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Abstract: TH-PO856

Urinary Adenosine and Adenosine/Xanthine Ratio Associate with the Rate of eGFR Decline in a Cohort of Patients with Autosomal Dominant Polycystic Kidney Disease

Session Information

Category: Genetic Diseases of the Kidneys

  • 1001 Genetic Diseases of the Kidneys: Cystic

Authors

  • Dekker, Shosha E.I., Leiden University Medical Center, Leiden, Netherlands
  • Sanchez-Lopez, Elena, Leiden University Medical Center, Leiden, Netherlands
  • Soonawala, Darius, Leiden University Medical Center, Leiden, Netherlands
  • Peters, Dorien J.M., Leiden University Medical Center, Leiden, Netherlands
  • Mayboroda, Oleg, Leiden University Medical Center, Leiden, Netherlands
  • De Fijter, Johan W., Leiden University Medical Center, Leiden, Netherlands
Background

The variable course of autosomal dominant polycystic kidney disease (ADPKD), and the advent of renoprotective treatment make it important to discover novel biomarkers for predicting renal disease progression. Based on in vivo data, we hypothesised that urinary ATP excretion is increased in ADPKD, which might contribute to disease progression. We applied urinary metabolomics to explore differences in purine metabolism compounds, as an indirect readout of ATP, and the association with estimated glomerular filtration rate (eGFR; CKD-EPI equation), and progressive loss of eGFR.

Methods

Targeted metabolic profiling using Liquid Chromatography-Mass Spectrometry was performed on single, spot urine samples of 187 ADPKD patients (mean age 48±10 years, 53% female, mean eGFR 53±20 ml/min/1.73m2), and 139 other chronic, renal disease patients (mean age 56±17 years, 48% female, mean eGFR 54±33 ml/min/1.73m2). Multiple regression analysis was used to describe the association between a pre-selected set of the metabolites and actual eGFR, and annual change in eGFR.

Results

Abundancies of adenosine, inosine, hypoxanthine, xanthine, and uric acid were determined and normalized. For all metabolites, no differences were found between ADPKD and non-ADPKD patients. Adenosine was most strongly associated with eGFR in the total cohort (F=92.35, P<2.2e-16, r2=0.222) as well as in patients with ADPKD. In ADPKD, we additionally evaluated the association with rate of eGFR progression over time. For 131 patients (mean age 49±7 years, 50% female, mean eGFR 49±11 ml/min/1.73m2, mean eGFR decline -3.4±-2.7 ml/min/1.73m2 per year), sequential eGFR data were available. Linear regression analysis showed that the combination of adenosine and the adenosine/xanthine ratio had the strongest association with annual change in eGFR (F=6.70, P=0.002, r2=0.095). Moreover, this model had additional value beyond that of baseline eGFR, age and/or total kidney volume.

Conclusion

In this pilot study, urinary adenosine and adenosine/xanthine ratio were associated with the rate of eGFR decline in patients with ADPKD. Validation of these findings is needed in a larger cohort with a varied distribution in rate of renal function decline.

Funding

  • Other NIH Support