Kidney Week

Abstract: TH-PO1149

Immunocompetent Murine Neuroblastoma Induces Kidney Fibrosis

Session Information

• Onconephrology: Emerging Biomarkers, Preclinical Models, Clinical Challenges, and Therapeutic Strategies
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Onconephrology

• 1600 Onconephrology

Authors

• Mayoral Andrade, Gabriel, Nationwide Children's Hospital, Columbus, Ohio, United States

Gabriel Mayoral Andrade, MD, PhD

• Vasquez Martinez, Gabriela, Nationwide Children's Hospital, Columbus, Ohio, United States

Gabriela Vasquez Martinez, PhD

• Robles-Planells, Claudia J., Nationwide Children's Hospital, Columbus, Ohio, United States

Claudia J. Robles-Planells, PhD

• Pulliam, Casey F., Nationwide Children's Hospital, Columbus, Ohio, United States

Casey F. Pulliam, PhD

• Chena-Becerra, Florencia, Nationwide Children's Hospital, Columbus, Ohio, United States

Florencia Chena-Becerra, PhD

• Zepeda-Orozco, Diana, Nationwide Children's Hospital, Columbus, Ohio, United States

Diana Zepeda-Orozco, MD, MS

Background

Neuroblastoma is the most common extracranial childhood tumor, and its treatment is frequently associated with acute and long-term kidney injury. However, the direct impact of neuroblastoma on kidney injury remains poorly understood. We investigated tumor-driven alterations in kidney function, tubular injury, and histopathology using an immunocompetent murine neuroblastoma model.

Methods

Eight-10-week-old male C57BL/6J mice were subcutaneously inoculated with NB6494D mouse neuroblastoma cells and followed for up to 42 days (D42) post-inoculation. Tumor-bearing mice (n = 9) were compared with age-matched tumor-free mice (control; n = 11). At study completion, kidney function was assessed by transdermal glomerular filtration rate (tGFR) measurements and serum Cystatin C (Cys C) levels. Kidney histopathological injury score was evaluated by a blinded pathologist in periodic acid-shift and trichrome-stained kidney sections. Injury score evaluated tubular injury, tubulointerstitial inflammation, glomerular changes, and fibrosis that were quantified on a scale of 0 to 4. Markers of tubular injury, mRNA and protein levels, including kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL), were measured in whole kidney tissue.

Results

Progressive tumor growth resulted in a mean tumor volume of 940.4 mm3 by D42 and an 81.8% survival rate in tumor-bearing mice compared to 100% in the control group. Mortality in tumor-bearing mice was exclusively related to the established tumor size endpoint (2000 mm³). There was no significant difference between tGFR in tumor-bearing mice compared to control, whereas serum Cys C levels were significantly increased in tumor-bearing mice (0.866 vs 1.077 mg/L; p = 0.015). No differences were observed in whole-kidney mRNA or protein levels of KIM-1 and NGAL between both groups. Histopathological analysis demonstrated a significant increase in kidney fibrosis in tumor-bearing mice (Score 2 vs 3, p = 0.005), in the absence of tubular injury, tubulointerstitial inflammation, or glomerular abnormalities.

Conclusion

Our findings demonstrate that the presence of neuroblastoma is sufficient to induce kidney fibrosis and increase serum Cystatin C in an immunocompetent murine model, even in the absence of tubular injury, tubulointerstitial inflammation, glomerular changes, or measured GFR.

Funding

• NIDDK Support