The aberrant glycolysis in kidney proximal tubule: potential therapeutic target for DKD

The presence of glycolysis in kidney proximal tubule has been long debated. However, recent reports suggest that aberrant glycolysis is induced in pathologic conditions and may play a critical role in kidney damage. Azushima et al. provided additional evidence that the accumulation of glycolysis-derived lactate could be the clue to understanding the pathogenesis of diabetic kidney disease. The presence of glycolysis in kidney proximal tubule has been long debated. However, recent reports suggest that aberrant glycolysis is induced in pathologic conditions and may play a critical role in kidney damage. Azushima et al. provided additional evidence that the accumulation of glycolysis-derived lactate could be the clue to understanding the pathogenesis of diabetic kidney disease. Abnormal lactate metabolism is linked to albuminuria and kidney injury in diabetic nephropathyKidney InternationalVol. 104Issue 6PreviewDiabetic nephropathy (DN) is characterized by abnormal kidney energy metabolism, but its causes and contributions to DN pathogenesis are not clear. To examine this issue, we carried out targeted metabolomics profiling in a mouse model of DN that develops kidney disease resembling the human disorder. We found a distinct profile of increased lactate levels and impaired energy metabolism in kidneys of mice with DN, and treatment with an angiotensin-receptor blocker (ARB) reduced albuminuria, attenuated kidney pathology and corrected many metabolic abnormalities, restoring levels of lactate toward normal while increasing kidney ATP content. Full-Text PDF