Kidney Week

Abstract: FR-PO0083

Novel Approaches Reveal Collagen Changes in Early-Stage ADPKD in Zebrafish and Mouse Models

Session Information

• ADPKD and Cystic Kidney Disease - 2
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

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

Authors

• Sussman, Caroline R., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States

Caroline R. Sussman, PhD

• Thao, Taison, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States

Taison Thao

• Morrison, Jaden N., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States

Jaden N. Morrison

• Holmes, Heather L., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States

Heather L. Holmes

• Addani, Mohamed Ahmed, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States

Mohamed Ahmed Addani, PhD

• Entriken, Seth M., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States

Seth M. Entriken

• Montgomery, Damon Anthony, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States

Damon Anthony Montgomery

• Obiorah, Angel Maame Afua, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States

Angel Maame Afua Obiorah

• Amin, Vibhuti, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States

Vibhuti Amin

• Webb, Kevin L., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States

Kevin L. Webb

• Anaam, Deema A., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States

Deema A. Anaam, MBBS

• Alzamareh, Diana, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States

Diana Alzamareh

• Osei, Lisa Yeguaa, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States

Lisa Yeguaa Osei, MS

• Macura, Slobodan, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States

Slobodan Macura, PhD

• Torres, Vicente E., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States

Vicente E. Torres, MD, PhD

• Kline, Timothy L., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States

Timothy L. Kline, MS, PhD

• Romero, Michael F., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States

Michael F. Romero, PhD

• Harris, Peter C., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States

Peter C. Harris, PhD

Background

ADPKD is the fourth most common cause of kidney failure with renal phenotypes including cyst formation, growth, and fibrosis secondary to cysts. Mounting evidence implicates the extracellular matrix (ECM) in the early stages of ADPKD, but collagen changes have not been quantified. The predominant collagen stains, Picrosirius red (PSR) and Masson’s trichrome, are limited to detecting fibrosis, a massive overexpression of collagen. Here we evaluated two novel approaches for quantifying collagen in early-stage ADPKD.

Methods

Heterozygous pkd2^hi4166 zebrafish, Pkd1^RC/RC mice in C57BL/6J, and end stage kidneys from PKD patients were analyzed. PSR was used to determine fibrotic area. Collagen hybridizing peptide (CHP, 3Helix) fluorescence intensity (arbitrary units, au) normalized to tissue area and percent fibrotic area were determined using ImageJ. CT-FIRE fiber detection software (LOCI; Madison, WI) detected and quantified collagen fibers from red fluorescence. Statistical analysis was done by t-test or ANOVA (GraphPad Prism). Data are indicated as mean ± SD.

Results

Zebrafish pkd2^+/- kidneys had similar TKV but lower texture correlation (indicating decreased homogeneity) by MRI than sibling WT (0.07±0.02 v 0.13±0.03, p<0.04). H&E staining showed no cysts or tubule dilation and PSR showed no change in fibrotic area. However, collagen labeling with CHP showed increased collagen v WT (32±12 v 14±11 au, p<0.04). CHP was validated using the mouse Pkd1^RC/RC model, showing increased collagen in late-stage disease versus WT (13-months, 17±7.0 v 6.0±1.1 au, p<0.002). CHP additionally detected increased collagen in early-stage disease at 3-months v WT (3.0±1.8 v 0.91±1.0 au, p<0.02) when fibrotic area was 5% of that at 13-months and not different from 3-month WT. Characterization of individual collagen fibers using CT-FIRE showed fiber distribution in late stage ADPKD in humans and mice was skewed towards narrower and wavier bins versus control. Similarly, fiber distribution was skewed towards wavier bins in early-stage disease at 3-months, although there was no difference in fiber width.

Conclusion

Collagen changes were quantified in early-stage ADPKD using novel methods validated in late-stage disease. Mechanistic insights into these changes may indicate novel treatment approaches and biomarkers of early-stage disease that can be tested using the phenotypes reported here of early-stage disease.

Funding

• NIDDK Support