Abstract
In chronic kidney disease (CKD), oxidative stress and inflammation contribute to disease progression and CKD-related morbidity. The nuclear factor erythroid 2-related factor 2 (Nrf2) system plays a central role in the cellular response to oxidative and inflammatory stress. In this brief report, we describe our investigation into whether alterations in the gene expression of key Nrf2 pathway components contribute to the endogenous activation of the Nrf2 system previously reported in less advanced CKD. To this end, we quantified the gene expression of Nrf2, its regulatory protein Kelch-like ECH-associated protein 1 (KEAP1), and the Nrf2 downstream target NAD(P)H:quinone oxidoreductase 1 (NQO1) in monocytes from patients in different stages of CKD. We observed significantly elevated NQO1 gene expression in CKD stage G3b compared to CKD stages G1-3a (p < 0.05), G4 (p < 0.01), and G5 (p < 0.001). In contrast, the gene expression levels of Nrf2 and KEAP1 did not differ significantly between CKD stages. These findings suggest that endogenous activation of the Nrf2 system in moderate CKD predominantly reflects functional activation, likely at the protein level, rather than changes in the gene expression of Nrf2 or KEAP1.