Table 1.

Key points of the most relevant NRF2 activators and future view of their use in CKD.

NRF2 Activators and Ref.	Strengths	Weaknesses	Future Perspectives
Bardoxolone methyl [69,73,77,78,80,82]	GFR ↑	Albuminuria ↑	Its strengths could be present without its weaknesses in subjects who: - have not previously been hospitalized for heart failure and with BNP levels less than 200 pg/mL -other etiologies of CKD (ADPKD, Alport syndrome)
	Delayed progression to ESRD	Morality↑ and serious side effects in some groups
Curcumin [84,94,98]	Serum creatinine levels ↓	No significant impact on proteinuria, blood urea nitrogen	Curcumin derivatives could be a better option from a pharmacokinetic point of view while maintaining the beneficial effects of the original compound
	Fasting blood glucose ↓	Unstable molecular structure
	Systolic blood pressure ↓	High dosages to obtain the known effects
	Total cholesterol ↓	Absorption ↓
		Degradation and elimination ↑
Sulforaphane [65,105,106,108]	Good bioavailability	Unstable molecular structure	A clinical trial could bring a better understanding of its future potential
		Liver first-pass effect↑
		Water solubility ↓
Cinnamic aldehyde [130,131,132,133]	Improves DM symptoms	Bioavailability?	There is less data available on its effect on DKD, which highlights the direction future studies need to take.
		Possible side effects
Resveratrol [137,139]	It can target at once several pathophysiological mechanisms	Bioavailability ↓	There are some conflicting results, which need to be evaluated in further studies
	Possible no significant side effects?	Metabolism ↑
		water solubility ↓

raised ↑; lower ↓; B-type natriuretic peptide (BNP); autosomal dominant polycystic kidney disease (ADPKD); Diabetes mellitus (DM); Glomerular filtration rate (GFR); End-stage renal disease (ESRD); Chronic kidney disease (CKD); Diabetic kidney disease (DKD).