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Abstract: PO0739

Human Kidney Proteomics Identifies Biomarkers Associated with Kidney Function in Patients with Diabetic Kidney Disease

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Abedini, Amin, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Moon, Salina, Joslin Diabetes Center, Boston, Massachusetts, United States
  • Niewczas, Monika A., Joslin Diabetes Center, Boston, Massachusetts, United States
  • Susztak, Katalin, University of Pennsylvania, Philadelphia, Pennsylvania, United States
Background

Diabetic kidney disease (DKD) is the most common cause of chronic kidney disease (CKD) and end stage kidney disease, worldwide. However, the pathogenesis of DKD is poorly understood. While RNA sequencing emerged as an important tool to understand gene expression changes, protein level changes are poorly understood. SOMAscan is an emerging method that can robustly measure the level of thousands of proteins.

Methods

We have performed unbiased SOMAscan proteomics and quantified the amount of 1317 proteins in 24 snap frozen kidney tissues collected from nephrectomies. Our samples included 10 control healthy samples, 10 from subjects with overt DKD (CKD stage 3a), and 14 from subjects with late DKD (CKD stages 3b or 4). Demographic and clinical characteristics of the subjects were collected.

Results

The mean of age was 61 ± 16 and 65 % of the subjects were male. The median glomerular filtration rate (eGFR) was 108 (33) in control, 54 (5) in overt DKD, and 32 (28) in late DKD. We identified 279 proteins showing differences at overt DKD samples, and 381 proteins in late DKD samples compared to controls. Gene ontology analysis indicated enrichment for immune system and metabolic processes. The protein level of matrix metalloproteinase-7 (MMP-7) showed the strongest differences between control and DKD. Linear regression, adjusted for key co-variates identified 96 proteins those levels correlated with eGFR including cystatins C and MMP-7. We observed a moderate correlation between transcript and protein levels (r = 0.43, p < 2.2e-16).

Conclusion

SOMAscan proteomics identified important changes in protein expression in overt and late DKD, these could serve as important biomarkers or therapeutic targets.

Funding

  • NIDDK Support