The association between metabolomic profiles of lifestyle and the latent phase of incident chronic kidney disease in the UK Population.

Chronic kidney disease (CKD) is a global health challenge associated with lifestyle factors such as diet, alcohol, BMI, smoking, sleep, and physical activity. Metabolomics, especially nuclear magnetic resonance(NMR), offers insights into metabolic profiles' role in diseases, but more research is needed on its connection to CKD and lifestyle factors. Therefore, we utilized the latest metabolomics data from the UK Biobank to explore the relationship between plasma metabolites and lifestyle factors, as well as to investigate the associations between various factors, including lifestyle-related metabolites, and the latent phase of CKD onset. The study enrolled approximately 500,000 participants from the UK Biobank (UKB) between 2006 and 2010, excluding 447,163 individuals with missing data for any metabolite in the NMR metabolomics, any biomarker in the blood chemistry (including eGFR, albumin, or cystatin C), any factor required for constructing the lifestyle score, or a baseline diagnosis of CKD. Lifestyle scores (LS) were calculated based on several factors, including diet, alcohol consumption, smoking, BMI, physical activity, and sleep. Each healthy lifestyle component contributed to the overall score, which ranged from 0 to 6. A total of 249 biological metabolites covering multiple categories were determined by the NMR Metabolomics Platform. Random forest algorithms and LASSO regression were employed to identify lifestyle-related metabolites. Subsequently, accelerated failure time models(AFT) were used to assess the relationship between multiple factors, including traditional CKD-related biomarkers (such as eGFR, cystatin C, and albumin) and lifestyle-related metabolites, with the latent phase of incident CKD. Finally, we performed Kaplan-Meier survival curve analysis on the significant variables identified in the AFT model. Over a mean follow-up period of 13.86 years, 2,279 incident chronic kidney disease (CKD) cases were diagnosed. Among the 249 metabolites analyzed, 15 were identified as lifestyle-related, primarily lipid metabolites. Notably, among these metabolites, each 1 mmol/L increase in triglycerides in large LDL particles accelerated the onset of CKD by 24%. Diabetes, hypertension, and smoking were associated with a 56.6%, 31.5% and 22.3% faster onset of CKD, respectively. Additionally, each unit increase in age, BMI, TDI, and cystatin C was linked to a 3.2%, 1.4%, 1.6% and 32.3% faster onset of CKD. In contrast, higher levels of albumin and eGFR slowed the onset of CKD, reducing the speed of progression by 3.0% and 3.9% per unit increase, respectively. Nuclear magnetic resonance metabolomics offers new insights into renal health, though further validation studies are needed in the future.