Abstract 5821: The Effect of Spironolactone on Biomarkers of Inflammation and Extracellular Remodelling in Early Chronic Kidney Disease
Introduction Early stage chronic kidney disease (CKD) is associated with major abnormalities of arterial and ventricular stiffness and function and with a high rate of adverse cardiovascular events. We have previously demonstrated that in this high risk group, significant reductions in LV mass and markers of arterial stiffness occurred after 40 weeks of treatment with the aldosterone antagonist, spironolactone. We hypothesized that serological markers of collagen turnover, inflammation and ventricular stress might also be improved with this treatment.
Methods 112 patients participating in the double blind randomized controlled trial investigating the effect of spironolactone in early CKD had serum biomarkers of
collagen turnover; amino-terminal propeptide of procollagen type III (PNIIIP),
inflammation; high sensitivity C-Reactive Protein (hsCRP), and
ventricular stress- N-terminal Pro Beta- Natriuretic Peptide (BNP) measured. Patients had stage 2 and 3 CKD, were on ACE Inhibitor or ARB therapy, with controlled hypertension (<130/85mmHg) and no history of cardiovascular disease or diabetes. Samples were measured at baseline and after 40 weeks of blinded treatment with either spironolactone 25mg once a day or matching placebo.
Results PNIIIP levels were unchanged with spironolactone but increased significantly in the placebo group (0.06μg/L±0.70 vs 0.46μg/L±0.82, p<0.01). There was no difference in median hsCRP levels (0.01mg/L (IQR 1.63) vs. 0.08mg/L (IQR 2.76), p =NS). Spironolactone resulted in significant reduction in median BNP levels (−0.4pg/L (IQR 70.9) vs. 9.3pg/L (IQR 54.7), p<0.01). All baseline biomarkers were positively correlated; PNIIIP with hsCRP (r = 0.24, p<0.05) PNIIIP and BNP (r = 0.27, p<0.01), hsCRP and BNP (r = 0.39, p<0.01).
Conclusion Treatment with spironolactone prevents deterioration of or improves biomarkers of collagen synthesis and of ventricular stress in CKD. These data support the hypothesis that deleterious effects of aldosterone on extracellular remodeling can be attenuated by spironolactone in CKD as has been observed in clinical outcome studies of heart failure. The association of all biomarkers suggests a complicated interplay of collagen turnover, inflammation and myocyte stretch.