Spironolactone prevents renal fibrosis due to hypertension

The use of spironolactone provides protective benefits against hypertension-induced renal fibrosis by promoting autophagy and preventing the activation of NLRP3 inflammasome, according to a study.

Treatment with spironolactone 20 mg/kg/day was effective in maintaining systolic blood pressure and renal function. This was made possible by significantly reducing aldosterone and testosterone levels.

Hypertension-induced renal fibrosis was predominant in the glomeruli, tubules, and interstitium. It also correlated with autophagy inhibition in renal tubules, NLRP3 inflammasome activation, both M1 and M2 macrophages polarization, with a predominant effect on M1 polarization, decreased CD4+ T cell population and CD4/CD8 ratio, and increased CD8+ T cell and dendritic cell population.

Autophagy was responsible for the negative regulation of the NLRP3 inflammasome. With the use of spironolactone, both M1 and M2 macrophages polarization were suppressed. It also reduced CD8+ T and dendritic cell population, increased CD4+ T cell population, negatively regulated the release of NLRP3 inflammasome-related proteins in macrophages, and restored autophagy in the glomeruli and renal tubules.

“Spironolactone acts on sites where the mineralocorticoid receptor is present,” the investigators said. “A dose of 20-mg/kg/day spironolactone is well tolerated and protects against hypertension-induced renal fibrosis by restoring autophagy and suppressing NLRP3 inflammasome activation.”

In this study, the investigators performed in-vivo and in-vitro experiments. They assessed renal function and serum potassium, estradiol, testosterone, and plasma aldosterone levels, together with autophagy indicators LC3 and p62, and NLRP3 inflammasome-related proteins (NLRP3, Caspase-1, IL-1β, and IL-18). 

In addition, the authors examined changes in macrophage polarization and T cell and dendritic cell populations.