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

Abstract

Background: Albuminuria persists in a substantial proportion of patients with diabetic kidney disease despite maximally tolerated renin-angiotensin system blockade, and aldosterone breakthrough is a recognised contributor to this residual risk. Conventional-dose mineralocorticoid receptor antagonism lowers proteinuria but carries an appreciable risk of hyperkalaemia, which limits its use in routine practice. This trial evaluated whether low-dose spironolactone added to standard care reduced proteinuria in diabetic kidney disease without unacceptable hyperkalaemia. Methods: A prospective, randomised, open-label, parallelgroup trial was conducted at a tertiary care teaching hospital. One hundred and twenty adults with type 2 diabetes mellitus, urine albumin-to-creatinine ratio 30 to 3000 mg/g, estimated glomerular filtration rate of at least 45 mL/min/1.73 m² and serum potassium not exceeding 5.0 mmol/L, all receiving maximally tolerated angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy, were randomised in a 1:1 ratio to spironolactone 12.5 mg once daily or to standard care alone for 24 weeks. The primary outcome was the percentage change in urine albumin-to-creatinine ratio from baseline to 24 weeks. Secondary outcomes were 24-hour urinary protein excretion, office blood pressure, estimated glomerular filtration rate, serum potassium and treatment-emergent adverse events. Results: Baseline characteristics were comparable between arms. At 24 weeks the median percentage change in urine albumin-to-creatinine ratio was −41.8% (interquartile range −56.2 to −24.6) with spironolactone and −4.2% (interquartile range −14.8 to +7.6) with standard care (p<0.001). A reduction of at least 30% was achieved by 41 of 60 participants (68.3%) versus 9 of 60 (15.0%) respectively (p<0.001). Systolic blood pressure fell by 9.6±8.2 mmHg versus 2.1±7.9 mmHg (p<0.001). The decline in estimated glomerular filtration rate did not differ significantly (−3.2±6.4 versus −1.2±6.1 mL/min/1.73 m²; p=0.082). Serum potassium rose by 0.29±0.34 versus 0.03±0.31 mmol/L (p<0.001), with potassium above 5.5 mmol/L in 6.7% versus 1.7% (p=0.36). Conclusion: Low-dose spironolactone added to maximally tolerated renin-angiotensin system blockade produced a clinically meaningful reduction in proteinuria over 24 weeks, accompanied by a modest and manageable rise in serum potassium.