Table 2.

Factors and mechanisms relevant for endogenous Nrf2 repression in human CKD.

Factor	Possible Mechanism	Observed Effects in Patients with CKD	Reference for the Patient Data
Increased GSK-3β	GSK-3β → phosphorylation of Nrf2 → ubiquitinylation by β-TrCP → Nrf2 degradation ↑	ADPKD_CKD1–3b: kidney tissue, Nrf2 protein ↓	[144] *
Uremic toxins Indoxyl sulfate	↓ Nrf2 gene and protein expression with high indoxyl-sulfate concentrations	CKD-5HD: PBMCs, plasma indoxyl sulfate (mean ~29 mg/L) correlated negatively with Nrf2 gene expression	[156]

* The increase in GSK-3β was only shown in the ADPKD mouse model in this publication. Abbreviations: GSK-3β—glycogen synthase kinase 3; Nrf2—Nuclear factor erythroid 2-related factor 2; β-TrCP—F-box/WD repeat-containing protein 1A; ADPKD—Autosomal dominant polycystic kidney disease; CKD—chronic kidney disease; HD—hemodialysis, PBMC—peripheral blood mononuclear cell; →—leading to, ↑—increased; ↓—decreased.