Chronic kidney disease is associated with attenuated plasma metabolome response to oral glucose tolerance testing

Chronic kidney disease (CKD), a major public health problem, is associated with decreased anabolic response to insulin contributing to protein-energy wasting. Targeted metabolic profiling of the response to oral glucose tolerance testing (OGTT) may help identify metabolic pathways contributing to disruptions to insulin response in CKD. Using targeted metabolic profiling, we examined plasma metabolome in 41 moderate-to-severe non-diabetic CKD patients with estimated glomerular filtration rate (eGFR)<60ml/min per 1.73m2 (38.9+-12.7) and 20 healthy controls with normal eGFR (87.2+-17.7) before and after 2h of 75g oral glucose load. Compared to controls, CKD participants had higher lactate: pyruvate (L:P) ratio both at fasting and after oral glucose challenge. Total energy production estimated through GTP:GDP ratio was impaired during OGTT despite similar fasting GTP:GDP ratio. CKD group had sustained elevation of vitamin B family members, TCA cycle metabolites, and purine nucleotides in response to glucose challenge. Metabolic profiling in response to OGTT suggests a broad disruption of mitochondrial energy metabolism in CKD patients. These findings motivate further investigation into insulin sensitizers in patients with non-diabetic CKD and their impact on energy metabolism.