Aldosterone and the mineralocorticoid receptor in renal injury: A potential therapeutic target in feline chronic kidney disease

Spencer, S and Wheeler-Jones, C P D and Elliott, J (2020) Aldosterone and the mineralocorticoid receptor in renal injury: A potential therapeutic target in feline chronic kidney disease. JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS.

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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.

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