Kidney Week

Abstract: SA-PO317

Circulating Endotrophin Is an Early Marker of Kidney Disease Development in Persons with Type 2 Diabetes

Session Information

• Diabetic Kidney Disease: Clinical Pathology, Diagnostic and Treatment Advances
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 702 Diabetic Kidney Disease: Clinical

Authors

• Groen, Solveig Skovlund, Nordic Bioscience, Herlev, Herlev , Denmark

Solveig Skovlund Groen, MSc, PhD

• Genovese, Federica, Nordic Bioscience, Herlev, Herlev , Denmark

Federica Genovese, PhD

• Møller, Alexandra L., Nordic Bioscience, Herlev, Herlev , Denmark

Alexandra L. Møller, MS, MSc, PhD

• Thöni, Stefanie, Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, Innsbruck, Austria

Stefanie Thöni, MD

• Keller, Felix, Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, Innsbruck, Austria

Felix Keller

• Delles, Christian, School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, United Kingdom

Christian Delles, MD

• Lindhardt, Morten, University Hospital Copenhagen, Holbæk, Holbæk, Denmark

Morten Lindhardt, MD, PhD

• Hansen, Tine, Steno Diabetes Center Copenhagen, Herlev, Capital Region of Denmark, Denmark

Tine Hansen, MD

• Mayer, Gert J., Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, Innsbruck, Austria

Gert J. Mayer, MD

• Rossing, Peter, Steno Diabetes Center Copenhagen, Herlev, Capital Region of Denmark, Denmark

Peter Rossing, MD, DrMed

Background

Endotrophin (ETP), a pro-fibrotic fragment generated during collagen type VI formation, has been largely investigated as a biomarker of adverse outcome in persons with diabetic kidney disease. We investigated its potential to predict kidney disease onset in two independent type 2 diabetes (T2D) cohorts.

Methods

Levels of ETP were measured using the nordicPRO-C6^TM ELISA (Nordic Bioscience A/S) in baseline plasma from 3226 people with T2D from the Prospective Cohort Study in Patients with Type 2 Diabetes Mellitus for Validation of Biomarkers (PROVALID) and serum from 151 participants with T2D from the PRIORITY trial (NCT02040441). Participants in PRIORITY were normoalbuminuric and with normal or slightly reduced estimated glomerular filtration rate (eGFR) and 976 of the participants in PROVALID had eGFR >90 ml/min/1.73 m² at baseline. The investigated outcome was a composite kidney endpoint (sustained 40% decline in eGFR, eGFR <60 ml/min/173 m², sustained 30% increase in albuminuria with transition in albuminuria stage, kidney replacement therapy or kidney death) in PROVALID and development of microalbuminuria in at least one morning void sample in PRIORITY. Median follow-up was 4 years in both studies. Cox proportional hazards regression models and Kaplan Meyer survival analysis (for PROVALID participants with eGFR >90 ml/min/1.73 m²) were applied.

Results

A doubling of ETP was associated with a higher risk of outcome in both PROVALID, after adjustment for age, diabetes duration, HbA1c, history of atherosclerotic cardiovascular disease, systolic blood pressure (SBP), duration of hypertension, BMI, LDL- and HDL-cholesterol, and eGFR (hazard ratio (HR): 1.55, p=0.01; events: 293) and PRIORITY (HR: 1.52, p=0.036, events: 74) after adjustment for sex, age, SBP, eGFR, urinary albumin-creatinine ratio, HbA1c, and CKD273 score. Even in PROVALID participants with eGFR>90 ml/min/1.73 m² higher ETP was associated with an increased risk of experiencing the kidney endpoint (p=0.03; n = 69).

Conclusion

Circulating ETP was a risk marker for kidney outcomes in people with T2D without or with early kidney disease. This adds to the evidence that ETP is a relevant biomarker of kidney complications in T2D, even in persons with no or mild kidney disease at baseline.

Funding

• Commercial Support – Nordic Bioscience