Biomarker Portfolio

Fibrosis is a hallmark feature of HFpEF pathology, acting as a driver of outcome. Understanding the intricate pathways that lead to fibrogenesis, and how they ultimately impact pathogenesis, is important for understanding how to treat HFpEF. We have developed a biomarker of fibroblast activity, PRO-C6, which independently and with high precision can identify a subset of HFpEF patients with a very elevated risk of adverse outcome.

Endotrophin is a signaling molecule released from collagen type VI (COL VI). Endotrophin can be measured by the PRO-C6 assay, which quantifies the levels of COL VI formation.

Click here for a detailed overview on PRO-C6.

PRO-C6 and C3M in serum (sPRO-C6, sC3M) and urine (uPRO-C6, uC3M) were measured by ELISA in 663 patients with T1D ranging from normoalbuminuric to macroalbuminuric. Association of the biomarkers with mortality, CVEs, heart failure, decline in estimated glomerular filtration rate (eGFR) ≥30%, and end-stage renal disease (ESRD) were tested in Cox proportional hazards models after log2 transformation and adjusted for relevant clinical characteristics. Hazard ratios (HRs) were reported per doubling of biomarker levels. High levels of sPRO-C6 were independently associated with a higher risk of all-cause mortality (HR 2.26 [95% CI 1.31-3.87], P \u003c 0.0031). There was an association with higher risk of CVEs (n = 94) and heart failure (n = 28) but not after adjustment (P ≥ 0.58). In relation to renal outcomes, adjusted sPRO-C6 was associated with a higher risk of eGFR decline ≥30% in T1D, with eGFR \u003e45 and \u003e30 mL/min/1.73 m2, and with a higher risk of ESRD (all P ≤ 0.03). Higher uPRO-C6 was associated with a lower risk of decline in eGFR.

We examined a cohort of 49 IgAN and 47 AAV patients. A validation cohort of 85 IgAN patients was included. Endotrophin (ETP) was measured in serum (S-ETP) and urine (U-ETP/Cr) samples, taken on the same day before renal biopsy was performed, using the ELISA PRO-C6. The biopsies were evaluated for interstitial fibrosis and tubular atrophy according to the Banff and MEST-C scores. S-ETP and U-ETP/Cr levels correlated with kidney function, increased with CKD severity, correlated with the extent of interstitial fibrosis and gradually increased with increasing degree of interstitial fibrosis and tubular atrophy. ETP outperformed the known fibrosis biomarker Dickkopf-3 for discrimination of patients with high fibrotic burden. The association of S-ETP and U-ETP/Cr with the level of kidney fibrosis was confirmed in the validation cohort.

• A Fragment of Collagen Type VI alpha-3 chain is Elevated in Serum from Patients with Gastrointestinal Disorders
• Biopsy-Controlled Non-Invasive Quantification of Collagen Type VI in Kidney Transplant Recipients: A Post-Hoc Analysis of the MECANO Trial
• Endotrophin and C6Ma3, serological biomarkers of type VI collagen remodelling, reflect endoscopic and clinical disease activity in IBD
• Endotrophin is associated with chronic multimorbidity and all-cause mortality in a cohort of elderly women
• Endotrophin, a collagen type VI-derived matrikine, reflects the degree of renal fibrosis in patients with IgA nephropathy and in patients with ANCA-associated vasculitis
• Endotrophin, a Collagen VI Formation–Derived Peptide, in Heart Failure
• Endotrophin, a pro-peptide of Type VI collagen, is a biomarker of survival in cirrhotic patients with hepatocellular carcinoma
• Endotrophin, an extracellular hormone, in combination with neoepitope markers of von Willebrand factor improves prediction of mortality in the ECLIPSE COPD cohort
• Serum endotrophin identifies optimal responders to PPARγ agonists in type 2 diabetes
• Serum endotrophin, a type VI collagen cleavage product, is associated with increased mortality in chronic kidney disease
• The novel collagen matrikine, endotrophin, is associated with mortality and cardiovascular events in patients with atherosclerosis
• Type VI collagen turnover-related peptides-novel serological biomarkers of muscle mass and anabolic response to loading in young men
• Urinary endotrophin predicts disease progression in patients with chronic kidney disease