BACKGROUND: The recent growing evidence that the proximal tubule underlies the
early pathogenesis of diabetic kidney disease (DKD) is unveiling novel and
promising perspectives. This pathophysiological concept links tubulointerstitial
oxidative stress, inflammation, hypoxia, and fibrosis with the progression of
DKD. In this new angle for DKD, the prevailing molecular mechanisms on proximal
tubular cells emerge as an innovative opportunity for prevention and management
of DKD as well as to improve diabetic dysmetabolism.
SUMMARY: The mercapturate pathway (MAP) is a classical metabolic detoxification
route for xenobiotics that is emerging as an integrative circuitry detrimental to
resolve tubular inflammation caused by endogenous electrophilic species. Herein
we review why and how it might underlie DKD. Key Messages: MAP is a hallmark of
proximal tubular cell function, and cysteine-S-conjugates might represent targets
for early intervention in DKD. Moreover, the biomonitoring of urinary
mercapturates from metabolic inflammation products might be relevant for the
implementation of preventive/management strategies in DKD.info:eu-repo/semantics/publishedVersio
