Lipidomic profiling in the Strong Heart Study identified American Indians at risk of chronic kidney disease

Authors

Wenjie Zeng
Habtamu B. Beyene
Mikko Kuokkanen, The University of Texas Rio Grande Valley
Guanhong Miao
Dianna J. Magliano
Jason G. Umans
Nora Franceschini
Joanne E. Curran, The University of Texas Rio Grande ValleyFollow
John Blangero, The University of Texas Rio Grande ValleyFollow

Document Type

Article

Publication Date

7-15-2022

Abstract

Dyslipidemia associates with and usually precedes the onset of chronic kidney disease (CKD), but a comprehensive assessment of molecular lipid species associated with risk of CKD is lacking. Here, we sought to identify fasting plasma lipids associated with risk of CKD among American Indians in the Strong Heart Family Study, a large-scale community-dwelling of individuals, followed by replication in Mexican Americans from the San Antonio Family Heart Study and Caucasians from the Australian Diabetes, Obesity and Lifestyle Study. We also performed repeated measurement analysis to examine the temporal relationship between the change in the lipidome and change in kidney function between baseline and follow-up of about five years apart. Network analysis was conducted to identify differential lipid classes associated with risk of CKD. In the discovery cohort, we found that higher baseline level of multiple lipid species, including glycerophospholipids, glycerolipids and sphingolipids, was significantly associated with increased risk of CKD, independent of age, sex, body mass index, diabetes and hypertension. Many lipid species were replicated in at least one external cohort at the individual lipid species and/or the class level. Longitudinal change in the plasma lipidome was significantly associated with change in the estimated glomerular filtration rate after adjusting for covariates, baseline lipids and the baseline rate. Network analysis identified distinct lipidomic signatures differentiating high from low-risk groups. Thus, our results demonstrated that disturbed lipid metabolism precedes the onset of CKD. These findings shed light on the mechanisms linking dyslipidemia to CKD and provide potential novel biomarkers for identifying individuals with early impaired kidney function at preclinical stages.

Comments

Original published version available at https://doi.org/10.1016/j.kint.2022.06.023

Recommended Citation

Zeng, W., Beyene, H. B., Kuokkanen, M., Miao, G., Magliano, D. J., Umans, J. G., ... & Zhao, J. (2022). Lipidomic profiling in the Strong Heart Study identified American Indians at risk of chronic kidney disease. Kidney International, 102(5), 1154-1166.

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.

Publication Title

Kidney International

DOI

10.1016/j.kint.2022.06.023

Academic Level

faculty

Mentor/PI Department

Office of Human Genetics