Effect of Spironolactone for One Year on Endothelial Function and Vascular Inflammation Biomarkers in Renal Transplant Recipients.
BACKGROUND Kidney transplantation is associated with increased cardiovascular risk. Endothelial dysfunction and vascular inflammation contribute to negative outcome. In experimental models, mineralocorticoid receptor antagonists (MRA) improved endothelial function and reduced inflammation. The current study tested the hypothesis that the MRA spironolactone improves endothelial function and reduces vascular inflammation in renal transplant patients. METHODS 80 renal transplant patients from an ongoing, double blind randomized placebo controlled trial were included. Paired plasma samples before and after one year of treatment (n=39 in spironolactone group, n=41 in placebo group) were used to determine markers of endothelial dysfunction (nitrite, nitrate, cyclic guanosine monophosphate, arginine, citrulline, ornithine, asymmetric dimethylarginine, symmetric dimethylarginine, NG monomethyl L arginine, von Willebrand Factor, tissue type plasminogen activator antigen, plasminogen activator inhibitor 1 antigen) and markers of inflammation (intercellular adhesion molecule, vascular adhesion molecule, high sensitivity C reactive protein and serum amyloid protein A) RESULTS Spironolactone increased plasma aldosterone (p<0.001) and potassium (p<0.001) Blood pressure did not change significantly. No significant differences were detected between groups in any of the measured markers of endothelial dysfunction or inflammation except in the subgroup analysis of diabetes patients, where spironolactone decreased nitrite compared to placebo. CONCLUSIONS MR blockade did not improve biomarkers of endothelial dysfunction or vascular inflammation in renal transplant patients. Since no beneficial effect of MR blockade on vascular biomarkers was found, aldosterone is likely not a major promoter of vascular dysfunction in renal transplant patients.
American journal of physiology. Renal physiology