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Abstract: TH-PO416

Kynurenines and Change in Body Mass Index in Autosomal Dominant Polycystic Kidney Disease

Session Information

Category: Genetic Diseases of the Kidneys

  • 1201 Genetic Diseases of the Kidneys: Cystic

Authors

  • Nowak, Kristen L., University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
  • You, Zhiying, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
  • Steele, Cortney, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
  • Gitomer, Berenice Y., University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
  • Chonchol, Michel, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
  • Klawitter, Jelena, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
Background

We have previously described that overweight and obesity are associated with kidney disease progression in individuals with early-stage autosomal dominant polycystic kidney disease (ADPKD). We have also reported dysregulated kynurenine metabolism, which associated with kidney disease severity, in early-stage patients with ADPKD. As the tryptophan-kynurenine pathway has been reported to be dysregulated in obesity, and kynurenines can induce and potentiate oxidative stress and inflammation, we hypothesized that baseline kynurenine circulating concentrations would associate with change in BMI patients with ADPKD.

Methods

357 participants with ADPKD and estimated glomerular filtration rate (eGFR) >60 ml/min/1.73m2 who participated in HALT Study A and had repeated measurements of kynurenines, BMI, and covariates were included. Twelve key tryptophan metabolites were previously measured in plasma using a validated liquid chromatography-mass spectrometry assay. The time-varying associations between kynurenines (individual mean and mean change over time) and change in BMI over 48-months were assessed using linear mixed effects regression models.

Results

Mean+s.d. age was 38±8 years, eGFR was 90±17 ml/min/1.73m2, and height-adjusted total kidney volume was 724±413 ml/m2, baseline BMI was 27.0±4.8 kg/m2. Greater individual log-transformed mean concentrations of kynurenic acid (b-estimate 1.71 [0.41, 3.01]), and quinolinic acid (β-estimate 2.13 [0.00, 4.25) and a lower log-transformed mean change in picolinic acid over time (β-estimate -0.52 [-0.13, -0.95]) were associated with greater increase in BMI after adjustment for demographics, study randomization, eGFR, baseline height-adjusted kidney volume, and genotype.

Conclusion

Several kynurenines were associated with change in BMI in ADPKD patients. Further research should evaluate whether kynurenines could serve as a biomarker of obesity-associated kidney growth in patients with ADPKD.

Funding

  • NIDDK Support