Beneficial impact of spironolactone in diabetic nephropathy.
BACKGROUND
Aldosterone has been suggested to play a role in the initiation and progression of diabetic nephropathy. Currently recommended treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers [renin-angiotensin system (RAS) blockade] does not suppress circulating aldosterone sufficiently. We therefore aimed to evaluate the short-term effect of aldosterone antagonism with spironolactone on albuminuria and blood pressure in diabetic nephropathy.


METHODS
Twenty Caucasian type 1 diabetic patients with persistent macroalbuminuria despite antihypertensive treatment, including RAS blockade, completed this double-masked, randomized cross-over trial. Patients were treated in random order with spironolactone 25 mg once daily and matched placebo for two months, respectively, on top of usual antihypertensive treatment. After each treatment period albuminuria, 24-hour blood pressure, and glomerular filtration rate (GFR) were determined.


RESULTS
Spironolactone on top of usual antihypertensive treatment induced a 30% (95% CI 17 to 41) reduction in albuminuria from [geometric mean (95% CI)] 831 (624 to 1106) mg/24-hour on placebo treatment (P < 0.001), and a reduction in fractional albumin clearance of 35% (20 to 46, P < 0.001). Twenty-four-hour blood pressure showed an insignificant reduction of [mean reduction (95% CI)] 8 (-1 to 17)/3 (-0.2 to 7) mm Hg (P < 0.10). There was an insignificant reversible reduction in GFR during treatment with spironolactone. On spironolactone treatment, one patient was excluded due to hyperkalemia (plasma potassium 5.7 mmol/L) and one due to orthostatic dizziness. Otherwise treatment was well tolerated.


CONCLUSIONS
Our results suggest that spironolactone treatment on top of recommended antihypertensive treatment reduces blood pressure and may offer additional renoprotection in type 1 diabetic patients with diabetic nephropathy.
Schjoedt
Katrine Jordan
KJ
Steno Diabetes Center, Gentofte, Denmark. kjos@steno.dk
Rossing
Kasper
K
Juhl
Tina Ragnholm
TR
Boomsma
Frans
F
Rossing
Peter
P
Tarnow
Lise
L
Parving
Hans-Henrik
HH
D000328:Adult; D000450:Aldosterone / Q000097:blood; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D005260:Female; D006801:Humans; D006977:Hypertension, Renal / Q000188:drug therapy*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D013148:Spironolactone / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000450:Aldosterone