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Beneficial Effects of Adding Spironolactone to Recommended Antihypertensive Treatment in Diabetic Nephropathy

A randomized, double-masked, cross-over study

¹ Steno Diabetes Center, Gentofte, Denmark
² Erasmus MC, Rotterdam, the Netherlands
³ Faculty of Health Science, University of Aarhus, Aarhus, Denmark

Address correspondence and reprint requests to Kasper Rossing, Steno Diabetes Center, Niels Steensens Vej 2, DK-2820 Gentofte, Denmark. E-mail: karo{at}steno.dk

OBJECTIVE—The objective of this study was to evaluate the safety and short-term effect of adding spironolactone to conventional antihypertensive treatment including diuretics and maximally recommended doses of an ACE inhibitor or an angiotensin II receptor blocker (ARB) on albuminuria and blood pressure in type 2 diabetic patients with nephropathy.

RESEARCH DESIGN AND METHODS—Twenty-one type 2 diabetic patients with nephropathy were enrolled in a randomized, double-masked, cross-over study. Patients were treated in random order with spironolactone 25 mg once daily and matched placebo for 8 weeks, respectively, in addition to ongoing antihypertensive treatment including diuretics and maximally recommended doses of an ACE inhibitor and/or an ARB. At the end of each treatment period, albuminuria, 24-h ambulatory blood pressure (ABP), and glomerular filtration rate (GFR) were determined.

RESULTS—During the addition of placebo, values were as follows: albuminuria (geometric mean [range]) 1,566 [655–7,762] mg/24 h, ABP (mean ± SE) 138 ± 3/71 ± 1 mmHg, and GFR (mean ± SE) 74 ± 6 ml/min per 1.73 m². During the addition of spironolactone, albuminuria was reduced by 33% (95% CI 25–41) (P < 0.001), fractional clearance of albumin by 40% (24–53) (P < 0.001), and 24-h ABP by 6 mmHg (2–10) for systolic and 4 mmHg (2–6) for diastolic (P < 0.001 for both). The change in albuminuria did not correlate with the change in systolic 24-h ABP (r = 0.19, P = 0.42) or diastolic 24-h ABP (r = 0.01, P = 0.96). Spironolactone treatment induced an insignificant reversible reduction in GFR of 3 ml/min per 1.73 m² (–0.3 to 6) (P = 0.08). One patient was excluded from the study due to hyperkalemia. Otherwise treatment was well tolerated.

CONCLUSIONS—Our study suggests that spironolactone safely adds to the reno- and cardiovascular protective benefits of treatment with maximally recommended doses of ACE inhibitor and ARB by reducing albuminuria and blood pressure in type 2 diabetic patients with nephropathy.

Abbreviations: ABP, ambulatory blood pressure • ARB, angiotensin II receptor blocker • GFR, glomerular filtration rate • RAAS, renin-angiotensin-aldosterone system

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