Antifibrotic effects of aldosterone receptor blocker (spironolactone) in patients with chronic kidney disease.
OBJECTIVE
Proteinuria and transforming growth factor beta (TGF-beta) are parameters that can lead to glomerulosclerosis and tubulointerstitial fibrosis. All components of the renin-angiotensin-aldosterone system (RAAS) activate the TGF-beta. 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-beta1 (U- TGF-beta1) 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-beta1/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-beta1/U-Cr and U-Prot/U-Cr ratios after the sixth month were not found significant compared with baseline values in group 2.


CONCLUSIONS
Spironolactone reduced both proteinuria and urinary TGF-beta1 excretion in CKD patients. We consider that spironolactone would be beneficial to prevent progression of renal fibrosis in CKD.
Guney
Ibrahim
I
Konya Research and Training Hospital, Nephrology Department, Konya, Turkey. driguney71@yahoo.com
Selcuk
N Yilmaz
NY
Altintepe
Lutfullah
L
Atalay
Huseyin
H
Başarali
M Kemal
MK
Büyükbaş
Sadik
S
D018674:Adrenergic Antagonists / Q000627:therapeutic use; D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D018450:Disease Progression; D005260:Female; D005355:Fibrosis / Q000188:drug therapy; D006801:Humans; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000652:urine; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D011446:Prospective Studies; D013148:Spironolactone / Q000627:therapeutic use*; D053773:Transforming Growth Factor beta1 / Q000652:urine
D018674:Adrenergic Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D053773:Transforming Growth Factor beta1; D013148:Spironolactone