Metabolomics and Gene Expression Analysis Reveal Down-regulation of the Citric Acid (TCA) Cycle.


eMediNexus    20 November 2017

The goal of a new study published in EBiomedicine was to identify metabolic pathways that are altered in adults with non diabetic stage 3 4 CKD versus healthy adults. This study combined metabolomics GCMS with kidney gene expression studies. It was observed that urinary excretion rate of 27 metabolites and plasma concentration of 33 metabolites differed considerably among CKD patients when compared to controls. While the citric acid cycle was the most significantly affected with urinary excretion of citrate cis aconitate isocitrate 2 oxoglutarate and succinate reduced by 40 68 . Whereas reduction of the citric acid cycle metabolites in urine was replicated in an independent cohort. On the other hand expression of genes regulating aconitate isocitrate 2 oxoglutarate and succinate were markedly reduced in kidney biopsies. Additionally increased urine citrate excretion and plasma 2 oxoglutarate concentrations were detected in CKD patients during treatment with a vitamin D receptor agonist in a randomized trial. Thus it was inferred that urinary excretion of citric acid cycle metabolites and renal expression of genes regulating these metabolites were reduced in non diabetic CKD. It was stated that this finding supports the emerging view of CKD as a state of mitochondrial dysfunction.

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