The role of aldosterone blockade in murine lupus nephritis

Monrad, Seetha U.; Killen, Paul D.; Anderson, Marie A.; Bradke, Amanda; Kaplan, Mariana J.

doi:10.1186/ar2353

Cited by 36 publications

(21 citation statements)

References 54 publications

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“…Similar results with spironolactone or eplerenone were obtained in type 2 diabetic rats (17), mice (18), and obese spontaneously hypertensive rats (SHR) (19). Furthermore, spironolactone and eplerenone have been shown to attenuate the progression of proteinuria, glomerular injury, and tubulointerstitial fibrosis in murine lupus nephritis (20) or in rats treated with angiotensin II and an nitric oxide synthase inhibitor (21), cyclosporine A (22 -24), or radiation (25). Treatment with spironolactone prevents tubulointerstitial fibrosis and tubular apoptosis in mice subjected to unilateral ureteral occlusion (26) and in rats that underwent ischemia and reperfusion (27) or 5 / 6 nephrectomy (28).…”

Section: Preclinical Evidence For Renoprotective Effects Of Mr Blockerssupporting

confidence: 62%

Drug Discovery for Overcoming Chronic Kidney Disease (CKD): Pharmacological Effects of Mineralocorticoid-Receptor Blockers

et al. 2009

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Abstract. There is increasing evidence demonstrating that the renoprotective effects of mineralocorticoid receptor (MR) blockade are independent of the effects exerted by reninangiotensin inhibitors. MR is expressed not only in tubular cells but also in other renal cells including glomerular mesangial cells, podocytes, and renal interstitial fibroblasts. Animal experiments have shown that MR blockers prevent aldosterone-induced proteinuria, glomerular injury, and tubulointerstitial fibrosis. In vitro studies have also demonstrated that MR blockers inhibit aldosterone-induced renal cell damage. Recent clinical studies have shown that treatment with MR blockers attenuates the development of proteinuria in patients with chronic kidney disease (CKD) and hypertension, independent of changes in blood pressure. In some cases, MR blockers elicit potent renoprotective effects in conditions where aldosterone levels are not elevated. These data suggest that treatment with MR blockers may possibly present an effective therapeutic strategy for patients with CKD.

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Section: Preclinical Evidence For Renoprotective Effects Of Mr Blockerssupporting

confidence: 62%

Drug Discovery for Overcoming Chronic Kidney Disease (CKD): Pharmacological Effects of Mineralocorticoid-Receptor Blockers

et al. 2009

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“…The ACE inhibitor-induced improvement in renal disease was correlated with reduced transforming growth factor-b expression in the kidneys. In a recent experiment on the effect of aldosterone blockade on the development and progression of glomerulonephritis in a murine model of SLE, spironolactone significantly reduced nephrotic-range proteinuria, and the spironolactone group showed less severe glomerular injury than the control group [15]. The study demonstrated significantly lower serum levels of anti-ssDNA and anti-dsDNA antibodies in the spironolactone group than in the control group by 36 weeks of age, thereby highlighting the potent anti-inflammatory, immune-mediating component of RAAS blockade.…”

Section: Class I and Class Ii (Isn/rps) Lupus Nephritismentioning

confidence: 97%

Recent advances in the treatment of lupus nephritis

Uchida

Nitta

2011

Clin Exp Nephrol

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Lupus nephritis is a common complication of systemic lupus erythematosus (SLE) which is associated with significant morbidity and mortality. The concept of two phases of therapy for lupus nephritis, such as an induction phase and a maintenance phase, is widely accepted. Since the renal involvement in SLE is heterogeneous, the treatment of lupus nephritis is governed by its pathological type and ranges from nonspecific measures, such as maintenance of adequate blood pressure control and blockade of the renin-angiotensin-aldosterone system, to the use of immunosuppressive agents. Cyclophosphamide (CYC) in combination with prednisone has been the standard method of treatment of the proliferative forms of lupus nephritis. However, the high rates of progression to end-stage renal disease coupled with the adverse effects of CYC and prednisone have led to an intensive search for more effective and less toxic therapies for lupus nephritis. We review the options available for the treatment of proliferative and membranous lupus nephritis and summarize the results of recently published clinical trials that add new perspectives to the management of kidney disease in SLE.

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“…In a recent experiment on the effect of aldosterone blockade on the development and progression of glomerulonephritis in a murine model of lupus, spironolactone significantly reduces the incidence of nephrotic range proteinuria and, on histology, showed far less severe glomerular injury (no crescents, diminished overall cellularity, and less prominent deposits in the capillary loops and mesangium) compared with controls. 16 The investigators found significant differences in levels of anti-ssDNA and anti-dsDNA antibodies between control mice and mice treated with spironolactone by 36 ISN class III, focal lupus nephritis, is defined as focal segmental and/or global endocapillary and/or extracapillary glomerulonephritis affecting Ͻ50% of the sampled glomeruli. ISN class IV, diffuse lupus nephritis, has diffuse segmental and/or global endocapillary and/or extracapillary glomerulonephritis affecting Ն50% of glomeruli.…”

Section: Conservative Nonimmunomodulatory Therapy Is Appropriate Formentioning

confidence: 99%

Updates on the Treatment of Lupus Nephritis

Bomback

Appel

2010

Journal of the American Society of Nephrology

158

139

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The role of aldosterone blockade in murine lupus nephritis

Abstract: Background The purpose of this study was to examine the effect of aldosterone receptor blockade on the immunopathogenesis and progression of nephritis in the (NZB × NZW) F 1 murine lupus model.

Cited by 36 publications

References 54 publications

Drug Discovery for Overcoming Chronic Kidney Disease (CKD): Pharmacological Effects of Mineralocorticoid-Receptor Blockers

Drug Discovery for Overcoming Chronic Kidney Disease (CKD): Pharmacological Effects of Mineralocorticoid-Receptor Blockers

Recent advances in the treatment of lupus nephritis

Updates on the Treatment of Lupus Nephritis

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