Involvement of Indoxyl Sulfate in Vascular Endothelial Dysfunction associated with Ischemic Acute Kidney Injury

In our previous study, we found that impaired renal function due to ischemic acute kidney injury (IAKI) recovered over time; however, the endothelial function of the thoracic aorta deteriorated from the time when renal function shifted toward recovery. In the present study, we investigated the influence of indoxyl sulfate (IS) on vascular endothelial dysfunction after the onset of IAKI by administering AST-120, which can remove IS. IAKI was induced by occlusion of the left renal artery and vein for 45 min, followed by reperfusion 2 weeks after contralateral nephrectomy. AST-120 (2.5 g/kg, p.o.) was administered at 3, 6, and 24 hours after reperfusion. At 1 and 7 days after reperfusion, a significant increase in blood IS levels was observed along with worsening of renal function. On the other hand, AST-120 administration significantly suppressed the blood IS levels but had no effect on the decline in renal function after reperfusion. Furthermore, renal function and blood IS levels at 28 days after reperfusion were not significantly different among all groups. In contrast, vascular endothelial function was markedly attenuated 28 days after reperfusion in the IAKI model. In addition, administration of AST-120 did not clearly improve this impaired vascular endothelial function, suggesting that IS may not be involved in the vascular endothelial dysfunction that occurs after the onset of IAKI. Therefore, further investigation of the detailed mechanism of the vascular endothelial dysfunction that occurs after the onset of IAKI is considered necessary.