Renal Ischemia-Reperfusion and Uremic Toxins Modulate the Aortic Adenosinergic Axis in Acute Kidney Injury

Acute kidney injury (AKI) is characterized by a rapid decline or sudden loss of renal function over hours to days. Pathophysiological triggers such as renal ischemia-reperfusion (IR) injury and the accumulation of uremic toxins (UTs), notably indoxyl sulfate (IS), can initiate AKI and affect vascular beds distant from the ischemic site, like the aorta. In this context, purinergic signaling becomes relevant, since its components regulate vascular tone and inflammatory responses. This study aimed to evaluate the impact of AKI induced by IR with or without IS administration on purinergic signaling in the aorta of mice. Renal ischemia was induced by the occlusion of the left renal pedicle for 60 min, followed by reperfusion for 8 days (IR 8) or 15 days (IR 15). Some animals were also treated with saline solution or IS for 15 days. The IR15 group exhibited increased plasma IS concentrations and upregulated adenosine receptor gene expression. Furthermore, in the IR+IS group, there was increased expression of A1, A2a, NTPDase 1, and 2. This shift toward an adenosine-enriched signaling environment may represent a key mechanism linking renal injury to systemic vascular inflammation.