Hypoxia and chronic kidney disease: Possible mechanisms, therapeutic targets, and relevance to cats

Abstract

There is mounting evidence that kidney ischaemia/hypoxia plays an important role in feline chronic kidney disease (CKD) development and progression, as well as in human disease and laboratory animal models. Ischaemic acute kidney injury is widely accepted as a cause of CKD in people and data from laboratory species has identified some of the pathways underlying this continuum. Experimental kidney ischaemia in cats results in morphological changes, namely chronic tubulointerstitial inflammation, tubulointerstitial fibrosis, and tubular atrophy, akin to those observed in naturally-occurring CKD. Multiple situations are envisaged that could result in acute or chronic episodes of kidney hypoxia in cats, while risk factors identified in epidemiological studies provide further support that kidney hypoxia contributes to spontaneously occurring feline CKD. This review evaluates the evidence for the role of kidney ischaemia/hypoxia in feline CKD and the proposed mechanisms and consequences of kidney hypoxia. As no effective treatments exist that substantially slow or prevent feline CKD progression, there is a need for novel therapeutic strategies. Targeting kidney hypoxia is one such promising approach, with therapies including those that attenuate the hypoxia-inducible factor (HIF) pathway already being utilised in human CKD.