Abstract: SA-PO359

TGF Beta Pathway Enriched as Candidate Plasma Severity Biomarkers in CKD

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 301 CKD: Risk Factors for Incidence and Progression

Authors

  • Van eyk, Jennifer E, Cedars Sinai Medical Center, Los Angeles, California, United States
  • Inker, Lesley, Tufts Medical Center, Boston, Massachusetts, United States
  • Coresh, Josef, Welch Center for Prevention, Epidemiology & Clinical Research, Baltimore, Maryland, United States
  • Kimmel, Paul L., National Institute of Diabetes and Digestive Kidney Diseases (NIDDK), Bethesda, Maryland, United States
  • Tin, Adrienne, None, Baltimore, Maryland, United States

Group or Team Name

  • Biocon 1
Background

Our hypothesis is that in-depth proteomics discovery could identify novel plasma biomarkers that could be useful for the prognosis for development of chronic kidney disease (CKD) and to monitor progression (severity) of CKD. Furthermore, that as subset of markers would be related to key signaling pathways underlying the disease.

Methods

A four group design in which 64 plasma samples collected at two time points (T0 and T1) for 16 cases and 16 controls were analyzed. Cases were individuals with GFR slope >5ml/min/year and a total decline of at least 30 ml/min/year follow-up of at least 3 years while the controls had <1 ml/min/year for at least 3 years matched by age, sex, race, diabetes, hypertension, GR at T0, ACR. Each sample was depleted of the top 14 abundant plasma proteins, fractionated using reversed phase HPLC, digested, analyzed by mass spectrometry and batched searched. Proteins were ranked based on p values for prognosis (protein differences between cases and controls at T=0) and severity (cases between T0 &T1 / controls between T0 & T1) and deteremined pathways between the various candidate markers.

Results

Across all plasma samples, 1151 nonredundant protiens were identified with a protein and peptide probability of <0.1% (with >625,000 spectral counts). There were 3 and 43 candidate prognostic markers that were found to have p<0.01 and p<0.05, respectively. Within in this top group of severity markers were APO II, APO CIII, Haptoglobin and APOL1 which were ranked 4th (p=0.0058), #6 (p=0.011),13th (p=0.018) and 19th (p=0.021), respectively for prognosis. There were 2 and 66 candidate severity markers with p<0.01 and p<0.05, respectively. Of these CRP, Cystatin C and beta trace protein were ranked 6th (p=0.004), 7th (p=0.006) and 18th (P=0.04), respectively, as severity markers. Interestingly, the TGF beta pathway proteins was enriched in the candidate severity proteins (p<0.05) based on over 15 protein linkages. Although TGF beta 1 was identified in this data set, 90% of the data was missing.

Conclusion

This study indicates that de novo proteomic analysis of plasma can confirm changes of known biomarkers and identify potential new biomarkers. That different plasma proteins are aligned with prognosis versus severity. Proteins in the TGF beta pathway are particularly enriched as candidate severity biomarkers.

Funding

  • NIDDK Support