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Kidney Week

ASN / Education & Meetings / Kidney Week /
Abstract: TH-PO451

Increased Urinary Ferritin in Patients with Autosomal Dominant Polycystic Kidney Disease

Session Information

Category: Genetic Diseases of the Kidneys

  • 1201 Genetic Diseases of the Kidneys: Cystic

Authors

  • Sharma, Madhulika, The University of Kansas School of Medicine, Kansas City, Kansas, United States
  • Sommer, Nicole, The University of Kansas School of Medicine, Kansas City, Kansas, United States
  • Kavanaugh, Matthew A., The University of Kansas School of Medicine, Kansas City, Kansas, United States
  • Tran, Pamela Vivian, The University of Kansas School of Medicine, Kansas City, Kansas, United States
  • Yu, Alan S.L., The University of Kansas School of Medicine, Kansas City, Kansas, United States
  • Wallace, Darren P., The University of Kansas School of Medicine, Kansas City, Kansas, United States
Background

Polycystic kidney disease (PKD) is the fourth leading cause of renal failure among adults, yet
reliable blood or urine diagnostic and prognostic biomarkers are lacking. Diagnosis is usually made by ultrasound or MRI scanning to estimate height adjusted total kidney volume (htTKV) or PKD mutation analysis, which are expensive. We previously showed that ferritin accumulates in the cystic epithelial cells of PKD kidneys due to loss of ferritinophagy. Here, we evaluate the potential of ferritin as a biomarker of ADPKD progression.

Methods

Cystic fluid from ADPKD patients, urines and urinary extracellular vesicles (UEVs) from normal and ADPKD patients, primary cultures of cyst epithelial cells from ADPKD kidneys and tubule epithelial cells from normal human kidneys (NHK) were obtained from age matched individuals with the assistance of the Kansas Clinical Research Core and Biomaterials and Biospecimens Core at the Kansas PKD Center. ADPKD and NHK cells were grown in low serum, and conditioned media were obtained for the measurement of ferritin by Western blot analysis. Cystic fluid, urine, UEVs and conditioned media were evaluated for ferritin expression via Western blots and ELISA. Urine from normal and PKD (Pkd RC/RC/Pkd2+/-) mice was also assessed for ferritin expression.

Results

Ferritin was detected as monomer, dimer, and tetramer units in the cystic fluid of ADPKD patients. Of the urine samples tested, ferritin was detected in one ADPKD patient, and it was not detected in any of the normal individuals. Conditioned media from ADPKD cells had 5 times higher ferritin compared to media from NHK cells. UEVs from ADPKD patients also had significantly more ferritin compared to UEVs from normal age matched individuals. These ferritin levels in UEVs appeared to correlate partially with the Mayo Imaging Classification categories. Moreover, we found that ADPKD mice had increased urinary ferritin compared to WT mice.

Conclusion

Ferritin, secreted by cyst epithelial cells, accumulates in cystic fluid and urine of ADPKD patients and appears to correlate with disease progression. Further studies will test the potential role of ferritin as a diagnostic, prognostic, and a response biomarker for ADPKD.

Funding

  • Other U.S. Government Support