Sulforaphane reprograms the metabolomic landscape of chronic kidney disease: insights from NMR-based metabolomics

Abstract

Chronic kidney disease (CKD) is characterized by systemic metabolic disturbances and oxidative stress. Nutritional interventions using bioactive compounds such as sulforaphane (SFN) may represent a promising adjuvant strategy to attenuate these alterations. This study evaluated the effects of SFN supplementation on the untargeted metabolomic profile of non-dialysis CKD patients. A randomized, placebo-controlled clinical trial was conducted in 14 patients with CKD stages 3–5 who received either 400 µg per day of SFN or placebo for 30 days. Serum samples were analyzed using proton nuclear magnetic resonance (¹H NMR) spectroscopy to identify metabolomic alterations and their correlations with markers of oxidative stress, inflammation, and gene expression. SFN supplementation tended to reduce 2-hydroxyisovalerate and glycerol levels, metabolites associated with insulin resistance and oxidative stress, and attenuated methanol elevation. Correlations were identified between heme oxygenase-1 (HO-1) and several amino acids, and between NRF2 and glycerol, suggesting an interplay between amino acid metabolism and antioxidant defense. Overall, SFN modulated the metabolomic profile of CKD patients, particularly metabolites related to mitochondrial function, lipid metabolism, and oxidative balance. These findings demonstrate that NMR-based metabolomics is a powerful non-invasive approach for elucidating the molecular effects of nutritional therapies in CKD and support SFN as a potential nutraceutical strategy in renal care.