Branched-chain ketoacid dehydrogenase kinase (BCKDK) accelerates the progression of diabetic kidney disease by regulating leucine-mediated metabolic remodelling in renal tubular cells
Authors' conclusion
In summary, we identify defective leucine degradation in renal tubules of diabetic individuals and propose leucine as a causative factor for DKD, highlighting its potential as a therapeutic target for further investigation.
Study context
- Population
- Human kidney biopsies, mouse models of diabetes and cultured kidney tubular epithelial cells; individuals with diabetes for urinary leucine association
- Outcome
- Leucine metabolism in kidney tubules during DKD progression
Methodological detailshuman kidney biopsies, mouse models, cultured kidney tubular epithelial cells
- Human kidney biopsies
- Mouse models
- Cultured kidney tubular epithelial cells
Main finding
As reported in the abstract
- Defective leucine degradation and increased BCKDK expression in kidney tubules during diabetic kidney disease (DKD) progression
- Enhancing leucine degradation (BCKDK ablation or inhibition) relieved glucose-induced metabolic remodelling in tubular cells and mitigated DKD in mouse models
- Leucine accumulation stimulated metabolic remodelling via mTOR signalling; relieved by blocking leucine uptake or enhancing its degradation
- Restricting dietary leucine significantly decreased albuminuria, kidney hypertrophy and lipid accumulation in diabetic mice
- Rapid decline in kidney function correlated with higher urinary leucine-to-creatinine ratio in female and male individuals with diabetes
Original publication
BCKDK accelerates the progression of diabetic kidney disease by regulating leucine-mediated metabolic remodelling in renal tubular cells. Diabetologia. Published 16 August 2025. doi:10.
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