Indoxyl Sulfate and p-Cresyl Sulfate in Chronic Kidney Disease. Could These Toxins Modulate the Antioxidant Nrf2-Keap1 Pathway?

Protein-bound uremic toxins (i.e., indoxyl sulfate or p-cresyl sulfate), produced by intestinal bacteria, are accumulated in the plasma of chronic kidney disease (CKD) patients. These toxins interact negatively with biological functions, having potent oxidative stress-inducing effects and a pathological effect on cardiovascular disease. Recent research in CKD has shown that oxidative stress and inflammation can be compounded by impaired activation of the nuclear factor (erythroid-2-related factor)-2 (Nrf2)-Kelch-like ECH associating protein-1 (Keap1) pathway, a major cellular defense mechanism. However, to date, many questions arise regarding the role of this system in CKD. For example, protein-bound uremic toxins promote oxidative stress in CKD patients, but their putative effect on the Nrf2-Keap1 system has yet to be examined in these patients. This review will focus on the putative relationship among protein-bound uremic toxins, oxidative stress, and a possible decreased expression of Nrf2 in CKD.