Metabolomic Changes After Bariatric Surgery Adjusted for Glomerular Filtration Rate Suggest Mechanisms of Kidney Protection.

Abstract

This study aimed to characterize bariatric surgery-induced changes in serum metabolites while accounting for changes in glomerular filtration rate (GFR) to understand the metabolic benefits to the kidney of bariatric surgery. This was a prospective, single-center cohort of 27 adults with severe obesity who underwent bariatric surgery. Serum metabolomics and measured GFR (mGFR) were performed 1-3 months prior to and 6 months after surgery. In generalized estimating equation (GEE) models, we examined bariatric surgery- and mGFR-associated changes in serum metabolites. We used MetaboAnalyst to perform pathway analyses. Bariatric surgery was significantly associated with changes in 223 serum metabolites after adjustment. Following bariatric surgery, several pathways were downregulated (alpha-linoleic acid and linoleic acid, methionine, kynurenine, and alanine-glucose metabolism pathways; raw p < 0.05) or upregulated (phenylacetate, bile acid biosynthesis, taurine and hypo-taurine metabolism, porphyrin metabolism pathways; raw p < 0.05). Creatinine demonstrated a significant mGFR-independent decrease following surgery. The top metabolites significantly associated with mGFR included N,N,N-trimethyl-alanyl proline betaine (TMAP), followed by creatinine. We discovered several GFR-independent metabolomic changes after bariatric surgery which may underlie its beneficial kidney effects including decreased inflammation, oxidation, and insulin resistance. Further studies are needed to investigate the potential mechanistic role of identified metabolites to clarify mechanisms of obesity-related kidney disease.