Clinical assumptions
albuminuria
Several mechanisms may explain the renoprotective effect of esaxerenone. First, esaxerenone primarily reduces BP, which then leads to a reduction in glomerular pressure, and it can also reduce urinary albumin excretion. Second, esaxerenone may directly affect renal function and may also affect urinary albumin excretion. In addition to these mechanisms, esaxerenone may have other effects on albuminuria suppression.Based on these clinical assumptions, we considered SBP and eGFR as mediators that reflect the changes in BP and renal function and assumed the following causal relationships between the variables in this analysis (Fig. Causal relationships between variables. The graph displays the assumptions about causal relationships between variables. If an arrow points away from X and toward Y, it indicates that X causally affects YThe values of SBP and eGFR change longitudinally during treatment. In addition, SBP and eGFR may affect UACR changes in different manners. Therefore, to incorporate the changes in SBP and eGFR during treatment, two types of mediator variables were considered: the cumulative average value of change from baseline up to the end of treatment and the achieved value of change from baseline to just before the end of treatment. The former assumes a cumulative effect, and the latter assumes an acute effect of mediator variables on the outcome.