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Kidney Week

Abstract: PO1228

Biomarkers Reflecting Extracellular Matrix Turnover Are Prognostic for Kidney Function Decline in Patients with ADPKD

Session Information

Category: Genetic Diseases of the Kidneys

  • 1001 Genetic Diseases of the Kidneys: Cystic

Authors

  • Genovese, Federica, Nordic Bioscience, Herlev, Herlev , Denmark
  • Heida, Judith E., Dept. Nephrology, University Medical Center Groningen, Groningen, Netherlands
  • Sparding, Nadja, Nordic Bioscience, Herlev, Denmark
  • Karsdal, Morten Asser, Nordic Bioscience, Herlev, Herlev , Denmark
  • Gansevoort, Ron T., Dept. Nephrology, University Medical Center Groningen, Groningen, Netherlands
  • Rasmussen, Daniel Guldager Kring, Nordic Bioscience, Herlev, Herlev , Denmark
Background

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited disorders in humans and is caused by mutations in the PKD1 and PKD2 genes. The disease is characterized by development and growth of cysts leading to loss of kidney function. Fibrosis is a driving force in progression to end-stage kidney disease in ADPKD and is characterized by an imbalanced turnover of extracellular matrix (ECM). Here, we investigated the association of ECM biomarkers with rate of kidney function decline in patients with ADPKD.

Methods

We measured four markers of ECM turnover in serum and urine from 305 patients with ADPKD from the DIPAK-1 study (NCT01616927): three markers of interstitial collagen turnover (C3M, PRO-C3 and PRO-C6) and one laminin degradation marker reflecting basement membrane turnover (LG1M). The association of the biomarkers with kidney function decline was investigated with a linear mixed model (change in eGFR/year) and logistic regression (decline in eGFR of >30%). Data was log-transformed if appropriate.

Results

All four markers of kidney fibrosis in serum were associated with eGFR at baseline when adjusting for sex, age, height adjusted total kidney volume (htTKV) and PKD mutation in serum (C3M, P<0.05; PRO-C3, P<0.001; PRO-C6, P<0.001; LG1M, P<0.001). In urine, only C3M and PRO-C6 (C3M, P<0.001; PRO-C6, P<0.01) and not PRO-C3 and LG1M (PRO-C3, P=0.07; LG1M, P=0.31) were independently associated with eGFR. Serum C3M (P=0.005) as well as urinary PRO-C3 (P=0.001) and PRO-C6 (P<0.001) were associated with the rate of eGFR decline per year when adjusting for age, sex, baseline eGFR, htTKV and PKD mutation. A total of 60 patients had a decline in eGFR of >30% and when adjusting for sex, age, baseline eGFR htTKV and PKD mutation, only serum C3M (OR=1.48, P=0.02) was independently associated with a decline in eGFR of more than 30%.

Conclusion

Serum C3M as well as urinary PRO-C3 and PRO-C6 were associated with the rate of kidney function decline when adjusting for known determinants of disease severity. Also, serum C3M could identify fast progressors (decline in eGFR of >30%). These markers hold promise that components from the ECM may be used as prognostic markers in ADPKD, but should be validated first in an independent ADPKD cohort.