycystic kidney disease (ADPKD) patients leads to early hypertension. Cystic enlargement probably causes parenchymal hypoxia, renin secretion, and endothelial dysfunction. Sympathetic and parasympathetic balance is altered in this condition, especially during the night, also affecting blood pressure circadian rhythm. Aim of this study was to evaluate sympathetic/parasympathetic balance using heart rate variability (HRV) parameters and find a correlation between HRV and renal damage progression, as total kidney volume enlargement, in ADPKD patients. METHODS: Sixteen adult ADPKD patients were enrolled in the study. Eleven patients (68.8%) were male, and the median age was 42 years (IQR 36-47.5). HRV parameters were calculated using 24 h-ECG Holter. A kidney magnetic resonance imaging (MRI) scan 3 Tesla was performed to evaluate total kidney volume (TKV) and total fibrotic volume (TFV). RESULTS: A statistically significant positive linear correlation was observed between length of kidneys and frequency domain parameters as low frequency (LF) (r = 0.595, p < 0.05) and LFday (r = 0.587, p < 0.05). Moreover, a statistically significant positive linear correlation exists between high frequency (HF) and TFV (r = 0.804, p < 0.01) or height-adjusted (ha) TFV (r = 0.801, p < 0.01). Finally, we found a statistically significant positive linear correlation between HFnight and TKV (r = 0.608, p < 0.05), ha-TKV (r = 0.685, p < 0.01), TFV (r = 0.594, p < 0.05), and ha-TFV (r = 0.615, p < 0.05). CONCLUSION: We suppose that the increase in TKV and TFV could lead to a parasympathetic tone hyperactivation, probably in response to hypoxic stress and vasoconstriction due to cystic enlargement.