Kidney Week

Abstract: FR-PO457

Remote Candidate Prognostic Biomarkers of CKD among People with Type 1 Diabetes Mellitus (T1DM)

Session Information

• CKD: Risk Factors for Incidence and Progression - II
  November 03, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Chronic Kidney Disease (Non-Dialysis)

• 301 CKD: Risk Factors for Incidence and Progression

Authors

• Cai, Jian, University of Louisville School of Medicine, Louisville, Kentucky, United States

Jian Cai,

• Merchant, Michael, University of Louisville School of Medicine, Louisville, Kentucky, United States

Michael Merchant,

• Gaweda, Adam E., University of Louisville School of Medicine, Louisville, Kentucky, United States

Adam E. Gaweda,

• Brier, Michael E., University of Louisville School of Medicine, Louisville, Kentucky, United States

Michael E. Brier,

• Rovin, Brad H., Ohio State University Wexner Medical Center , Columbus, Ohio, United States

Brad H. Rovin,

• Ye, Minghao, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Minghao Ye,

• Wysocki, Jan, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Jan Wysocki,

• Molitch, Mark E., Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Mark E. Molitch,

• Batlle, Daniel, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Daniel Batlle,

• Klein, Jon B., University of Louisville School of Medicine, Louisville, Kentucky, United States

Jon B. Klein,

Group or Team Name

• For DCCT/EDIC study and CKD Biomarkers Consortium

Background

: It has been difficult to identify biomarkers that antedate the development of CKD. We used a plasma proteomic approach to evaluate samples from participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Intervention and Complications (DCCT/EDIC) with the goal to establish surrogate prognostic biomarkers of CKD in T1DM.

Methods

Samples from 23 cases (defined as participants who went on to develop CKD stage 3 (GFR<60ml/min/1.73m²) were examined prior to developing CKD. Two samples from these cases were analyzed; an early sample during DCCT and a later sample from each same subject during EDIC. 23 controls were participants in whom GFR remained well above 60ml/min/1.73m² after collection of the two matching samples during DCCT and EDIC. Samples were immunodepleted, trypsinized, labeled with 10-plex tandem mass tag (TMT), and analyzed by high resolution 2D-LCMS. The data were processed prior to Wilcoxon Rank-Sum difference testing (p-value <0.05). Candidate biomarker selection was based on fold-changes (FC, <1.5 and >1.5) to identify case/control DCCT and EDIC differences.

Results

When the sample for proteomic analysis was obtained during DCCT, cases and controls had similar age, sex, GFR, HBA1C, blood pressure, albumin excretion rate (AER) and duration of DM. During EDIC, about 15 years later, there were differences (p<0.01) in GFR (83.9 vs 101.9 ml/min/1.73m²), AER (810.5 vs 24.6mg/24h) and HbA1c (9.5 vs 8.3) between cases and controls. 1,667 identified protein groups were quantified. Cross sectional cases/control proteome differences were observed during DCCT (n=12) and EDIC (n=103) study time frames. Nine proteins were observed with >1.5FC (DCCT, n=2; EDIC, n=7), many involved in insulin signaling, inflammation, and coagulation/microvascular function. These differences in proteins were identified about 20 and 4yrs, respectively before the development of CKD.

Conclusion

In people with T1DM the plasma proteome, years prior CKD stage3, has unique proteins that are potential biomarkers of disease progression.

Funding

• NIDDK Support