title: Levels of NT-proBNP, markers of low-grade inflammation, and endothelial dysfunction during spironolactone treatment in patients with diabetic kidney disease.
abstract: Renin-angiotensin-aldosterone system (RAAS) blockade may reduce levels of biomarkers of chronic low-grade inflammation and endothelial dysfunction. We investigated the effect of spironolactone added to standard RAAS blockade on these biomarkers in an analysis of four original studies.
  
  
  METHODS
  The studies were double-blind, randomised, placebo-controlled studies in 46 type 1 and 23 type 2 diabetic patients with micro- or macroalbuminuria treated with angiotensin-converting enzyme inhibitor (ACE inhibitor) or angiotensin receptor blocker (ARB), and randomised to additional treatment with spironolactone 25 mg and placebo daily for 60 days.
  
  
  METHODS
  Changes in inflammatory (hsCRP, s-ICAM, TNFα, IL-6, IL-8, Serum amyloid A, IL1β), endothelial dysfunction (sE-selectin, s-ICAM1, s-VCAM1, VWF, p-selectin, s-thrombomodulin) and NT-proBNP after each treatment period.
  
  
  RESULTS
  During spironolactone treatment, u-albumin excretion rate was reduced from 605 (411-890) to 433 (295-636) mg/24 h, as previously reported. Markers of inflammation and endothelial dysfunction did not change; only changes in NT-proBNP (reduced by 14%, p=0.05) and serum amyloid A (reduced by 62%, p=0.10) were borderline significant.
  
  
  CONCLUSIONS
  Our results indicate that the renoprotective effect of spironolactone when added to RAAS blockade is not mediated through anti-inflammatory pathways since markers of inflammation and endothelial dysfunction are not affected during treatment.
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark.
authors.forename: Stine E
authors.initials: SE
authors.lastname: Nielsen
authors.forename: Katrine J
authors.initials: KJ
authors.lastname: Schjoedt
authors.forename: Kasper
authors.initials: K
authors.lastname: Rossing
authors.forename: Frederik
authors.initials: F
authors.lastname: Persson
authors.forename: Casper G
authors.initials: CG
authors.lastname: Schalkwijk
authors.forename: Coen D A
authors.initials: CD
authors.lastname: Stehouwer
authors.forename: Hans-Henrik
authors.initials: HH
authors.lastname: Parving
authors.forename: Peter
authors.initials: P
authors.lastname: Rossing
mesh_terms: D000419:Albuminuria / Q000097:blood / Q000150:complications / Q000188:drug therapy; D015415:Biomarkers / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications / Q000188:drug therapy; D003928:Diabetic Nephropathies / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D004311:Double-Blind Method; D004727:Endothelium / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood*; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D013148:Spironolactone
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D013148:Spironolactone
keywords: Diabetes; diabetic nephropathy; endothelial dysfunction; inflammation