Abstract
Severe obesity is a major risk for chronic kidney disease (CKD). Early detection and careful monitoring of renal function are critical for the prevention of CKD during obesity, since biopsies are not performed in patients with CKD and diagnosis is dependent on the assessment of clinical parameters. To explore whether distinct lipid and metabolic signatures in obesity may signify early stages of pathogenesis toward CKD, liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-high resolution accurate mass-mass spectrometry (GC-HRAM-MS) analyses were performed in the serum and the urine of severely obese patients with and without CKD. Moreover, the impact of bariatric surgery (BS) in lipid and metabolic signature was also studied, through LC-MS and GC-HRAM-MS analyses in the serum and urine of patients with severe obesity and CKD before and after undergoing BS. Regarding patients with severe obesity and CKD compared to severely obese patients without CKD, serum lipidome analysis revealed significant differences in lipid signature. Furthermore, serum metabolomics profile revealed significant changes in specific amino acids, with isoleucine and tyrosine, increased in CKD patients compared with patients without CKD. LC-MS and GC-HRAM-MS analysis in serum of patients with severe obesity and CKD after BS showed downregulation of levels of triglycerides (TGs) and diglycerides (DGs) as well as a decrease in branched-chain amino acid (BCAA), lysine, threonine, proline, and serine. In addition, BS removed most of the correlations in CKD patients against biochemical parameters related to kidney dysfunction. Concerning urine analysis, hippuric acid, valine and glutamine were significantly decreased in urine from CKD patients after surgery. Interestingly, bariatric surgery did not restore all the lipid species, some of them decreased, hence drawing attention to them as potential targets for early diagnosis or therapeutic intervention. Results obtained in this study would justify the use of comprehensive mass spectrometry-based lipidomics to measure other lipids aside from conventional lipid profiles and to validate possible early markers of risk of CKD in patients with severe obesity.
Highlights
According to World Health Organization, in 2016, over 55 million adults suffered from severe obesity supporting the current consideration of obesity as a global pandemic [1,2]
There are no published studies that cover this combination of factors of severe obesity and chronic kidney disease (CKD) with these metabolomics approaches in serum and urine
The analysis of the serum metabolome by liquid chromatography-mass spectrometry (LC-MS) and GC-HRAM-MS revealed that CKD patients with severe obesity presented a significant increase in the circulating levels of different TGs, DGs, PEs, PCs, LysoPCs, suggesting a distinguishing signature for the lipidome in these patients with renal damage
Summary
According to World Health Organization, in 2016, over 55 million adults suffered from severe obesity supporting the current consideration of obesity as a global pandemic [1,2]. There are no reliable markers of risk for early detection of CKD in patients with severe obesity. Biopsies are not performed in patients with CKD and diagnosis is dependent on the assessment of various clinical parameters [5]. All this importantly contributes to the fact that there is a high prevalence of undiagnosed patients with CKD, especially in those undiagnosed with other comorbidities [6]. It is imperative to find early markers in order to improve CKD diagnosis, so that these individuals may benefit from early interventions in order to prevent the development and/or progression of CKD
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