Effects of Spironolactone in Combination with Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers in Patients with Proteinuria

Abstract

Background/Aims: This study aimed to investigate the potential beneficial anti-proteinuric effect of an add-on aldosterone blockade and the impact of the aldosterone escape phenomenon. Methods: We retrospectively analyzed data of 304 patients with persistent proteinuria, who were administered spironolactone (25 mg/day) after treatment with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) for >3 months. Patients were divided according to their aldosterone levels during ACEI/ARB treatment into an escape group (plasma aldosterone >80 pg/mL, N=95, 31.5%) and a non-escape group (plasma aldosterone ≤80 pg/mL, N=209, 68.5%) and according to their urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). Results: After 12 months, the UACR decreased significantly in patients with 1≤UACR<3.5 g/g Cr, UACR ≥3.5 g/g Cr, and eGFR ≥60 mL/min/1.73 m², and in the non-escape group. Severe hyperkalemia (K≥7.0 mEq/L) developed in 9 of 137 patients with eGFR<60 mL/min/1.73 m² (6.5%) and in none of the 167 patients with eGFR≥60 mL/min/1.73 m². Conclusions: Proteinuria decreased significantly after add-on spironolactone treatment in patients with 1≤UACR<3.5 g/g Cr, UACR ≥3.5 g/g Cr, and eGFR ≥60 mL/min/1.73 m², and in the non-escape group. The anti-proteinuric effect of spironolactone may vary according to the degree of albuminuria, impaired eGFR, and aldosterone escape.