van den Meiracker AH et al. (2006) Spironolactone in type 2 diabetic nephropathy: effects on proteinuria, blood pressure and renal function. J Hypertens 24: 2285–2292

Drugs that interfere with the renin–angiotensin system can provide renoprotection in patients with diabetic nephropathy, possibly by exerting an antiproteinuric effect. Aldosterone might have a role in the progression of renal disease; therefore, van den Meiracker et al. investigated whether adding the aldosterone receptor antagonist spironolactone to renin–angiotensin system inhibition improved proteinuria in patients with diabetic nephropathy.

Patients with type 2 diabetes and macroalbuminuria despite use of an angiotensin-converting-enzyme inhibitor or an angiotensin-receptor blocker for ≥1 year were randomized to spironolactone (n = 29) or placebo (n = 30) 25–50 mg daily for 1 year. Five patients taking spironolactone and one patient on placebo developed hyperkalemia within 2–12 weeks of initiation of study medication and were excluded.

After 1 year, urinary protein:creatinine and urinary albumin:creatinine ratios decreased markedly in patients treated with spironolactone but did not change in those receiving placebo. Decreases in systolic and diastolic blood pressures were seen in patients treated with spironolactone, but no changes were noted in placebo-treated patients. Estimated glomerular filtration rate decreased in both groups, but the average decrease after 1 year was greater in the spironolactone group (P = 0.004). Increases in serum potassium levels, however, were seen in spironolactone-treated but not placebo patients. Urinary protein:creatinine and urinary albumin:creatinine ratios decreased with decreasing estimated glomerular filtration rate.

The authors conclude that adding spironolactone to an angiotensin-converting-enzyme inhibitor or an angiotensin-receptor blocker reduces proteinuria throughout 1 year of treatment; they add that the initial daily dose should be ≤25 mg to reduce the risk of hyperkalemia.