Abstract: FR-PO0636
Tracking Murine ADPKD Progression via Resazurin Dye-Based Tubular Function Assessment
Session Information
- Cystic Kidney Diseases: Basic and Translational Research
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases
Authors
- Thomas, Ashley, The University of Kansas Medical Center, Kansas City, Kansas, United States
- Jamadar, Abeda, The University of Kansas Medical Center, Kansas City, Kansas, United States
- Bajwa, Amandeep, The University of Tennessee Health Science Center College of Medicine, Memphis, Tennessee, United States
- Pabla, Navjot, The Ohio State University, Columbus, Ohio, United States
- Rao, Reena, The University of Kansas Medical Center, Kansas City, Kansas, United States
Background
Autosomal Dominant Polycystic Kidney Disease (ADPKD) involves progressive cyst expansion and early tubular disruption. However, compensatory glomerular filtration rate (GFR) maintenance limits the sensitivity of conventional biomarkers like serum creatinine for detecting early dysfunction. The RC/RC mouse model, carrying a clinically relevant Pkd1 gene mutation, mirrors human ADPKD, and similarly preserves estimated GFR despite increasing cystic burden. This highlights a critical need for diagnostic tools that directly assess tubular function to track disease progression and treatment response. Resazurin, a redox-sensitive dye cleared via OAT1-mediated secretion has emerged as a GFR-independent marker of nephron mass and tubular function in kidney injury models. We evaluated whether urinary excretion of resazurin-derived metabolites could serve as a non-invasive readout of tubular dysfunction in RC/RC mice
Methods
Male and female RC/RC and wild-type (WT) mice were administered resazurin (2 mg/kg) via single intravenous injection. Spot urine was collected 10 minutes post-injection for quantification of the fluorescent metabolite resorufin. Expression of Slc22a6 (encoding OAT1) was assessed in mouse kidneys by quantitative RT-PCR. Comparative expression analysis was also performed using RNA data from human ADPKD and normal kidney tissues.
Results
RC/RC mice exhibited a striking 4-5 fold reduction in urinary resorufin excretion compared to WT controls, revealing tubular dysfunction and cystogenesis under conditions of preserved eGFR. Gene expression analysis revealed significant downregulation of Slc22a6 expression in murine RC/RC and human ADPKD kidneys as compared to normal kidneys.
Conclusion
Urinary excretion of fluorescent resazurin metabolites provides a sensitive method for detecting ADPKD progression under conditions where plasma creatinine and GFR remain within normal ranges. Given that resazurin uptake is OAT1-dependent, and OAT1 is downregulated early in both murine and human ADPKD, these findings support its utility as a non-invasive, translational tool for monitoring disease progression
Funding
- NIDDK Support