Antifibrotic Effects of Aldosterone Receptor Blocker (Spironolactone) in Patients with Chronic Kidney Disease

Abstract

Aims. Proteinuria and transforming growth factor β (TGF-β) are parameters that can lead to glomerulosclerosis and tubulointerstitial fibrosis. All components of the renin-angiotensin-aldosterone system (RAAS) activate the TGF-β. Aldosterone may not be inhibited with angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin receptor blockers (ARBs) due to aldosterone escape. We aimed to evaluate the effect of spironolactone on parameters leading to fibrosis. Methods. This prospective study included 30 non-diabetic chronic kidney disease (CKD) patients treated with ACEIs and/or ARBs. The patients were divided into two groups that are similar in terms of demographic parameters. 25 mg of spironolactone was added to group 1 (n = 15) for six months, though it was not administered to group 2 (n = 15). Creatinine (U-Cr), protein (U-Prot), and TGF-β1 (U- TGF-β1) were measured in spot urine sample in the beginning of study and six months later. Results. Twenty-four patients completed the study. There were no significant changes in mean blood pressure, glomerular filtration rate, creatinine, albumin, and plasma aldosterone concentrations during the observation period in either group. U-Prot/U-Cr (mg/mg Cr) was reduced from 2.43 ± 4.85 at baseline to 1.66 ± 3.51 at sixth month (p = 0.003) in group 1. In addition, U-TGF-β1/U-Cr (ng/mg Cr) was also reduced from 22.50 ± 6.65 at baseline to 17.78 ± 10.94 at sixth month (p = 0.041) in the same group. U-TGF-β1/U-Cr and U-Prot/U-Cr ratios after the sixth month were not found significant compared with baseline values in group 2. Conclusion. Spironolactone reduced both proteinuria and urinary TGF-β1 excretion in CKD patients. We consider that spironolactone would be beneficial to prevent progression of renal fibrosis in CKD.