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Kidney Week

Abstract: PO0910

Omentin 1 and Histone 1 Variants as Remote Candidate Prognostic Biomarkers of CKD Among People with Type 1 Diabetes Mellitus (T1DM)

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Merchant, Michael, University of Louisville Health Sciences Center, Louisville, Kentucky, United States
  • Cai, Jian, University of Louisville Health Sciences Center, Louisville, Kentucky, United States
  • Gaweda, Adam E., University of Louisville Health Sciences Center, Louisville, Kentucky, United States
  • Barati, Michelle T., University of Louisville Health Sciences Center, Louisville, Kentucky, United States
  • Brier, Michael E., University of Louisville Health Sciences Center, Louisville, Kentucky, United States
  • Li, Ming, University of Louisville Health Sciences Center, Louisville, Kentucky, United States
  • Ye, Minghao, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Wysocki, Jan, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Rovin, Brad H., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Molitch, Mark E., Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Batlle, Daniel, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Klein, Jon B., University of Louisville Health Sciences Center, Louisville, Kentucky, United States
Background

It has been difficult to identify biomarkers that antedate the development of CKD. In a previous study we identified omentin-1 and histone H1 (HISTH1) variants as candidate surrogate prognostic biomarkers associated with future CKD development in T1DM Diabetes Control and Complications Trial (DCCT) study participants. Work presented here extends these findings into the follow-up samples from the Epidemiology of Diabetes Interventions and Complications (EDIC) study.

Methods

Paired-serum samples from 23 controls (defined as participants with stable renal function) and 23 cases (defined as participants who went on to develop CKD stage 3 (GFR<60ml/min/1.73m2) were examined prior to and following the development of CKD. HISTH1 variant proteins were quantified using a parallel reaction monitoring (PRM) LCMS method to quantify HISTH1-variant specific peptides unique to H1.1, H1.2, H1.3, and H1.4. Omentin-1 was quantified using a commercial ELISA kit for omentin-1 (BioVendor; Asheville, NC). Protein abundance data were analyzed using Kruskal-Wallis rank sum tests with an unadjusted p-value 0.05 considered significant.

Results

HISTH1 peptides did not differentiate (p>0.05) DCCT cases and controls. HISTH1.3 was significantly increased in EDIC cases over controls. A multivariate logistic regression analyses of histone peptides identified HISTH1.4 as best able classify case or control DCCT-to-EDIC progression (p<0.05). Omentin-1 quantification confirmed discovery findings (DCC control >case, fold-change 1.2, p<0.05). Additionally, in cases, omentin-1 increased significantly (p<0.0001) from the DCCT to the EDIC (1.4) whereas it did not (p=0.06) in controls (fold-change 1.1).

Conclusion

Plasma HISTH1 variants levels did not predict future CKD3 status but did predict DCCT versus EDIC cohorts. Increased plasma omentin-1 levels in DCCT cohort were associated with stable renal function but in EDIC cohort were associated with CKD stage 3. These data suggest a role for omentin-1 or pathways regulating omentin-1 expression are associated with progression of kidney function loss in T1DM.

Funding

  • NIDDK Support