NFE2L2 and stage 5 chronic kidney disease: NRF2 also downregulates important inflammatory cytokines in COVID-19, but the clinical trial with sulforaphane did not show any improvement in hospitalized patients with suspected or confirmed COVID-19 infection.5 Another example is for bardoxolone methyl which did not reduce the risk of end-stage renal disease or death from cardiovascular causes in a clinical trial of patients with type 2 diabetes mellitus and stage 4 chronic kidney disease.6 In addition, formulation difficulties related to low solubility, poor bioavailability and stability also limit the clinical utility of NRF2 modulators.