Mitochondrial energy metabolism disrupted in CKD

In patients with chronic kidney disease (CKD), metabolic profiling reveals disruptions in mitochondrial energy metabolism, a new study has found.

Researchers enrolled 41 patients with moderate-to-severe nondiabetic CKD, in whom targeted metabolic profiling was performed to assess the plasma metabolome response. A parallel group of 20 healthy controls was also included. Testing was performed at fasting and 2 hours after an oral glucose load.

At baseline, mean estimated glomerular filtration rate was 38.9 mL/min/1.73 m² in CKD patients, as opposed to 87.2 mL/min/1.73 m² in controls. Intake of glucose led to a notable anabolic response in participants, characterized by a drop in metabolites such as purine nucleotides, amino acids, and tricarboxylic acid cycle intermediates.

Of note, in oral glucose tolerance testing, CKD patients demonstrated a blunted metabolome response according to significant discrepancies in change values in the levels of 13 metabolites, including inositol, kynurenate, and glucose.

In particular, biomarkers showing attenuated response were predominantly involved in mitochondrial energy metabolism and belonged to purine nucleotide or the vitamin B families. In contrast, the lactate-to-pyruvate ratio was elevated in CKD patients during glucose testing.

“Our findings suggest that the response to oral glucose challenge in CKD may be associated with disruption in both protein anabolic response to insulin and mitochondrial energy metabolism,” the researchers said. “Uraemic toxins may link inflammation with the disruption of mitochondrial energy metabolism and the attenuated anabolic response to insulin in CKD.”