Gut-Derived Uremic Toxins as a Risk Factor for Vascular Damage in Patients with Chronic Kidney Disease

Patients with chronic kidney disease (CKD) have a markedly increased cardiovascular risk that is not fully explained by traditional risk factors. Gut-derived uremic toxins, indoxyl sulfate (IS), indole-3-acetic acid (IAA), and p-cresyl sulfate (pCS), are poorly cleared by dialysis and may contribute to vascular damage. This cross-sectional observational study included 70 patients with CKD under different clinical conditions (pre-dialysis, peritoneal dialysis, hemodialysis, and kidney transplantation) and 17 healthy controls. Serum levels of IS, IAA, pCS and Klotho were measured, and vascular damage was assessed by carotid intima-media thickness (IMT) using ultrasound. CKD patients showed higher concentrations of IS, IAA, and pCS compared with controls, with the highest levels observed in hemodialysis patients. Peritoneal dialysis was associated with elevated IS and pCS, whereas in kidney transplantation, IS and IAA levels did not differ significantly from controls, and pCS remained elevated. Carotid IMT was higher in patients with diabetes and those undergoing hemodialysis. IAA correlated significantly with left/mean IMT, and mean IMT was the only parameter associated with previous cardiovascular events. These findings suggest that gut-derived uremic toxins, particularly IAA, might be associated with subclinical vascular damage in advanced CKD, although larger studies are needed to confirm these associations.