Beneficial effects of adding spironolactone to recommended antihypertensive treatment in diabetic nephropathy: a randomized, double-masked, cross-over study.
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.


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.
Rossing
Kasper
K
Steno Diabetes Center, Niels Steensens Vej 2, DK-2820 Gentofte, Denmark. karo@steno.dk
Schjoedt
Katrine J
KJ
Smidt
Ulla M
UM
Boomsma
Frans
F
Parving
Hans-Henrik
HH
D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure; D015992:Body Mass Index; D003404:Creatinine / Q000097:blood; D018592:Cross-Over Studies; D003928:Diabetic Nephropathies / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004232:Diuretics / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011188:Potassium / Q000097:blood; D013148:Spironolactone / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D004232:Diuretics; D010919:Placebos; D013148:Spironolactone; D003404:Creatinine; D011188:Potassium