These data suggest that there is space for safer and tolerated best in class cAMP lowering approaches in ADPKD either targeting additional pathways regulating cAMP (PKA inhibition, PDE activation), biased V2R antagonists or combination with targets that may provide an additive or synergistic effect such as the calcium-sensing receptor (Di Mise et al., 2021; Zhou and Torres, 2022). Here, AVPR2 is linked to autosomal dominant polycystic kidney disease.