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Kidney Week

Abstract: TH-PO179

PRO-C3 as a Risk Marker for Kidney Disease Progression and Mortality in Type 1 Diabetes

Session Information

Category: Diabetic Kidney Disease

  • 702 Diabetic Kidney Disease: Clinical

Authors

  • Opseth Rygg, Marte, Steno Diabetes Center Copenhagen, Herlev, Denmark
  • Møller, Alexandra L., Nordic Bioscience, Herlev, Denmark
  • Rotbain Curovic, Viktor, Steno Diabetes Center Copenhagen, Herlev, Denmark
  • Rasmussen, Daniel Guldager Kring, Nordic Bioscience, Herlev, Denmark
  • Theilade, Simone, Steno Diabetes Center Copenhagen, Herlev, Denmark
  • Tofte, Nete, Steno Diabetes Center Copenhagen, Herlev, Denmark
  • Winther, Signe Abitz, Steno Diabetes Center Copenhagen, Herlev, Denmark
  • Genovese, Federica, Nordic Bioscience, Herlev, Denmark
  • Karsdal, Morten Asser, Nordic Bioscience, Herlev, Denmark
  • Hansen, Tine, Steno Diabetes Center Copenhagen, Herlev, Denmark
  • Rossing, Peter, Steno Diabetes Center Copenhagen, Herlev, Denmark
Background

Kidney fibrosis, a hallmark of diabetic kidney disease, is characterized by impaired extracellular matrix remodeling, causing excessive collagen deposition. We investigated if biomarkers of collagen type III (PRO-C3), VII (PRO-C7) and XXVIII (PRO-C28) formation, and a fragment of degraded crosslinked collagen type III (CTX-III), were related to kidney disease progression and mortality in people with type 1 diabetes (T1D).

Methods

The biomarkers were measured in serum by ELISA. Endpoints were 1) a composite kidney endpoint including ≥30% decline in estimated glomerular filtration rate (eGFR), onset of kidney failure (eGFR ≤15 ml/min/1.73m2, dialysis, or transplantation) and all-cause mortality; and 2) all-cause mortality. Associations with baseline biomarker levels were tested using Cox proportional hazard models after log2 transformation. Hazard ratios (HRs) are reported per doubling and adjusted for age, sex, HbA1c, eGFR, systolic blood pressure, body mass index, smoking, urinary albumin excretion rate, diabetes duration and treatment with a renin-angiotensin-aldosterone system inhibitor.

Results

We enrolled 667 individuals with T1D, 311 with normal (<30 mg/24h), 166 with moderately (30-299 mg/24h), and 190 with severely increased (≥300 mg/24h) urinary albumin excretion. Median follow-up was 5.2-6.2 years. Higher PRO-C3 was associated with development of the composite kidney endpoint (events: 125) and all-cause mortality (events: 58); adjusted HR: 1.51 (95% CI: 1.08-2.11, p=0.017) and 1.65 (1.05-2.61, p=0.031), respectively. Higher PRO-C7 was associated with a higher risk of the composite kidney endpoint (1.56 (1.16-2.09), p=0.003), but not after adjustment (p=0.40), and not associated with mortality. PRO-C28 and CTX-III were not associated with the endpoints (p≥0.13).

Conclusion

PRO-C3, a marker of collagen type III formation, was associated with kidney disease progression and death, highlighting PRO-C3 as a potential risk marker of severe complications in T1D.

Funding

  • Private Foundation Support