Untargeted plasma 1H NMR-based metabolomic profiling in different stages of chronic kidney disease

Chronic kidney disease (CKD) is a serious public health issue affecting thousands of people worldwide. CKD diagnosis is usually made by Estimated Glomerular Filtration Rate (eGFR) and albuminuria, which limit the knowledge of the mechanisms behind CKD progression. The aim of the present study was to identify changes in the metabolomic profile that occur as CKD advances. In this sense, 77 plasma samples from patients with CDK were evaluated by 1D and 2D Nuclear Magnetic Resonance Spectroscopy (NMR). The NMR data showed significant changes in the metabolomic profile of CKD patients and the control group. Principal component analysis (PCA) clustered CKD and control patients into three distinct groups, control, stage 1 (G1)-stage 4 (G4) and stage 5 (G5). Lactate, glucose, acetate and creatinine were responsible for discriminating the control group from all the others CKD stages. Valine, alanine, glucose, creatinine, glutamate and lactate were responsible for the clustering of G1-G4 stages. G5 was discriminated by calcium ethylenediamine tetraacetic acid, magnesium ethylenediamine tetraacetic acid, creatinine, betaine/choline/trimethylamine N-oxide (TMAO), lactate and acetate. CKD G5 plasma pool which was submitted in MetaboAnalyst 4.0 platform (MetPA) analysis and showed 13 metabolic pathways involved in CKD physiopathology. Metabolic changes associated with glycolysis and gluconeogenesis allowed discriminating between CKD and control patients. The determination of involved molecules in TMAO generation in G5 suggests an important role in this uremic toxin linked to CKD and cardiovascular diseases. The aforementioned results propose the feasibility of metabolic assessment of CKD by NMR during treatment and disease progression.