With the demonstrated cardiovascular- and kidney-protective benefits of medications such as sodium/glucose cotransporter 2 inhibitors, renin-angiotensin-aldosterone system inhibitors, and mineralocorticoid receptor antagonists, there are increased rates of initiation and use of combinations of these agents. The same mechanisms that allow for the reduction of glomerular hypertension and blood pressure limit the ability to maintain kidney perfusion in the setting of volume depletion and relative hypotension and, as a result, increase the risk of development of acute kidney injury (AKI) and the severity of AKI.