Abstract
There is a growing body of experimental and clinical evidence supporting mineralocorticoid receptor (MR) activation as a powerful mediator of renal damage in laboratory animals and humans. Multiple pathophysiological mechanisms are proposed, with the strongest evidence supporting aldosterone‐induced vasculopathy, exacerbation of oxidative stress and inflammation, and increased growth factor signalling promoting fibroblast proliferation and deranged extracellular matrix homeostasis. Further involvement of the MR is supported by extensive animal model experiments where MR antagonists (such as spironolactone and eplerenone) abrogate renal injury, including ischaemia‐induced damage. Additionally, clinical trials have shown MR antagonists to be beneficial in human chronic kidney disease (CKD) in terms of reducing proteinuria and cardiovascular events, though current studies have not evaluated primary end points which allow conclusions to made about whether MR antagonists reduce mortality or slow CKD progression. Although differences between human and feline CKD exist, feline CKD shares many characteristics with human disease including tubulointerstitial fibrosis. This review evaluates the evidence for the role of the MR in renal injury and summarizes the literature concerning aldosterone in feline CKD. MR antagonists may represent a promising therapeutic strategy in feline CKD.
Highlights
Beyond its physiological role in renal sodium reabsorption and potassium excretion, there is extensive experimental evidence implicating excessive aldosterone activation of mineralocorticoid receptors (MR) in nonclassical sites, including the endothelium, vascular smooth muscle cells (VSMCs), cardiomyocytes, inflammatory cells, renal podocytes and fibroblasts, in causing tissue injury
Given the expanding evidence base from in vitro and in vivo experimental studies and from human medicine, it seems likely that aldosterone and MR activation is an important player in the pathogenesis of feline chronic kidney disease (CKD)
That experimental models may not be directly translatable to the clinical situation and that differences in CKD pathogenesis exist between humans and cats
Summary
Beyond its physiological role in renal sodium reabsorption and potassium excretion, there is extensive experimental evidence implicating excessive aldosterone activation of mineralocorticoid receptors (MR) in nonclassical sites, including the endothelium, vascular smooth muscle cells (VSMCs), cardiomyocytes, inflammatory cells, renal podocytes and fibroblasts, in causing tissue injury. Increased plasma aldosterone levels are a risk factor for kidney injury in human clinical studies, and MRA treatment has been shown to be beneficial in numerous rodent models of renal disease and in human patients, for example by abrogating renal histopathological changes and reducing proteinuria and blood pressure.
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