Effect of Low-Dose Spironolactone on Proteinuria in Diabetic Kidney Disease — A Randomized Controlled Trial

Abstract

Background: Residual proteinuria persists in many diabetic kidney disease patients despite maximal renin-angiotensin-aldosterone system blockade with ACE inhibitors or angiotensin receptor blockers. Low-dose spironolactone has been proposed as an adjunctive antiproteinuric agent targeting aldosterone-mediated renal injury. Methods: A double-blind placebo-controlled randomized trial was conducted from March 2022 to April 2023. Ninetysix patients with diabetic kidney disease and persistent proteinuria (urine protein-creatinine ratio above 0.5 g/g) despite maximal ACE inhibitor or ARB therapy for at least 3 months were randomized to receive spironolactone 25 mg daily (n equals 48) or matching placebo (n equals 48) for 24 weeks. The primary endpoint was percentage change in UPCR from baseline. Secondary endpoints included change in eGFR, blood pressure, and serum potassium. Results: Mean baseline UPCR was 1.82 plus or minus 0.86 in the spironolactone group and 1.78 plus or minus 0.92 g/g in the placebo group. At 24 weeks, spironolactone reduced UPCR by 34.2% versus 8.6% with placebo (p less than 0.001). Mean absolute UPCR reduction was 0.62 plus or minus 0.38 versus 0.16 plus or minus 0.24 g/g (p less than 0.001). eGFR remained stable in both groups (change minus 1.2 versus minus 2.4 mL/min, p equals 0.286). Systolic BP decreased more with spironolactone (minus 8.4 versus minus 3.2 mmHg, p equals 0.006). Hyperkalaemia above 5.5 mEq/L occurred in 12.5% versus 2.1% (p equals 0.048) but none exceeded 6.0 mEq/L or required discontinuation. Conclusion: Lowdose spironolactone at 25 mg daily significantly reduced proteinuria by 34% in diabetic kidney disease patients with residual proteinuria on maximal RAAS blockade. The treatment was well-tolerated with manageable hyperkalaemia risk. Regular potassium monitoring is recommended.