Fibrogenesis Biomarkers and Clinical Disease Progression in ADPKD
- 1Cardiovascular & Renal Research, Nordic Bioscience, Herlev, Denmark
- 2Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Abstract
Introduction: Fibrogenesis contributes to disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD). In this exploratory study, we evaluated the association of protease-generated circulating and urinary collagen fragments (type III collagen degradation [C3M], type III collagen formation [PRO-C3], and type VI collagen formation [PRO-C6]), reflecting fibrogenesis and fibrolysis, with clinical outcomes in ADPKD.
Methods: We included 302 patients from the DIPAK-1 trial (lanreotide vs. standard treatment), with a mean baseline age of 48.9 ± 7.3 years and estimated glomerular filtration rate (eGFR) of 51.3 ± 11.5 ml/min per 1.73 m2. Kidney endpoints were eGFR slope, rapid disease progression (eGFR loss ≥3 ml/min per 1.73 m2 per year), and a composite kidney endpoint (30% eGFR loss or initiation of kidney replacement therapy). Net benefit analysis was performed to assess clinical utility.
Results: During 2.4 ± 0.4 years of follow-up, mean eGFR slope was −4.02 ± 3.64 ml/min per 1.73 m2 per year, 190 patients (62.9%) had rapid disease progression, and 87 (28.8%) reached the composite endpoint. After adjustment for sex, baseline age, baseline eGFR, Mayo imaging class (MIC), PKD pathogenic variant and treatment group, uPRO-C3/Cr and uPRO-C6/Cr were independently associated with eGFR slope, rapid disease progression, and the composite endpoint. uPRO-C3/Cr was also associated with HtTKV growth rate. Adding uPRO-C3/Cr or uPRO-C6/Cr improved prediction of rapid disease progression, increasing area under curve (AUC) from 0.78 (95% confidence interval [CI], 0.73–0.86) to 0.79 (95% CI, 0.73–0.86) and 0.80 (95% CI, 0.73–0.86), respectively. Decision curve analysis did not show a meaningful net benefit.
Conclusion: These findings demonstrate that uPRO-C3/Cr and uPRO-C6/Cr were independently associated with kidney outcomes in ADPKD, providing clinical evidence that extracellular matrix (ECM) remodeling is associated with ADPKD disease progression.
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BibTeX
@article{groen2026fibrogenesis,
title = {{Fibrogenesis Biomarkers and Clinical Disease Progression in ADPKD}},
author = {Solveig Skovlund Groen and Ron T. Gansevoort and Nadja Sparding and Judith E. Heida and Esther Meijer and Morten A. Karsdal and Peder Frederiksen and Federica Genovese and Thomas Bais},
journal = {Kidney International Reports},
year = {2026},
month = sep,
doi = {10.1016/j.ekir.2026.107102},
url = {https://doi.org/10.1016/j.ekir.2026.107102},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Fibrogenesis Biomarkers and Clinical Disease Progression in ADPKD
AU - Solveig Skovlund Groen
AU - Ron T. Gansevoort
AU - Nadja Sparding
AU - Judith E. Heida
AU - Esther Meijer
AU - Morten A. Karsdal
AU - Peder Frederiksen
AU - Federica Genovese
AU - Thomas Bais
PY - 2026
DA - 2026/09/23
JO - Kidney International Reports
DO - 10.1016/j.ekir.2026.107102
UR - https://doi.org/10.1016/j.ekir.2026.107102
AB - Introduction: Fibrogenesis contributes to disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD). In this exploratory study, we evaluated the association of protease-generated circulating and urinary collagen fragments (type III collagen degradation [C3M], type III collagen formation [PRO-C3], and type VI collagen formation [PRO-C6]), reflecting fibrogenesis and fibrolysis, with clinical outcomes in ADPKD. Methods: We included 302 patients from the DIPAK-1 trial (lanreotide vs. standard treatment), with a mean baseline age of 48.9 ± 7.3 years and estimated glomerular filtration rate (eGFR) of 51.3 ± 11.5 ml/min per 1.73 m2. Kidney endpoints were eGFR slope, rapid disease progression (eGFR loss ≥3 ml/min per 1.73 m2 per year), and a composite kidney endpoint (30% eGFR loss or initiation of kidney replacement therapy). Net benefit analysis was performed to assess clinical utility. Results: During 2.4 ± 0.4 years of follow-up, mean eGFR slope was −4.02 ± 3.64 ml/min per 1.73 m2 per year, 190 patients (62.9%) had rapid disease progression, and 87 (28.8%) reached the composite endpoint. After adjustment for sex, baseline age, baseline eGFR, Mayo imaging class (MIC), PKD pathogenic variant and treatment group, uPRO-C3/Cr and uPRO-C6/Cr were independently associated with eGFR slope, rapid disease progression, and the composite endpoint. uPRO-C3/Cr was also associated with HtTKV growth rate. Adding uPRO-C3/Cr or uPRO-C6/Cr improved prediction of rapid disease progression, increasing area under curve (AUC) from 0.78 (95% confidence interval [CI], 0.73–0.86) to 0.79 (95% CI, 0.73–0.86) and 0.80 (95% CI, 0.73–0.86), respectively. Decision curve analysis did not show a meaningful net benefit. Conclusion: These findings demonstrate that uPRO-C3/Cr and uPRO-C6/Cr were independently associated with kidney outcomes in ADPKD, providing clinical evidence that extracellular matrix (ECM) remodeling is associated with ADPKD disease progression.
SN - 2468-0249
ER -