However, recombinant ACE2 induced an increase in plasma ACE2 activity but did not affect urinary ACE2, and failed to protect mice against the development of DN, indicating that when the augmentation of ACE2 activity is limited to the circulation, it is not sufficient to provide renoprotection because ACE2 needs to reach the urinary space to be effective (Wysocki et al., 2017). This evidence concerns the gene ACE2 and liver dysplastic nodule.