NMR-Based Metabolomics in Differential Diagnosis of Chronic Kidney Disease (CKD) Subtypes

Metabolites. 2022 May 28;12(6):490. doi: 10.3390/metabo12060490.

Abstract

Chronic Kidney Disease (CKD) is considered as a major public health problem as it can lead to end-stage kidney failure, which requires replacement therapy. A prompt and accurate diagnosis, along with the appropriate treatment, can delay CKD's progression, significantly. Herein, we sought to determine whether CKD etiology can be reflected in urine metabolomics during its early stage. This is achieved through the analysis of the urine metabolic fingerprint from 108 CKD patients by means of Nuclear Magnetic Resonance (NMR) spectroscopy metabolomic analysis. We report the first NMR-metabolomics data regarding the three most common etiologies of CKD: Chronic Glomerulonephritis (IgA and Membranous Nephropathy), Diabetic Nephropathy (DN) and Hypertensive Nephrosclerosis (HN). Analysis aided a moderate glomerulonephritis clustering, providing characterization of the metabolic fluctuations between the CKD subtypes and control disease. The urine metabolome of IgA Nephropathy reveals a specific metabolism, reflecting its different etiology or origin and is useful for determining the origin of the disease. In contrast, urine metabolomes from DN and HN patients did not reveal any indicative metabolic pattern, which is consistent with their fused clinical phenotype. These findings may contribute to improving diagnostics and prognostic approaches for CKD, as well as improving our understanding of its pathology.

Keywords: CKD; IgA; NMR spectroscopy; eGFR; glomerulonephritis; membranous; metabolomics; urine.

Grants and funding

The work was supported by the INSPIRED (MIS 5002550) and OMIC-ENGINE (MIS 5002636), which are implemented under the Action ‘Reinforcement of the Research and Innovation Infrastructure,’ funded by the Operational Program ‘Competitiveness, Entrepreneurship and Innovation’ (NSRF 2014–2020) and co-financed by Greece and the European Union (European Regional Development Fund). Additionally, EU FP7 REGPOT CT-2011-285950—“SEE-DRUG” project is acknowledged for the purchase of UPAT’s 700 MHz NMR equipment. PGT is supported by the NIHR Imperial Biomedical Research Centre (BRC).