Abstract: TH-PO402

IL-1 Inhibition Improves HDL Functionality in CKD

Session Information

Category: Nutrition, Inflammation, and Metabolism

  • 1401 Nutrition, Inflammation, Metabolism

Authors

  • Hung, Adriana, Vanderbilt University, Nashville, Tennessee, United States
  • Kon, Valentina, Vanderbilt University, Nashville, Tennessee, United States
  • Tsuchida, Yohei, Vanderbilt University, Nashville, Tennessee, United States
  • Nowak, Kristen L., University of Colorado Denver: Anschutz Medical Campus, Aurora, Colorado, United States
  • Sarkar, Sudipa, Vanderbilt University, Nashville, Tennessee, United States
  • Stewart, Thomas G., Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Chonchol, Michel, University of Colorado, Aurora, Colorado, United States
  • Huang, Jiansheng, Vanderbilt University, Nashville, Tennessee, United States
  • Linton, Macrae F., Vanderbilt University School of Medicine, Nashville, Tennessee, United States
  • Ikizler, Talat Alp, Vanderbilt University Medical Center, Nashville, Tennessee, United States
Background

Cardiovascular disease (CVD) is the most prominent cause of morbidity and mortality among patients with chronic kidney disease (CKD). Inflammation and oxidative stress are considered to contribute to CVD in CKD. Both of these factors are also known promote HDL malfunction in CKD. Whether interventions that modulate systemic inflammation can improve anti-inflammatory aspects of HDL in the setting of advanced CKD or ESRD is unknown.

Methods

We conducted a post-hoc analysis to evaluate if IL-1 blockade could improve the anti-inflammatory and anti-oxidant functions of HDL in patients with CKD. We used serum samples from two pilot randomized clinical trials; one in CKD stages 3 & 4 patients (CKD3/4) and one in maintenance hemodialysis (MHD) patients. HDL was isolated from each participant’s serum at baseline and at the end of the study. The anti-inflammatory and anti-oxidant function of HDL was measured as the response of LPS-activated THP-1 macrophages exposed to the participant’s HDL (IL-6, TNF-α, NLRP3 response were measured by RT-PCR and cellular oxidant production by HPLC). Biomarkers were log transformed and repeated measures ANCOVA was used to estimate the percent change in biomarker expression with the intervention (btween group comparison).

Results

The mean age of the participants was 60±13, 72% (n=33) were male, 38% (n=17) were black. There were 32 CKD patients (16 intervention and 16 placebo) and 14 MHD (7 intervention and 7 CKD). IL-1 blockade down-regulated hsCRP and IL-6 in both studies (Nowak et al 2017 and Hung et al 2011). IL-1 blockade effectively improved HDL functionality: compared to baseline, IL-1 blockade reduced TNF expression by 30% (p=0.006) [18% in CKD (p=0.03) and 61% in MHD (p=0.06)], IL-6 by 40% (p=0.02) [36% in CKD (p=0.006) and 50% in MHD (p=0.3)], and NLRP3 by 17% (p=0.02) [15% in CKD (p=0.02) and 25% in MHD (p=0.02)]. Cellular superoxide production fell by 15% (p<0.001) [17% in CKD (p< 0.001) and 12% in MHD (p=0.004)].

Conclusion

IL-1 blockade improved the anti-inflammatory and anti-oxidative properties of HDL in patients with CKD stage 3 or stage 4 and MHD. Larger scale and longer term prospective studies are needed to confirm the utility of this intervention in clinical settings.
(Hung and Tsuchida are first co-authors)

Funding

  • Veterans Affairs Support