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Kidney Week

Abstract: PO1255

Metabolomic Changes over 1 Year Following Drug or Lifestyle Interventions in Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Session Information

Category: Genetic Diseases of the Kidneys

  • 1001 Genetic Diseases of the Kidneys: Cystic

Authors

  • Steele, Cortney, University of Colorado - Anschutz Medical Campus, Aurora, Colorado, United States
  • Klawitter, Jelena, University of Colorado - Anschutz Medical Campus, Aurora, Colorado, United States
  • Wang, Wei, University of Colorado - Anschutz Medical Campus, Aurora, Colorado, United States
  • You, Zhiying, University of Colorado - Anschutz Medical Campus, Aurora, Colorado, United States
  • Catenacci, Victoria, University of Colorado - Anschutz Medical Campus, Aurora, Colorado, United States
  • Struemph, Taylor, University of Colorado - Anschutz Medical Campus, Aurora, Colorado, United States
  • George, Diana, University of Colorado - Anschutz Medical Campus, Aurora, Colorado, United States
  • Gitomer, Berenice Y., University of Colorado - Anschutz Medical Campus, Aurora, Colorado, United States
  • Brosnahan, Godela M., University of Colorado - Anschutz Medical Campus, Aurora, Colorado, United States
  • Chonchol, Michel, University of Colorado - Anschutz Medical Campus, Aurora, Colorado, United States
  • Nowak, Kristen L., University of Colorado - Anschutz Medical Campus, Aurora, Colorado, United States
Background

Autosomal dominant polycystic kidney disease (ADPKD) is the most commonly inherited progressive kidney disease. Studies have shown differences in metabolomic profiles in those with ADPKD; however few studies assess change over time.

Methods

We performed metabolomics to assess patterns of change across four groups of participants with APDKD pooled from 2 randomized clinical trials: placebo control (CON), metformin (1,000/mg/day) (MET), intermittent fasting (IMF; 3 day/wk of 80% energy restriction from baseline weight maintenance requirements), and daily caloric restriction (DCR, daily restriction of 34% per day from baseline weight maintenance requirements). Analyzed plasma samples were collected during the trials at baseline and 1 -year for each group. A total of 163 metabolites were measured using liquid chromatography-mass spectrometry (LC-MS). Differences in metabolomic profiles over time and within study groups were evaluated by a one-way ANOVA and Bonferroni correction for multiple comparisons.

Results

Baseline characteristics for each trial included CON (n=22, 14 female (F), 49±7 yrs of age (mean±s.d.), estimated glomerular filtration rate [eGFR] 73±13 ml/min/1.73m2, body mass index (BMI) 28.3±4 kg/m2), MET (n=22, 14 F, 48±7 yrs of age, eGFR 69±14 ml/min/1.73m2, BMI 29.7±7 kg/m2), IMF (n=10, 5 F, 47±6 yrs of age, eGFR 77±16 ml/min/1.73m2, BMI 34.6±5 kg/m2), and DCR (n=9, 5 F, 46±13 yrs of age, eGFR 68±21 ml/min/1.73m2, BMI 34.1±5 kg/m2). Age and eGFR did not differ between groups. BMI was higher in the IMF compared to CON (p=0.031). Metabolite changes are depicted in Figure 1.

Conclusion

There are changes at one year in metabolites in adults with ADPKD between control, metformin, intermittent fasting, and daily caloric interventions. Further research is needed to identify metabolomic profile shifts involving drug and dietary interventions.

Percent Δ of metabolites. Values are expressed as mean ± SD.

Funding

  • NIDDK Support