Kidney Week

Abstract: TH-PO179

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

Session Information

• Diabetic Kidney Disease: Clinical - I
  November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 702 Diabetic Kidney Disease: Clinical

Authors

• Opseth Rygg, Marte, Steno Diabetes Center Copenhagen, Herlev, Denmark

Marte Opseth Rygg,

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

Alexandra L. Møller,

• Rotbain Curovic, Viktor, Steno Diabetes Center Copenhagen, Herlev, Denmark

Viktor Rotbain Curovic,

• Rasmussen, Daniel Guldager Kring, Nordic Bioscience, Herlev, Denmark

Daniel Guldager Kring Rasmussen,

• Theilade, Simone, Steno Diabetes Center Copenhagen, Herlev, Denmark

Simone Theilade,

• Tofte, Nete, Steno Diabetes Center Copenhagen, Herlev, Denmark

Nete Tofte,

• Winther, Signe Abitz, Steno Diabetes Center Copenhagen, Herlev, Denmark

Signe Abitz Winther,

• Genovese, Federica, Nordic Bioscience, Herlev, Denmark

Federica Genovese,

• Karsdal, Morten Asser, Nordic Bioscience, Herlev, Denmark

Morten Asser Karsdal,

• Hansen, Tine, Steno Diabetes Center Copenhagen, Herlev, Denmark

Tine Hansen,

• Rossing, Peter, Steno Diabetes Center Copenhagen, Herlev, Denmark

Peter Rossing,

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, HbA_1c, 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