UNLABELLED: 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. MATERIALS AND 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 withangiotensin-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. OUTCOME MEASURES: 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. DISCUSSIONS: 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.
RCT Entities:
UNLABELLED: 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. MATERIALS AND METHODS: The studies were double-blind, randomised, placebo-controlled studies in 46 type 1 and 23 type 2 diabeticpatients 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. OUTCOME MEASURES: 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. DISCUSSIONS: 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: Ruan Kruger; Rudolph Schutte; Hugo W Huisman; Peter Hindersson; Michael H Olsen; Jesper Eugen-Olsen; Aletta E Schutte Journal: PLoS One Date: 2013-03-13 Impact factor: 3.240
Authors: N Muñoz-Durango; A Vecchiola; L M Gonzalez-Gomez; F Simon; C A Riedel; C E Fardella; A M Kalergis Journal: Biomed Res Int Date: 2015-09-10 Impact factor: 3.411
Authors: Natalia Muñoz-Durango; Cristóbal A Fuentes; Andrés E Castillo; Luis Martín González-Gómez; Andrea Vecchiola; Carlos E Fardella; Alexis M Kalergis Journal: Int J Mol Sci Date: 2016-06-23 Impact factor: 5.923