Kidney Week

Abstract: TH-PO1115

Type III Collagen Turnover Is Associated with Disease Progression and Mortality in CKD Patients from the Renal Impairment in Secondary Care Cohort

Session Information

• CKD: Clinical, Outcomes, Trials - I
  October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 1902 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

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

Daniel Guldager Kring Rasmussen,

• Fenton, Anthony, University Hospital Birmingham NHS Trust, Birmingham, United Kingdom

Anthony Fenton,

• Genovese, Federica, Nordic Bioscience, Herlev, Denmark

Federica Genovese,

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

Morten Asser Karsdal,

• Ferro, Charles, University Hospital Birmingham NHS Trust, Birmingham, United Kingdom

Charles Ferro,

• Jesky, Mark David, University Hospital Birmingham NHS Trust, Birmingham, United Kingdom

Mark David Jesky,

• Cockwell, Paul, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom

Paul Cockwell,

Background

Renal fibrosis is a major underlying pathological feature in patients with chronic kidney disease (CKD) and strongly predicts progression to end-stage renal disease. We hypothesized that non-invasive assessment of the development and remodeling of fibrosis may have utility for linking dynamic in situ pathology with clinical outcomes. We focused on type III collagen (COL III), one of the most abundant collagens in renal fibrosis, utilizing PRO-C3 to assess COL III formation and C3M for COL III degradation.

Methods

We measured serum (S)-PRO-C3 and S-C3M and urine (U)-PRO-C3 and U-C3M in 499 patients from the Renal Impairment In Secondary Care (RIISC) study. RIISC is a prospective, observational cohort of patients with moderate to advanced CKD. One-year disease progression was defined as a decline in eGFR >30% or commencing renal replacement therapy within 12 months. Results were adjusted for potential confounders including age, gender, pulse pressure, eGFR, and urinary albumin:creatinine ratio. Median follow-up was 46 months (range 0–72).

Results

U-PRO-C3 and S-PRO-C3 levels increased significantly with increasing CKD stage (p<0.0001), but were very weakly correlated (rho=0.1, p=0.03). Conversely, U-C3M levels decreased with increasing CKD stage (p<0.0001); there was no change in S-C3M levels with increasing CKD stage. The odds ratio (OR) for one-year disease progression for a doubling in U-C3M was 0.29 (95% CI 0.17-0.51, p<0.0001) and 0.47 (95% CI 0.23-0.96, p=0.04) in the adjusted model. Interestingly, the levels of U-C3M divided by S-C3M gave rise to a hazard ratio for development of end-stage renal disease of 0.79 (95% CI 0.63-0.99, p=0.04) in the adjusted model. S-PRO-C3 levels at baseline was able to predict mortality with hazard ratios per-doubling of S-PRO-C3 of 2.03 (95% CI 1.31-3.16, p=0.002) in the adjusted model.

Conclusion

In conclusion, we have found a dysregulated balance between COL III formation and degradation in patients with CKD, and show that this is associated with an increased risk of adverse outcomes. These findings need urgent replication in an independent cohort; if confirmed they have implications for pathotyping and therapeutic targeting in patients with CKD.

Funding

• Commercial Support – Nordic Bioscience