Bridging the gap-Rethinking the role of the adrenal gland in chronic kidney disease from the feline perspective

Chronic kidney disease (CKD) is the most common metabolic disease in domestic cats. Unlike humans and dogs, CKD in cats seems to have a highly complex and multifactorial etiology. Despite great effort being poured into research trying to elucidate possible pathways for the pathogenesis of CKD, there is still a lack of understanding regarding its initiating and progression factors. There is also a lack of therapeutic options for these patients, with most treatment plans relying on a low-phosphate diet, dietary protein modification and medical management of complications (e.g. hypertension) as they arise. In this review, we propose the hypothalamic-pituitary-adrenal (HPA) axis plays a central role in the development, pathophysiology and progression of feline chronic kidney disease. The adrenal glands and the hormones they secrete, in particular, may act as lynchpins in chronic kidney disease, mediating virtually every aspect of the disease: from the establishment of fibrosis and kidney damage to the development of hypertension and a pro-inflammatory status. By compiling the available research regarding the influence of adrenal hormones and the HPA axis, we hope to highlight possible future areas of scientific interest regarding feline CKD as well as possible aspects in which the cat may act as a model for research in human medicine.