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Metabolomic and lipidomic profiles of CKD in obese patients in serum and urine (part 1 of 3)

ABSTRACT: Obesity is a global pandemic with an increase prevalence over the years. This condition elevates the risk of developing cardiovascular diseases, hypertension and renal pathologies, like chronic kidney disease (CKD). In the present study, the metabolomic and the lipidomic profiles of CKD obese patients were analyzed comparing with obese subjects without CKD. Subsequently, CKD obese patients underwent bariatric surgery and the effect of surgery in the CKD progression of these subjects was evaluated. Serum and urine were measured by LC-MS and GC-HRAM equipment.

ORGANISM(S): Human Homo Sapiens

TISSUE(S): Blood

DISEASE(S): Obesity

SUBMITTER: Borja Lanzon

PROVIDER: ST001824 | MetabolomicsWorkbench | Fri Apr 02 00:00:00 BST 2021

REPOSITORIES: MetabolomicsWorkbench

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Project description:Background & Aims: Bariatric surgery is associated with improved outcomes in subjects with severe obesity. We aimed to determine the prognostic relevance of liver histology in a large cohort of obese patients undergoing bariatric surgery. Methods: In a single center cohort of 492 subjects undergoing Roux-en-Y gastric bypass bariatric surgery with routine perioperative liver biopsy at Geneva University Hospital between January 1997 to December 2004, clinical and histopathological variables were analyzed for association with overall survival. Survival of the cohort was compared to age- and sex-matched life tables from the Swiss general population and propensity score-matched subjects from the third National Health and Nutrition Examination Survey (NHANES III). A 32-gene signature was evaluated in the liver tissue of 47 non-alcoholic steatohepatitis (NASH) subjects. Results: Median body mass index was 43.6 kg/m2. Twenty-one patients (4.2%) died during a median follow-up of 10.3 years. At baseline liver histology, 12% and 16% of subjects had NASH, and fibrosis, respectively. In multivariable Cox regression, presence of NASH (hazard ratio [HR] 3.4, p=0.0087), age greater than 50 years (HR 2.7, p=0.044), hypertension (HR 3.8, p=0.021), and short-term postoperative complications (HR 2.8, p=0.048) were associated with overall survival. Compared to matched NHANES III subjects, bariatric surgery improved long-term survival (HR 0.54, p=0.035), although this benefit was not observed in the subgroup of NASH patients (HR 0.97, p=0.94). A 32-gene poor prognosis signature prediction was associated with worse overall survival within NASH subjects (n=47, HR = 7.7, p=0.03 ). Conclusions Histologically proven NASH was associated with increased long-term mortality in subjects undergoing bariatric surgery. Although survival benefit of bariatric surgery may be limited in obese patients with NASH, a 32-gene expression signature appears to predict long term mortality in these patients.