title: Beneficial impact of spironolactone on nephrotic range albuminuria in diabetic nephropathy.
abstract: Reduction of nephrotic range albuminuria is associated with markedly improved renal and cardiovascular outcome in patients with diabetic nephropathy. Aldosterone has been suggested to play a role in the progression of diabetic nephropathy. We therefore aimed to evaluate the short-term effect of aldosterone antagonism with spironolactone on nephrotic range albuminuria and blood pressure in diabetic nephropathy. Twenty Caucasian patients with diabetic nephropathy and nephrotic range albuminuria (>2500 mg/24 h) despite recommended antihypertensive treatment completed this double-masked, randomized crossover trial. Patients were treated in random order with spironolactone 25 mg once daily and matched placebo for 2 months, on top of ongoing antihypertensive treatment, including an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker in maximally recommended doses. Median (range) number of antihypertensive drugs was 3 (2-5). After each treatment period, albuminuria, 24-h ambulatory blood pressure, and glomerular filtration rate (GFR) were determined. Spironolactone on top of recommended renoprotective treatment induced a 32% (95% confidence interval (CI): 21-42%) reduction in albuminuria from (geometric mean (95% CI)) 3718 (2910-4749) mg/24 h on placebo treatment (P<0.001). There was a significant reduction in 24-h blood pressure of 6 (2-10)/4 (2-6) mm Hg and day blood pressure of 7 (3-12)/5 (3-7) mm Hg (P<0.01), whereas night blood pressure remained unchanged. Spironolactone induced an insignificant reversible reduction in GFR of 3 ml/min/1.73 m2 from 64 (27) ml/min/1.73 m2. No patients were excluded due to adverse events. Our results suggest that spironolactone treatment on top of recommended renoprotective treatment including maximal renin-angiotensin system blockade may offer additional renoprotection in patients with diabetic nephropathy and nephrotic range albuminuria.
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark. kjos@sterno.dk
authors.forename: K J
authors.initials: KJ
authors.lastname: Schjoedt
authors.forename: K
authors.initials: K
authors.lastname: Rossing
authors.forename: T R
authors.initials: TR
authors.lastname: Juhl
authors.forename: F
authors.initials: F
authors.lastname: Boomsma
authors.forename: L
authors.initials: L
authors.lastname: Tarnow
authors.forename: P
authors.initials: P
authors.lastname: Rossing
authors.forename: H-H
authors.initials: HH
authors.lastname: Parving
mesh_terms: D000328:Adult; D000419:Albuminuria / Q000188:drug therapy*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D018592:Cross-Over Studies; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D009401:Nephrosis / Q000188:drug therapy; D013148:Spironolactone / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone