ALT Determinants of HRS-1 reversal. (1) Timing of initiation—the earlier in the disease evolution (i.e., at lower stages of AKI), the greater the likelihood of response to therapy. (2) Effect on mean arterial pressure (MAP). There is a nearly linear correlation between the increase in MAP and the likelihood of HRS-1 reversal. Although the ideal MAP target is not clear, an increase of ≥15 mm Hg has been associated with improved outcomes. (3) The degree of underlying liver disease. Patients with an elevated total bilirubin level are less likely to respond to therapy; whether this is a direct effect of bile acid nephrotoxicity or a reflection of the underlying severity of illness is not known. (4) Reversal of the trigger. Whether infection, hemorrhage, or other trigger, removal and treatment of the trigger dictate clinical outcomes. (5) Underlying CCM or PoPHTN plays an important role in determining if a patient will respond to vasoconstrictor therapy and have HRS-1 reversal.