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

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.

Esaxerenone inhibits the macrophage-to-myofibroblast transition through mineralocorticoid receptor/TGF-β1 pathway in mice induced with aldosterone

“…CKD, however, can be considered a state of relative aldosteronism. In human clinical studies, elevated plasma ALD levels are a risk factor for kidney injury ( 17 ). In our study, we continuously infused ALD to mimic the clinical condition of CKD patients with renal injury, and we observed changes in renal pathology, deterioration of renal function, and an increase in blood pressure in model mice.…”

Hyperaldosteronemia as a risk factor of renal dysfunction in patients with heart failure with preserved ejection fraction

“…Независимое от давления влияние альдостерона было выявлено в клинических исследованиях [24] и различных экспериментальных моделях повреждения почек, таких как диабетическая нефропатия [25], гломерулонефрит [26], ишемия/реперфузия [27] и др. [28]. В нашем исследовании связь между альдостероном и почечной дисфункцией также сохранялась после учета влияния АГ и СД -двух важнейших факторов риска ХБП [29,30].…”

Consenso de la Sociedad Latinoamericana de Nefrología e Hipertensión en relación con el papel de los antagonistas del receptor mineralocorticoide en enfermedad renal crónica

“…Más allá de su papel fisiológico en la reabsorción renal de sodio y la excreción de potasio, existe amplia evidencia experimental de activación excesiva de los RM en sitios «no clásicos», como el endotelio, las células del músculo liso vascular, los cardiomiocitos, las células inflamatorias, los podocitos y fibroblastos, que finalmente pueden participar en el proceso que lleva a lesión tisular 20 . En el diabético, estos efectos deletéreos de lesión tisular pueden observarse primordialmente en riñones, sistema cardiovascular y sistema nervioso central 21 .…”