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. 2024 Dec 14;7(1):37-46.
doi: 10.1253/circrep.CR-24-0142. eCollection 2025 Jan 10.

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

Takashi Kitao  1 , Eriko Konishi  1 , Noriaki Itoh  1 , Ayumu Hirata  2
Affiliations

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

Takashi Kitao et al. Circ Rep. .

Abstract

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.

Keywords: Albuminuria; Esaxerenone; Hypertension; Prognosis; Proteinuria.

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Conflict of interest statement

The authors have no financial conflicts of interest to disclose concerning this manuscript.

Figures

Figure 1.
Figure 1.
(A) Proteinuria severity classification in the modified Kidney Disease: Improving Global Outcomes (KDIGO) 2012 Chronic Kidney Disease (CKD) Guideline for the Japanese population. (B) Study flowchart. UACR, urinary albumin-to-creatinine ratio; UPCR, urinary protein-to-creatinine ratio.
Figure 2.
Figure 2.
Changes in proteinuria severity classification from baseline to 6 months following esaxerenone initiation.
Figure 3.
Figure 3.
Kaplan-Meier curves and log-rank test for the primary endpoint in subgroups. (A) Subgroups classified according to proteinuria severity classification at baseline. (B) Subgroups reclassified and subdivided according to proteinuria severity classification 6 months following esaxerenone initiation. P value is the result of the log-rank test.
Figure 4.
Figure 4.
Kaplan-Meier curves and log-rank test for cardiovascular or renal events in subgroups reclassified and subdivided according to proteinuria severity classification 6 months following esaxerenone initiation. (A) Cardiovascular events. (B) Renal events. P value is the result of the log-rank test.
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