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Abstract: FR-PO441

Identification of New Protein Biomarkers for Diabetic Kidney Disease by Proximity Extension Assays

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Thorenz, Anja, Bayer AG, Wuppertal, Germany
  • Hocher, Berthold, University of Potsdam, Potsdam, Germany
  • Tsuprykov, Oleg, University of Potsdam, Potsdam, Germany
  • Pavkovic, Mira, Bayer AG, Wuppertal, Germany
Background

Diabetic kidney disease (DKD) is a complication of diabetes and the leading cause of kidney failure in developed countries. To treat DKD more effectively, it is essential to identify new drug targets and to judge the success of such developments using reliable markers. The olink proximity extension assay (PEA) allows measuring 92 proteins across 96 samples per panel simultaneously using only 1µl of plasma. To identify novel protein biomarkers for DKD the olink PEA was selected and evaluated in this study.

Methods

Plasma from DKD patients with different CKD stages (0,2,4) (n=62,mean age 70y) as well as healthy controls (n=9,mean age 62y) were used for protein profiling with the olink PEA. Plasma was obtained from informed and consenting donors. Here, two antibodies labeled with unique, partially complementary oligonucleotides bind pair-wise to the target protein. The formed double-stranded sequence is detected and quantified using RT-PCR. Relevant proteins were verified with ELISA for evaluation of the olink PEA.

Results

The CKD marker FGF23 showed higher expression in plasma of CKD4 patients (n=36,mean age 74y) than in CKD2 patients (n=20,mean age 69y) and CKD0 (n=6, mean age 61y) when measured with olink PEA. This was also seen in the FGF23 ELISA. Also markers as VCAM1 and PECAM1 had similar expression patterns in the olink PEA and ELISA measurements. Correlation analysis showed significant correlation between the 2 methods when FGF23 (p<0.001,r=0.922), VCAM1 (p<0.001,r=0.84) and PECAM1 (p<0.001,r=0.851) were compared. The olink PEA also identified other differentially expressed proteins in the observed groups. Even differences between CKD stages were detected. 48 proteins out of 192 proteins were significantly different among the groups (panel CV2 and 3). Stem cell factor (SCF) which contributes to renal fibrosis was significantly upregulated in plasma of CKD2 patients compared to CKD0 patients and even higher in CKD4 patients.

Conclusion

The olink PEA and ELISA showed similar patterns and correlated significantly for FGF23, VCAM1 and PECAM1 in plasma of DKD patients. Moreover, other proteins which were different between DKD patients with different CKD stages and control groups were identified. Therefore, the olink PEA might be a promising tool to identify novel biomarkers for possible new drug targets and treatment evaluation for DKD.