Experimental studies suggest a detrimental role for cyclic adenosine monophosphate (cAMP) and vasopressin in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). It is unknown, however, whether urinary cAMP and copeptin concentration are associated with disease severity in patients with ADPKD. Urinary cAMP (u-cAMP) and copeptin concentration (u-copeptin) were measured by immunoassay in ADPKD patients with CKD stage ≤4. We compared our measurements with clinical parameters including estimated glomerular filtration rate (eGFR), total kidney volume (TKV), and height-adjusted TKV (htTKV). Logarithmic transformation of all variables was performed to fulfill the requirement of equal distribution of the residuals. We included 50 patients in this study (24 females and 26 males; mean age: 49.3 years). The median eGFR and TKV were 53.2 ml/min/1.73 m(2) (interquartile range: IQR; 29.4-68.45) and 1138.1 ml (IQR; 814.7-2065.0), respectively. The median u-copeptin level was 12.19 (IQR; 6.91-22.32) ng/ml. Although u-cAMP/u-Cr was not significantly correlated with TKV (R = -0.006, p = 0.967) and eGFR (R = 0.077, p = 0.602), urinary copeptin/u-Cr was statistically associated with the various markers of disease severity in ADPKD [positively with TKV (R = 0.351, p = 0.014), htTKV (R = 0.383, p = 0.008) and negatively with eGFR (R = -0.304, p = 0.036)]. In ADPKD subjects, a higher u-copeptin is associated with disease progression, suggesting that u-copeptin may be a new surrogate marker to predict renal prognosis in ADPKD.