Key enzyme in charge of ketone reabsorption of renal tubular SMCT1 may be a new target in diabetic kidney disease.

This article investigates the role of sodium-coupled monocarboxylate transporter 1 (SMCT1), a key transporter responsible for ketone body reabsorption, in diabetic kidney disease (DKD). The study found that SMCT1 expression and renal β-hydroxybutyrate (β-HB) levels are decreased in DKD patients and diabetic mice, contributing to impaired renal tubular function and metabolic reprogramming from lipolysis to glycolysis. Using diabetic and renal tubule–specific Slc5a8 (the gene encoding SMCT1) knockout mouse models, the research demonstrated that SMCT1 deficiency leads to renal structural damage, mitochondrial dysfunction, and energy metabolism disorders, which were partially alleviated by supplementation with the ketone precursor 1,3-butanediol. These findings suggest that decreased SMCT1-mediated ketone reabsorption plays a significant role in DKD pathogenesis and that SMCT1 may represent a promising therapeutic target for treating DKD.