Kidney Week

Abstract: FR-OR57

Adiposity and Obesity-Related Metabolomics: The CRIC Study

Session Information

• Findings from Landmark Trials, Other Kidney Trials, and Observational Studies
  November 05, 2021 | Location: Simulive, Virtual Only
  Abstract Time: 04:30 PM - 06:00 PM

Category: Health Maintenance, Nutrition, and Metabolism

• 1300 Health Maintenance, Nutrition, and Metabolism

Authors

• Zheng, Zihe, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States

Zihe Zheng, MD, MS, PhD

• Feldman, Harold I., University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States

Harold I. Feldman,

• Anderson, Amanda Hyre, Tulane University, New Orleans, Louisiana, United States

Amanda Hyre Anderson,

• Rhee, Eugene P., Massachusetts General Hospital, Boston, Massachusetts, United States

Eugene P. Rhee,

• Rebholz, Casey, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States

Casey Rebholz,

• Yang, Wei, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States

Wei Yang,

• Waikar, Sushrut S., Boston University, Boston, Massachusetts, United States

Sushrut S. Waikar,

• Hsu, Jesse Yenchih, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States

Jesse Yenchih Hsu,

• Mehta, Rupal, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Rupal Mehta,

• Rosas, Sylvia E., Joslin Diabetes Center, Boston, Massachusetts, United States

Sylvia E. Rosas,

• Ricardo, Ana C., University of Illinois at Chicago, Chicago, Illinois, United States

Ana C. Ricardo,

• Hsu, Chi-yuan, University of California San Francisco, San Francisco, California, United States

Chi-yuan Hsu,

• Chen, Jing, Tulane University, New Orleans, Louisiana, United States

Jing Chen,

• Ramachandran, Vasan S., Boston University, Boston, Massachusetts, United States

Vasan S. Ramachandran,

• Nelson, Robert G., National Institutes of Health, Bethesda, Maryland, United States

Robert G. Nelson,

Group or Team Name

• CKD Biomarkers Consortium; CRIC Study

Background

Obesity and adiposity are associated with progression and complications of CKD, partially by altering lipid metabolism and homeostasis. However, the phenotypic- and molecular-level mechanisms underlying these associations are not well understood. We identified adiposity/obesity related (AOR) CKD subgroups and examined potential mediation of CKD progression by plasma metabolites.

Methods

Among 1,529 CRIC participants with metabolomics data (Broad Institute) we applied consensus clustering with K-means on 20 adiposity-obesity and comorbidity parameters to identify CKD subgroups. We examined mediation effects by 634 plasma metabolites on the associations of patient subgroups with CKD progression using Aalen additive hazards models. For those statistically significant mediators, we estimated the HRs of CKD progression for each 2-fold increment in metabolite level using Cox model.

Results

We discovered 3 AOR CKD subgroups (groups with low obesity/diabetes risk, high obesity risk, and high diabetes risk) associated with CKD progression. 79 metabolites were significant mediators (p<0.05) for this subgroup-outcome association. After Bonferroni correction (p<6.33×10^-4) and adjusting for eGFR, 11 metabolites were associated with a lower hazard and 9 with an increased hazard of CKD progression (Table). After additional adjustment for covariates, 4 metabolites remained statistically significantly associated with CKD progression.

Conclusion

We identified 3 clinically meaningful CKD subgroups driven by participant adiposity/obesity profiles and metabolites that mediated the association with the risk of CKD progression. Our findings provide insights into the pathophysiological link between obesity and CKD progression and may indicate potential therapeutic targets. Replication in other populations is needed.

Funding

• NIDDK Support