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Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
Published on: November 15, 2013
[Antifibrotic renal role of mineralcorticoid receptor antagonists]
Alessandra Ocello1, Sandra La Rosa1, Fulvio Fiorini2
1UOS di Nefrologia e Dialisi, P.O. "Giovanni Paolo II", Sciacca (AG), Italia.
Abstract:
Cardiovascular and renal diseases are one of the main health problems in all industrialized countries. Their incidence is constantly increasing due to the aging of the population and the greater prevalence of obesity and type 2 diabetes. Clinical evidence suggests that aldosterone and the activation of mineralocorticoid receptors (MR) have a role in the pathophysiology of cardiovascular and renal diseases. Moreover, clinical studies demonstrate the benefits of mineralocorticoid receptor antagonists (MRAs) on mortality and progression of heart and kidney disease. In addition to renal effects on body fluid homeostasis, aldosterone has multiple extrarenal effects including the induction of inflammation, vascular rigidity, collagen formation and stimulation of fibrosis. Given the fundamental role of MR activation in renal and cardiac fibrosis, effective and selective blocking of the signal with MRAs can be used in the clinical practice to prevent or slow down the progression of heart and kidney diseases. The aim of the present work is to review the role of MRAs in light of the new evidence as well as its potential use as an antifibrotic in chronic kidney disease (CKD). The initial clinical results suggest that MRAs are potentially useful in treating patients with chronic kidney disease, particularly in cases of diabetic nephropathy. We don't yet have efficacy and safety data on the progression of kidney disease up to the end stage (ESRD) and filling this gap represents an important target for future trials.
Insights
Mineralocorticoid receptor antagonists (MRAs) show promise in treating cardiovascular and kidney diseases by blocking aldosterone's harmful effects. Further research is needed to confirm their efficacy in slowing chronic kidney disease progression to end-stage renal disease.
Area of Science:
- Cardiology
- Nephrology
- Endocrinology
Background:
- Cardiovascular and renal diseases are increasing globally, linked to aging, obesity, and type 2 diabetes.
- Aldosterone and mineralocorticoid receptor (MR) activation play key roles in the pathophysiology of these diseases.
- MR antagonists (MRAs) have demonstrated benefits in reducing mortality and disease progression in heart and kidney conditions.
Purpose of the Study:
- To review the current evidence on MRAs, focusing on their antifibrotic potential in chronic kidney disease (CKD).
- To evaluate the emerging role of MRAs in managing cardiovascular and renal diseases.
Main Methods:
- Literature review of clinical studies and evidence regarding MRAs.
- Analysis of aldosterone's extrarenal effects, including inflammation and fibrosis.
- Examination of MRA's role in preventing or slowing cardiac and renal fibrosis.
Main Results:
- Aldosterone contributes to inflammation, vascular rigidity, and fibrosis in the heart and kidneys.
- MRAs effectively block MR activation, offering a strategy to mitigate fibrosis.
- Initial clinical data suggest MRAs are beneficial for CKD patients, especially those with diabetic nephropathy.
Conclusions:
- MRAs represent a potential therapeutic strategy for managing cardiovascular and renal diseases.
- Their antifibrotic properties make them promising for slowing CKD progression.
- Future trials are essential to establish MRA efficacy and safety for progression to end-stage renal disease (ESRD).
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