ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

ASN / Education & Meetings / Kidney Week /

Please note that you are viewing an archived section from 2022 and some content may be unavailable. To unlock all content for 2022, please visit the archives.

Abstract: SA-PO918

Treatment With Nicotinamide Riboside Alters Systemic Mitochondrial Metabolism Without Impacting Exercise Capacity in Patients With CKD

Session Information

Category: CKD (Non-Dialysis)

  • 2202 CKD (Non-Dialysis): Clinical‚ Outcomes‚ and Trials

Authors

  • Ahmadi, Armin, University of California Davis, Davis, California, United States
  • Begue, Gwenaelle, California State University Sacramento, Sacramento, California, United States
  • Valencia, Ana Patricia, University of Washington, Seattle, Washington, United States
  • Norman, Jennifer E., University of California Davis, Davis, California, United States
  • Marcinek, David J., University of Washington, Seattle, Washington, United States
  • Van Doren, Matthew P., Fred Hutchinson Cancer Research Center, Seattle, Washington, United States
  • Prince, David K., University of Washington, Seattle, Washington, United States
  • Kestenbaum, Bryan R., University of Washington, Seattle, Washington, United States
  • Roshanravan, Baback, University of California Davis, Davis, California, United States
Background

The impact of therapies that target mitochondrial function in CKD is still unknown. We conducted a clinical trial of coenzyme Q10 (CoQ10) and nicotinamide riboside (NR) to determine their impact on endurance exercise capacity and metabolic profile in CKD patients.

Methods

We conducted a placebo-controlled, double blind, cross-over trial with 3 arms: placebo, CoQ10, and NR. Adults aged between 30-79 with moderate-severe CKD (N=25), eGFR of <60ml/min/1.73m2, were recruited. Subjects received NR (1000 mg/day) or CoQ10 (1200 mg/day) for 6 weeks. Maximal aerobic capacity (VO2 peak) was assessed using a graded cycle exercise test. Plasma samples underwent semi-targeted metabolomics profiling using gas chromatography. Impact of treatment on VO2 peak was assessed statistically using ANOVA. Linear mixed effects modeling was used to estimate differences in plasma metabolites

Results

Participants mean age was 61.0+/-11.6 with a mean eGFR of 36.9+/-9.2. Females comprised 40% of the cohort with a 16% prevalence of diabetes. CoQ10 and NR treatment had no impact on VO2 peak (p=0.37, p=0.38 respectively) (Figure 1A). A total of 13 out of the 98 detected metabolites were significantly altered in response to NR treatment. These metabolites were predominantly involved in TCA cycle and amino acid metabolism (Figure 1B). All noted metabolites significantly increased compared to placebo except for two TCA cycle intermediates (α-KG and malate). Only 2 metabolites were significantly altered post CoQ10 treatment compared to placebo.

Conclusion

NR treatment alters systemic mitochondrial metabolism but had no meaningful impact on aerobic capacity in CKD. Future studies will focus on treatment associated changes in the mitochondrial transcriptome and other performance-based outcomes.

Figure 1. Impact of CoQ10 and NR on VO2 peak compared to placebo (A). Pathway analysis of changes with NR treatment compared to placebo (B).

Funding

  • NIDDK Support