Presentation description

Chronic kidney disease (CKD) disproportionately impacts Native Hawaiian and Pacific Islander (NHPI) Communities, where there are nearly 2,000 new cases of CKD per million per year in NHPI communities (double that of African American and nearly 10 times that of white Americans). Mitochondrial dysfunction is hypothesized to be a key contributing factor in developing overt CKD in humans. However, there are no established mouse models which recapitulate the pathology of CKD in humans, thus limiting the ability to study CKD. Therefore, the purpose of this ongoing research study is to establish a mouse model of CKD using a high-fat high-salt (HF/HS) diet and investigate the impacts of a HF/HS diet on kidney mitochondrial function. Compared to chow-fed mice, mice fed a HF/HS diet for 8 weeks exhibited unaltered maximal mitochondrial respiration (Chow: 2101.0 ± 410.3 pmolO2/sec/mg; HF/HS: 1683.5 ± 280.2 pmolO2/sec/mg; p = 0.39). However, ATP production under submaximal ADP concentrations was ~40% lower in HF/HS-fed mice (Chow: 4656.4 ± 911.1 pmolATP/sec/mg; HF/HS: 2860.3 ± 653.5 pmolATP/sec/mg; p = 0.14). Despite the lower ATP production, non-significant impairments in submaximal O2 consumption resulted in unaltered P:O ratio (Chow: 2.39 ± 0.1; HF/HS: 3.36 ± 0.5; p = 0.18). In conclusion, our preliminary research shows promising evidence that 8 weeks of a HF/HS diet induces mitochondrial dysfunction in mouse kidneys, which may precede CKD in these animals. These findings provide insight into the underlying pathologies of CKD and may be used to better understand the disproportionate prevalence of CKD in NHPI communities.