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Abstract: SA-PO0122

Assessing Urinary Ferritin as a Noninvasive Biomarker in ADPKD

Session Information

Category: Genetic Diseases of the Kidneys

  • 1201 Genetic Diseases of the Kidneys: Cystic (Monogenic)

Authors

  • Wang, Wei, The University of Kansas Medical Center, Kansas City, Kansas, United States
  • Singh, Siraj, The University of Kansas Medical Center, Kansas City, Kansas, United States
  • Vanamamaly, Krishi, The University of Kansas Medical Center, Kansas City, Kansas, United States
  • Placide, Sagine, The University of Kansas Medical Center, Kansas City, Kansas, United States
  • Begum, Rahima Okm, The University of Kansas Medical Center, Kansas City, Kansas, United States
  • Wallace, Darren P., The University of Kansas Medical Center, Kansas City, Kansas, United States
  • Yu, Alan S.L., The University of Kansas Medical Center, Kansas City, Kansas, United States
  • Sharma, Madhulika, The University of Kansas Medical Center, Kansas City, Kansas, United States
Background

Autosomal dominant polycystic kidney disease (ADPKD), a common inherited kidney disorder, is a leading cause of kidney failure. Although diagnosis relies on imaging and genetic testing, reliable non-invasive biomarkers for disease monitoring and risk stratification remain limited. Ferritin, an iron-storage protein, has been identified as a biomarker in luspus nephritis. We identified ferritin enrichment in ADPKD cyst fluid, cyst-lining epithelial cells, and urinary extracellular vesicles (UEVs), therefore investigated whether UEV ferritin could serve as a non-invasive biomarker for ADPKD.

Methods

Kidney tissues, primary epithelial cells, and UEVs from normal and ADPKD patients were obtained through the PKD Research Resource Consortium. UEVs from normal and ADPKD patients enrolled in the Early PKD Observational Cohort (EPOC; ages 6 months–35 years, eGFR >80 mL/min/1.73 m2) and the Consortium for Radiologic Imaging Studies of PKD (CRISP) were analyzed. Urinary ferritin was normalized to CD9. Cross-sectional and longitudinal mixed-effects models assessed associations between urinary ferritin/CD9, height-adjusted total kidney volume (htTKV), and eGFR decline. Urine from Pkd1RC/RC;Pkd2+/− mice treated with vehicle or tolvaptan was also analyzed.

Results

In the EPOC cohort, urinary ferritin/CD9 levels were significantly higher in ADPKD patients than unaffected controls (7.7 vs 3.42, P<0.001). Male sex, non-white race, and hypertension were associated with higher ferritin/CD9 levels, while no associations were observed with htTKV, Mayo Imaging Class, or eGFR after multivariable adjustment. Longitudinal analyses showed no association between urinary ferritin/CD9 and htTKV growth or eGFR decline. In the CRISP cohort concurrent TKV values were limited and excluded from analysis. Urinary ferritin/CD9 was not associated with age, sex, genotype, Mayo Imaging Class, or longitudinal eGFR decline. In PKD mouse models, urinary ferritin levels were higher than wild-type controls. Ongoing studies are evaluating ferritin as a treatment-response biomarker following tolvaptan therapy.

Conclusion

Ferritin is enriched in ADPKD cystic epithelial cells and UEVs and is elevated in ADPKD patients. Although urinary ferritin was not associated with longitudinal disease progression, these findings support urinary ferritin as a potential non-invasive biomarker for ADPKD diagnosis and disease characterization.

Funding

  • Other U.S. Government Support