Urinary Metabolomic Changes Accompanying Albuminuria Remission following Gastric Bypass Surgery for Type 2 Diabetic Kidney Disease

• Published in: Metabolites Vol. 12; no. 2; p. 139
• Main Authors: Martin, William P, Malmodin, Daniel, Pedersen, Anders, Wallace, Martina, Fändriks, Lars, Aboud, Cristina M, Petry, Tarissa B Zanata, Cunha da Silveira, Lívia P, da Costa Silva, Ana C Calmon, Cohen, Ricardo V, le Roux, Carel W, Docherty, Neil G
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 02.02.2022; MDPI
• Subjects: Albuminuria; Bariatric surgery; BCAA; Blood glucose; Blood pressure; Catabolites; Chronic kidney disease; Creatinine; Diabetes; Diabetes mellitus; Diabetic kidney disease; Endocrinology and Diabetes; Endokrinologi och diabetes; Ethnicity; Gastric bypass; Gastroenterologi; Gastroenterology and Hepatology; Gastrointestinal surgery; Glucose; Glutamine; Heart surgery; Kidney diseases; Metabolism; Metabolites; Metabolomics; Microvasculature; NMR spectroscopy; Obesity; Patients; Phenylalanine; Remission; Remission (Medicine); Sucrose; Surgery; Triglycerides; Trimethylamine; Type 2 diabetes; Tyrosine; Valine; Weight control; White people; γ-Aminobutyric acid; diabetic kidney disease; albuminuria; chronic kidney disease; bariatric surgery; type 2 diabetes; metabolomics; NMR spectroscopy; BCAA; gastric bypass; obesity
• ISSN: 2218-1989; 2218-1989
• DOI: 10.3390/metabo12020139

In the Microvascular Outcomes after Metabolic Surgery randomised clinical trial (MOMS RCT, NCT01821508), combined metabolic surgery (gastric bypass) plus medical therapy (CSM) was superior to medical therapy alone (MTA) as a means of achieving albuminuria remission at 2-year follow-up in patients with obesity and early diabetic kidney disease (DKD). In the present study, we assessed the urinary H-NMR metabolome in a subgroup of patients from both arms of the MOMS RCT at baseline and 6-month follow-up. Whilst CSM and MTA both reduced the urinary excretion of sugars, CSM generated a distinctive urinary metabolomic profile characterised by increases in host-microbial co-metabolites (N-phenylacetylglycine, trimethylamine N-oxide, and 4-aminobutyrate (GABA)) and amino acids (arginine and glutamine). Furthermore, reductions in aromatic amino acids (phenylalanine and tyrosine), as well as branched-chain amino acids (BCAAs) and related catabolites (valine, leucine, 3-hydroxyisobutyrate, 3-hydroxyisovalerate, and 3-methyl-2-oxovalerate), were observed following CSM but not MTA. Improvements in BMI did not correlate with improvements in metabolic and renal indices following CSM. Conversely, urinary metabolites changed by CSM at 6 months were moderately to strongly correlated with improvements in blood pressure, glycaemia, triglycerides, and albuminuria up to 24 months following treatment initiation, highlighting the potential involvement of these shifts in the urinary metabolomic profile in the metabolic and renoprotective effects of CSM.