Abstract
Acute kidney injury (AKI) refers to an abrupt decrease in kidney function. It affects approximately 7% of all hospitalized patients and almost 35% of intensive care patients. Mortality from acute kidney injury remains high, particularly in critically ill patients, where it can be more than 50%. The primary causes of AKI include ischemia/reperfusion (I/R), sepsis, or nephrotoxicity; however, AKI patients may present with a complicated etiology where many of the aforementioned conditions co-exist. Multiple bio-markers associated with renal damage, as well as metabolic and signal transduction pathways that are involved in the mediation of renal dysfunction have been identified as a result of the examination of models, patient samples, and clinical data of AKI of disparate etiologies. These discoveries have enhanced our ability to diagnose AKIs and to begin to elucidate the mechanisms involved in their pathogenesis. Studies in our laboratory revealed that the expression and activity of spermine/spermidine N1-acetyltransferase (SAT1), the rate-limiting enzyme in polyamine back conversion, were enhanced in kidneys of rats after I/R injury. Additional studies revealed that the expression of spermine oxidase (SMOX), another critical enzyme in polyamine catabolism, is also elevated in the kidney and other organs subjected to I/R, septic, toxic, and traumatic injuries. The maladaptive role of polyamine catabolism in the mediation of AKI and other injuries has been clearly demonstrated. This review will examine the biochemical and mechanistic basis of tissue damage brought about by enhanced polyamine degradation and discuss the potential of therapeutic interventions that target polyamine catabolic enzymes or their byproducts for the treatment of AKI.
Highlights
Acute kidney injuries (AKI) are marked by an abrupt decrease in kidney function that may be caused by damage to the renal parenchyma or abrupt reduction in renal perfusion [1,2,3]
Studies have shown that polyamine catabolism, via alteration of polyamine levels and the production of toxic metabolites, contributes to the pathogenesis of a variety of injuries, including those of AKI of different etiologies
The enhanced catabolism of polyamines in cells can result in DNA damage, mitochondrial dysfunction, and endoplasmic reticulum stress/unfolded protein response (ERS/UPR), all of which can lead to the onset of tubular epithelial cell damage and death
Summary
Acute kidney injuries (AKI) are marked by an abrupt decrease in kidney function that may be caused by damage to the renal parenchyma or abrupt reduction in renal perfusion [1,2,3]. Examination of AKI of differing etiologies have identified multiple bio-markers that enhance our diagnostic abilities, and many molecules and pathways that further our understanding of its pathogenesis. Despite these advances, the main option for the treatment of AKI remains the provision of supportive care and renal replacement therapy.
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