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ASN / Education & Meetings / Kidney Week /
Abstract: SA-PO318

Development of a Novel Assay to Quantify Circulating Endotrophin and Validation as a Risk Marker of Complications in Type 2 Diabetes

Session Information

Category: Diabetic Kidney Disease

  • 702 Diabetic Kidney Disease: Clinical

Authors

  • Genovese, Federica, Nordic Bioscience, Herlev, Herlev , Denmark
  • Groen, Solveig Skovlund, Nordic Bioscience, Herlev, Herlev , Denmark
  • Møller, Alexandra L., Nordic Bioscience, Herlev, Herlev , Denmark
  • Hansen, Tine, Steno Diabetes Center Copenhagen, Herlev, Capital Region of Denmark, Denmark
  • Rossing, Peter, Steno Diabetes Center Copenhagen, Herlev, Capital Region of Denmark, Denmark

Group or Team Name

  • BNPCure Study Group.
Background

Endotrophin (ETP), a bioactive fragment of type VI collagen (COL6), has been widely evaluated as a biomarker of risk of outcome in type 2 diabetes (T2D). The most used assay to quantify ETP is a competitive ELISA employing an antibody targeting the C-terminal of the α3 chain of COL6, encompassing part of the ETP sequence (nordicPRO-C6TM). We developed a sandwich ELISA targeting specifically the 77 amino acid sequence of ETP (nordicEndotrophinTM), which employes a neo-epitope specific antibody targeting the N-terminal end of ETP after cleavage, and the antibody targeting the C-terminal end of COL6A3 (PRO-C6). We evaluated the potential of the two assays as risk markers of T2D adverse outcomes.

Methods

We quantified ETP employing the nordicPRO-C6TM and the nordicEndotrophinTM assays at baseline in serum of 194 individuals with T2D and microalbuminuria from an observational study conducted at Steno Diabetes Center Copenhagen. Endpoints included cardiovascular events (CV mortality, stroke, ischemic CVD, and HF), mortality, and kidney disease progression, defined as decline in estimated glomerular filtration rate (eGFR) of more than 30%. Median follow-up time was 4.9 to 6.3 years. Adjusted Cox-proportional regression analysis was employed to evaluate the association of a 2-fold increase in the biomarkers with the specified endpoints. Adjustment included baseline age, sex, BMI, HbA1c, systolic blood pressure, LDL cholesterol, urinary albumin excretion, eGFR and current smoking.

Results

The nordicEndotrophinTM had accepted linearity, precision, and accuracy in human serum. It showed a similar performance in terms of association to outcome than nordicPRO-C6TM, potentially with a higher prognostic power for cardiovascular events than the competitive assay in this cohort (Table). The correlation between the two assay was: Spearman r=0.57, P<0.0001.

Conclusion

The nordicEndotrophinTM assay quantifies specifically the endotrophin molecule in circulation, presenting a similar, or possibly higher, prognostic power for complications of T2D than the competitive ELISA used so far to quantify ETP.

OutcomePRO-C6 HR (95% CI)pEndotrophin HR (95% CI)p
All-cause mortality (n=25)2.99 (1.60-5.62)0.00064.97 (2.11-11.70)0.0002
CV events (n=37)1.61 (0.82-3.18)0.173.51 (1.69-7.27)0.0007
CKD progression (n=40)3.22 (1.75-5.92)0.00022.42 (1.22-4.80)0.01

Funding

  • Commercial Support – Nordic Bioscience