Oxidative stress contributes to the progression of chronic kidney disease (CKD) and CKD-related mortality. The nuclear factor erythroid 2-related factor 2 (Nrf2) is essential in the regulation of cellular redox status, and Nrf2-activating therapies are under evaluation in several chronic diseases, including CKD. It is therefore inevitable to understand how Nrf2 behaves in advancing CKD. We analyzed Nrf2 protein concentrations in patients with varying extents of CKD but without renal replacement therapy, and in healthy subjects. Compared to healthy controls, Nrf2 protein was upregulated in mild to moderate kidney function impairment (G1–3). Within the CKD population, we found a significant positive correlation between Nrf2 protein concentration and kidney function (estimated glomerular filtration rate). In severe kidney function impairment (G4,5), Nrf2 protein was reduced compared to mild to moderate kidney function impairment. We conclude that Nrf2 protein concentration in severe kidney function impairment is reduced relative to the mild to moderate kidney function impairment where increased Nrf2 protein concentrations prevail. With respect to the implementation of Nrf2 targeted therapies, it will be necessary to explore in which population of patients with CKD such therapies are able to effectively add to the endogenous Nrf2 activity.

Peripheral blood mononuclear cells contain secretory granules with Perforin and Granzyme B for defense against pathogens. The objective of the present study was to compare the effects of immunosuppressive induction therapies on Perforin and Granzyme B transcripts in kidney transplant recipients. Transcripts were determined in 408 incident kidney transplant recipients eight days posttransplant using quantitative real-time PCR. Compared to 90 healthy subjects, the median Perforin transcripts were lower in kidney transplant recipients with blood-group ABO-incompatible donors (N = 52), compatible living donors (N = 130), and deceased donors (N = 226) (25.7%; IQR, 6.5% to 46.0%; 31.5%; IQR, 10.9% to 57.7%; and 35.6%; IQR, 20.6% to 60.2%; respectively; p = 0.015 by the Kruskal–Wallis test). Kidney transplant recipients who were treated with thymoglobulin (N = 64) had significantly lower Perforin as well as Granzyme B compared to all other induction therapies (N = 344) (each p < 0.001). Receiver operator characteristics analysis showed that both Perforin (area under curve, 0.919) and Granzyme B (area under curve, 0.915) indicated thyroglobulin-containing induction therapies. Regression analysis showed that both reduction in plasma creatinine and human leukocyte antigen mismatches were positively associated with elevated Perforin/Granzyme B transcript ratio posttransplant. We conclude clinical parameters and therapies affect Perforin and Granzyme B transcripts posttransplant.