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Abstract: TH-PO910

Levels of Biomarkers of Extracellular Matrix Turnover in Serum and Urine Reflect the Burden of Fibrosis in Kidney Biopsies from IgA Nephropathy and ANCA-Associated Vasculitis Patients

Session Information

Category: CKD (Non-Dialysis)

  • 1903 CKD (Non-Dialysis): Mechanisms

Authors

  • Genovese, Federica, Nordic Bioscience, Herlev, Denmark
  • Sparding, Nadja, Nordic Bioscience, Herlev, Denmark
  • Karsdal, Morten Asser, Nordic Bioscience, Herlev, Denmark
  • Frausova, Doubravka, Department of Nephrology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic, Prague, Czechia
  • Honsova, Eva, IKEM, Prague, Czechia
  • Tesar, Vladimir, General University Hospital in Prague, Prague, Prague, Czechia
  • Hruskova, Zdenka, Department of Nephrology,General University Hospital and First Faculty of Medicine, Charles University, Prague 2, Czechia
Background

Renal fibrosis is a common feature of chronic kidney disease (CKD) and is characterized by an imbalanced turnover of extracellular matrix (ECM) components. It is associated with progression to end-stage renal disease, the need for dialysis or renal transplantation and with mortality. ECM biomarkers describing the morphological changes in the kidney tissue are potentially detectable in serum and urine before markers of loss of kidney function, such as serum creatinine, due to the fact that changes in the tissue precede and are the cause of changes in function.

Methods

The cohort consisted of 49 and 47 patients with IgA nephropathy (IgAN) and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), respectively. We measured a fragment of collagen type III degradation generated by MMP-9 (C3M) and a fragment of type VI collagen formation, the C5 domain of the α3 chain (PRO-C6), in paired serum and urine samples using novel ELISAs. Renal biopsies were taken at the time of sample collection. Interstitial fibrosis was quantified according to the Banff classification, and in addition, scored according to the MEST-C classification (IgAN) or classified based on AAV morphology (AAV).

Results

Urinary C3M inversely correlated (r=-0.43, p<0.0001) and PRO-C6 (in urine and serum) correlated (r=0.51, p<0.0001 and r=0.35, p=0.0009, respectively) with the level of histological fibrosis in the kidney. Whereas urinary C3M decreased, PRO-C6 increased with CKD stages and Banff scores in both patients with IgAN and AAV. In IgAN patients, urinary C3M and PRO-C6 (in urine and serum) gradually decreased and increased, respectively, with interstitial fibrosis/tubular atrophy according to MEST-C. In addition, all three ECM markers were able to separate the AAV patients with biopsies classified as sclerotic from patients with biopsies classified as focal.

Conclusion

In this study, we demonstrated that C3M and PRO-C6, novel biomarkers of ECM turnover, not only correlated with decline in kidney function, but actually reflect the burden of fibrosis in the kidneys, as confirmed by the association with the extent of kidney fibrosis in biopsies.