Using a targeted metabolomics platform, we identified an abnormal metabolic profile in mice (Azushima et al) and humans DN consisting of increased levels of lactate and dysregulation of TCA Cycle intermediates, tightly correlated with albuminuria. In Asian patients with type 2 diabetes mellitus (T2DM), we found for the first time that elevated urinary lactate levels predict increased risk for developing ESKD, suggesting a role in promoting progressive kidney injury in DN. Thus, we hypothesize that renal metabolic disruptions leading to enhanced generation of lactate contribute to the pathogenesis of DN, and that increased urinary lactate levels may be a novel biomarker for risk of kidney disease progression in DN.