(880.3) Sleep Apnea and Kidney Disease: The Role of Hypoxia and Lysyl Oxidase

Poster Board Number: E271

Ann Thomas (College of Medicine, University of Florida), Nishka Jakkidi (College of Medicine, University of Florida), Shiyu Li (College of Medicine, University of Florida), Kit-Yan Cheng (College of Medicine, University of Florida), Michelle Gumz (College of Medicine, University of Florida), Muna Canales (College of Medicine, University of Florida), Rajesh Mohandas (College of Medicine, University of Florida)

Study Objective/Hypothesis

Chronic kidney disease (CKD) or progressive loss of kidney function, is a serious health condition that affects 1 in 7 adults or an estimated 37 million Americans. Epidemiological studies have linked CKD with Sleep Apnea (SA), a breathing disorder characterized by erratic breathing, and episodes of hypoxia. However, the mechanisms that underlie the association between CKD and SA are not well understood. Hypoxia Inducible Factor-1α (HIF-1α) is a transcription factor that regulates the body’s response to hypoxia. Lysyl oxidase and lysyl oxidase likes (LOX and LOX-Ls) are a group of copper enzymes that are hypoxia responsive and pro-fibrotic. We hypothesized that hypoxia in SA upregulates HIF-1α to drive expression of LOX or LOX-L enzymes, fibrosis, and CKD.

Materials amp; Methods

Samples from the Sleep and Nephrology and Outcomes Research Study (SNORE), a prospective observational study of sleep disorders in veterans with CKD, were used for this study. The patients were divided into three main groups: CKD with no SA (n=14), CKD with severe SA (n=12) and healthy controls (n=13). RNA from peripheral blood mononuclear cells (PBMC) was isolated using PAXGene Blood RNA tubes (Qiagen). The RNA was then used as a template for reverse transcription, converting it into cDNA and fold changes in gene expression between groups were examined using real time PCR. Differences between groups were compared using nonparametric Mann Whitney U tests and a p-value lt; 0.05 was considered statistically significant.

Results

LOX expression was lower in patients with CKD compared to healthy controls, regardless of SA (CKD with SA: 0.28 ± 0.06 (p=0.04) and CKD without SA: 0.33 ± 0.07 (p=0.09)). There were no significant differences seen in any of the LOX-L expression (LOX-L1 (p=0.84), LOX-L2 (p=0.35), or LOX-L3 (p=0.93)). Similarly, HIF-1α was lower in patients with CKD (CKD with SA: 0.69 ± 1.0 (p=0.47) and CKD without SA: 0.46 ± 0.06 (p=0.01)). There was no statistically significant correlation between LOX and HIF-1α (r=0.04, p=0.83).

Conclusion

Our results showed that HIF-1α and LOX expression in PBMC was decreased in patients with CKD regardless of if they had SA or not. The mechanisms underlying these observations, the functional significance, and if these changes are representative of tissue LOX expression needs further studies.