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

Güney, İ̇brahim; Selçuk, Nedim Yılmaz; Altıntepe, Lütfullah; Atalay, Hüseyin; Başaralı, Mustafa Kemal; Büyükbaş, Sadık

doi:10.3109/08860220903150312

Cited by 46 publications

(29 citation statements)

References 27 publications

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“…In the patients who received these agents, the serum level of aldosterone decreased significantly because of a substantial decline in the amount or effect of angiotensin 2 on its receptors, so the effect of spironolactone on decreasing proteinuria might be due to other mechanisms such as an antifibrotic effect. 33 In our study serum K + increased significantly 34 a similar result was obtained. Some thiazide diuretic side effects are hyperlipidemia, hyperuricemia, hypokalemia, and hyperglycemia.…”

Section: Discussionsupporting

confidence: 88%

Evaluation of spironolactone plus hydrochlorothiazide in reducing proteinuria in type 2 diabetic nephropathy

Momeni

Behradmanesh

Kheiri

et al. 2013

J Renin Angiotensin Aldosterone Syst

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Introduction: Inhibitors of the renin-angiotensin aldosterone system (RAAS) are the basic drugs for treatment of diabetic nephropathy, as to some extent is spironolactone. The aim of the study was to evaluate the effect of spironolactone versus spironolactone plus hydrochlorothiazide in decreasing proteinuria in type 2 diabetic mellitus (T2DM) patients. Methods: In a double-blind clinical trial, 60 T2DM patients with nephropathy randomly assigned to three equal groups were enrolled. Spironolactone (50 mg/day) plus placebo, spironolactone (50 mg/day) plus hydrochlorothiazide (25 mg/day), and hydrochlorothiazide (25 mg/day) plus placebo were prescribed, respectively. The duration of treatment was three months for all patients. Urine protein was measured at the beginning and end of the study and analysis of data was performed. Results: Twenty-six of the patients were male, with a total mean age of 56.8±8.3 years. Mean 24-h urine protein was reduced in patients in groups 1 and 2 compared to the third group (p < 0.001). Serum potassium in the first group showed a significant increase of 0.26 meq/lit with mean 4.64 ± 0.28 meq/lit (p=0.002), but it did not change in the second and third groups. Conclusion: Our results showed that spironolactone plus hydrochlorothiazide is an effective and inexpensive modality in the treatment of diabetic nephropathy without increasing serum potassium.

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Section: Discussionsupporting

confidence: 88%

Evaluation of spironolactone plus hydrochlorothiazide in reducing proteinuria in type 2 diabetic nephropathy

Momeni

Behradmanesh

Kheiri

et al. 2013

J Renin Angiotensin Aldosterone Syst

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show abstract

“…So far, most of these studies have involved the addition of spironolactone to RAS blockade with an ACEi or ARB. In diabetic nephropathy patients, spironolactone provides additional suppression of albuminuria compared to RAS blockade alone, and this protection appears to be partly independent of any effect on blood pressure (Guney et al, 2009; Mehdi et al, 2009; Esteghamati et al, 2013). Similar findings have been found in patients with albuminuria resulting from non-diabetic CKD (Furumatsu et al, 2008; Tylicki et al, 2008; Bianchi et al, 2010).…”

Section: Mr Signaling In Kidney Fibrosismentioning

confidence: 99%

“…Similar findings have been found in patients with albuminuria resulting from non-diabetic CKD (Furumatsu et al, 2008; Tylicki et al, 2008; Bianchi et al, 2010). Further analysis has shown that the protective effects of spironolactone are associated with reductions in the urine levels of transforming growth factor β TGF-β1 (Guney et al, 2009), collagen IV (Furumatsu et al, 2008), and amino-terminal propeptide of type III procollagen (Tylicki et al, 2008), suggesting that spironolactone is inhibiting renal fibrosis in these patients.…”

Section: Mr Signaling In Kidney Fibrosismentioning

confidence: 99%

Mineralocorticoid Receptor Signaling as a Therapeutic Target for Renal and Cardiac Fibrosis

Tesch

Young

2017

Front. Pharmacol.

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Activation of the mineralocorticoid receptor (MR) plays important roles in both physiological and pathological events. Blockade of MR signaling with MR antagonists (MRAs) has been used clinically to treat kidney and cardiac disease associated with hypertension and other chronic diseases, resulting in suppression of fibrosis in these organs. However, the current use of steroidal MRAs has been limited by off target effects on other hormone receptors or adverse effects on kidney tubular function. In this review, we summarize recent insights into the profibrotic roles of MR signaling in kidney and cardiovascular disease. We review experimental in vitro data identifying the pathological mechanisms associated with MR signaling in cell types found in the kidney (mesangial cells, podocytes, tubular cells, macrophages, interstitial fibroblasts) and heart (cardiomyocytes, endothelial cells, vascular smooth muscle cells, macrophages). In addition, we demonstrate the in vivo importance of MR signaling in specific kidney and cardiac cell types by reporting the outcomes of cell type selective MR gene deletion in animal models of kidney and cardiac disease and comparing these findings to those obtained with MRAs treatment. This review also includes a discussion of the potential benefits of novel non-steroidal MRAs for targeting kidney and cardiac fibrosis compared to existing steroidal MRAs, as well as the possibility of novel combination therapies and cell selective delivery of MRAs.

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“…Therefore, CTRP1 may represent a molecular link between obesityrelated hypertension, ORG and Ald blockers. CTRP1 may be renoprotective in patients with activated MR signaling in target tissue and chronic kidney disease (42). In the transgenic Ren2 rat, podocyte foot process effacement is normalized by treatment with spironolactone and is accompanied by a reduction in albuminuria as well as attenuated NADPH oxidase activity (43).…”

Section: Aldosteronementioning

confidence: 99%

Obesity-related glomerulopathy and podocyte injury a mini review

Carpi¹

2012

Front Biosci

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Obesity-related glomerulopathy (ORG) is morphologically defined as focal segmental glomerulosclerosis and glomerulomegaly. Podocyte hypertrophy and reduced density are related to proteinuria which in a portion of patients is in the nephrotic range and evolvs towards renal failure. This article reviews the pathogenetic mechanisms of podocyte injury or dysfunction and lists new possible antiproteinuric strategies based on pharmaceutical targeting of the reported pathogenetic mechanisms. The pathogenetic mechnisms discussed include: renin angiotensin system, plasminogen activation inhibitor-1 (PAI-1), lipid metabolism, adiponectin, macrophages and proinflammatory cytokines, oxidative stress. The proposed antiproteinuric strategies include: AT2 receptor blockers; adipokine complement C19 TNF-related protein-1 blocker; selective PAI-1 inhibitor; farnesoid x receptor activation; increase of circulating adiponectin; selective antiinflammatory drugs; more potent antioxidants (Heme oxigenase, NOX4 inhibitors). However, because ORG is a rare disease, the need for a long term pharmaceutical approach in obese proteinuric patients should be carefully evaluated and limited to the cases with progressive loss of renal function.

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

Abstract: 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.

Cited by 46 publications

References 27 publications

Evaluation of spironolactone plus hydrochlorothiazide in reducing proteinuria in type 2 diabetic nephropathy

Evaluation of spironolactone plus hydrochlorothiazide in reducing proteinuria in type 2 diabetic nephropathy

Mineralocorticoid Receptor Signaling as a Therapeutic Target for Renal and Cardiac Fibrosis

Obesity-related glomerulopathy and podocyte injury a mini review

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