Verification of the Impact of Changes in the Severity Classification of Proteinuria on the Prognosis of Hypertensive Patients Following the Initiation of Esaxerenone

Background: The urinary albumin-to-creatinine ratio (UACR) or urinary protein-to-creatinine ratio (UPCR) has been reported as predictors of cardiovascular and renal events. We aimed to evaluate the impact of changes in proteinuria severity on the prognosis of hypertensive patients post-esaxerenone initiation. Methods and Results: Hypertensive patients who commenced esaxerenone (n=164) were classified into 3 groups according to baseline UACR or UPCR, based on the modified proteinuria severity classification: A1 (normal; n=35); A2 (microalbuminuria/mild proteinuria; n=49); and A3 (macroalbuminuria/severe proteinuria; n=80). At 6 months post-esaxerenone initiation, these patients were then reclassified into 3 groups: Á1 (n=48); Á2 (n=66); and Á3 (n=50). Á2 was further subdivided into 2 groups: Á2a (n=34); and Á2b (n=32), the latter representing patients who improved from A3. The primary endpoint was defined as the composite of cardiovascular and renal death, heart failure hospitalization, non-fatal myocardial infarction, initiation of dialysis, and estimated glomerular filtration rate decline exceeding 40%. Severity of proteinuria improved significantly after 6 months (P=0.003). The incidence of the primary endpoint was significantly higher in Á3 compared with Á1 (log-rank P<0.001); however, no significant difference was observed between Á1 and Á2b (log-rank P=0.12). Conclusions: Esaxerenone may ameliorate proteinuria severity and improve the prognosis of patients with macroalbuminuria or severe proteinuria.