Dr. Yi Huang (UMBC) and Dr. Michael Domanski (University of Maryland School of Medicine, UMB) have been awarded an Accelerated Translational Incubator Pilot (ATIP) grant. The program is administered by UMB's Institute for Clinical & Translational Research.
Title of the project: Evaluation of the Effect of Serum Lipid Levels on the Progression of Renal Dysfunction
Abstract: Chronic kidney disease (CKD) is common (approximate 15% of US adults estimated by CDC) and is associated with significant disability, reduced quality of life and diminished longevity. The extent to which various lipid fractions, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein, and triglycerides are independent risk factors for progressive renal dysfunction is unknown. For CKD prevention and new treatment/ intervention development, the key question is to identify strong and potentially reversible risk factor(s) for the progression of renal dysfunction. This is the motivation for focusing on serum lipid levels and the impetus for this project.
The “lipid nephrotoxicity hypothesis” suggests that hyperlipidemia and proteinuria cause progressive renal disease.4 Even though a few studies report correlations between a specific lipid fraction and estimated glomerular filtration rate (eGFR) [2,3,4,7,8,9,11], they did not address the long term cumulative lipid exposure risks on renal functions. We develop two new metrics to characterize the shapes of the time trajectories of lipid levels over age – cumulative lipid exposure measure and the rate of lipid exposure changes over time, explained in page 3 of “Research Plan” file. These two measures will provide new insights into how lipids influence renal function. For example, the effect evaluation of cumulative lipid exposure on progression of renal dysfunction could be employed to assess whether treatments on lipid abnormalities in early age will help the slow CKD development in later stages of life. Despite the lack of research on the cumulative exposure and rate of exposure change of various lipid fractions’ effect on renal function, such studies are of great importance for advancing our understanding of the relationship between abnormalities of lipid levels and the development of CKD, which is translational to clinical practice. For example, using cumulative triglycerides in combination with other risk factors may identify the vulnerable subgroup susceptive to CKD, which would allow practitioners to target early health inventions for more efficacious prevention.
This project will examine whether serum lipid levels are risk factors for the progression of renal dysfunction and whether cumulative exposure and/or the time course (trajectory) of area accumulation impacts risk. The Coronary Artery Risk Development in Young Adults (CARDIA) Study, a multicenter longitudinal cohort study that followed a large diverse population for 30 years1, will be used as it contains comprehensive data to support our project. This study greatly empowers our project to conduct a systematic evaluation of the effects of various lipid fractions, especially the cumulative lipid exposures, on progressive renal dysfunction. We anticipate this will lead to important discoveries into the modalities of lipid levels’ influence on renal function. Access portions of the CARDIA data at UMBC confirmed the applicability of the dataset. My access to all the CARDIA data needed for this project has been granted.