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Kidney Week

Abstract: TH-PO855

Biomarker Identification Using Serum Proteomics in Patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Session Information

Category: Genetic Diseases of the Kidneys

  • 1001 Genetic Diseases of the Kidneys: Cystic

Authors

  • Arjune, Sita, Department 2 of Internal Medicine, Renal Division; University of Cologne, Cologne, Germany
  • Späth, Martin R., Department 2 of Internal Medicine, Renal Division; University of Cologne, Cologne, Germany
  • Rauen, Thomas, University Hospital Aachen, Aachen, Germany
  • Mueller, Stefan, Center for Molecular Medicine Cologne, Cologne, Germany
  • Schermer, Bernhard, Department 2 of Internal Medicine, Renal Division; University of Cologne, Cologne, Germany
  • Benzing, Thomas, Department 2 of Internal Medicine, Renal Division; University of Cologne, Cologne, Germany
  • Burst, Volker Rolf, Department 2 of Internal Medicine, Renal Division; University of Cologne, Cologne, Germany
  • Grundmann, Franziska, Department 2 of Internal Medicine, Renal Division; University of Cologne, Cologne, Germany
  • Mueller, Roman-Ulrich, Department 2 of Internal Medicine, Renal Division; University of Cologne, Cologne, Germany
Background

The variable course of autosomal dominant polycystic kidney disease (ADPKD) makes it important to identify biomarkers that predict disease progression to allow optimal counseling and selection of patients for targeted therapies. Currently, MRI-based volumetric analysis is used as a standard diagnostic tool. In order to identify easily measurable biomarkers of ADPKD progression, we used mass spectrometric quantification of the serum proteome.

Methods

Hence, serum proteome analysis was performed by MALDI-TOF MS using label-free quantification. We compared ADPKD patients (n = 292) with healthy control subjects (n = 58) and IgA nephritis patients (n = 30) as an independent CKD control. Randomization of the samples was achieved using random sampling. For data evaluation normalized log2 transformed intensities were used and proteins were examined for their distribution in different patient groups (e.g. age, CKD stage, Mayo class). Clinical data of all patients were available from the AD(H)PKD registry.

Results

Mass spectrometric analysis of the serum proteome in ADPKD patients revealed differential expression of 19 proteins compared to healthy control subjects (q<0.05), 8 of these proteins also differed from IgA nephritis patients suggesting specificity for ADPKD. The identified proteins could be assigned to the regulatory pathways of IGF activity and hemostasis.

Conclusion

These results provide valuable insights into the alterations of the serum proteome in ADPKD and indicate that selected serum proteome markers may contribute to the improvement of ADPKD management and disease severity assessment in the future. The newly identified markers will now be investigated for their predictive potential and their role in the pathogenesis of ADPKD.