Expression of the Target Gene Is Enhanced in Mononuclear Cells in Human Chronic Kidney Disease.

Reduced nuclear factor erythroid 2-related factor 2 () pathway activity was reported in models of chronic kidney disease (CKD). Pharmacological activation of is supposed to improve renal function, but data concerning the activity in human CKD are lacking. We investigated the target NAD(P)H:quinone oxidoreductase 1 () as a readout parameter for activity in monocytes of CKD patients ( = 63) compared to those of healthy controls ( = 16). The gene expression was quantified using real-time PCR and the protein content by in-cell Western assays. We found a 3-4-fold increase in gene expression in CKD 1-5 ( = 29; 3.5 for /ribosomal protein L41; < 0.001). This was accompanied by a 1.1-fold increase in protein ( = 0.06). Cardiovascular disease prevalence was higher in CKD 1-5 patients with higher compared to those with lower gene expression ( = 0.02). In advanced uremia, in dialysis patients ( = 34), gene expression was less robustly upregulated than that in CKD 1-5, while protein was not upregulated. We conclude that in mononuclear cells of CKD patients, the pathway is activated by coexisting pathogenic mechanisms, but in advanced uremia, the effectiveness of this upregulation is reduced. Both processes could interfere with pharmacological activation.