Vesicoureteral Reflux (VUR) is an abnormal congenital vesicoureteral disorder that adversely affects the normal forward flow of urine from the bladder into the ureters and the kidneys. This leads to VUR patients undergoing recurrent UTIs and renal scarring. Protheragen has developed preclinical solutions for VUR integrating genetics, anatomy, and functions of nephro-urological disorders to formulate its multifactorial pathogenesis.
Introduction to Vesicoureteral Reflux
VUR stems from anomalies at the vesicoureteral junction (VUJ), notably from shortened intramural ureters or a nonfunctioning valve. It has a prevalence of 1 to 2 percent in the general pediatric population. VUR is further subclassified into two categories; primary (congenital) and secondary (acquired). Primary VUR is associated with mutations of ROBO2, UPK3A, and TNXB genes. If recurrent UTIs and renal scarring aren't treated, patients may develop hypertension, chronic kidney disease (CKD), or both. Timely intervention combined with diagnosis is essential in order to maximize renal function.
Pathogenesis of Vesicoureteral Reflux
The principal cause of VUR is a developmental anomaly concerning the vesicoureteral junction which represents the interface between the bladder and the ureter. This structure is normally considered to be a unidirectional valve; it permits the passage of urine from the ureters into the bladder while preventing backward flow during bladder contraction. In VUR, this valvular mechanism fails incompetently, resulting in the backward movement of urine flow. While its pathogenesis s quite intricate and, at times, multifactorial, genetic influences are paramount. Various studies have suggested different genes associated with the development of the kidney and the urinary tract, including some from the Wnt signaling pathway, PAX2 and RET.
Fig.1 CAKUT phenotypic spectrum includes kidney anomalies, ureter, and lower Urinary tract. (Mahmoud
et al., 2024)
Therapeutics Development for Vesicoureteral Reflux
| Drug/Technology |
Therapeutic Target |
Key Findings/Mechanism |
Development Stage |
| Ramipril (ACE Inhibitor) |
RAAS inhibition |
Slows reflux nephropathy progression |
Phase II trial |
| Alpha-Defensin Gene Therapy |
DEFA1A3 gene regulation |
Gene editing enhances antimicrobial peptide expression |
Preclinical |
| Non-Animal Stabilized Hyaluronic Acid (NASHA) |
Biocompatible bulking material |
Improved long-term stability and reduced granuloma risk |
Phase III clinical trial |
| Autologous Stem Cell Transplantation |
Ureteral mucosal regeneration |
Stem cell-biomaterial composite for tissue repair |
Preclinical |
| Probiotics |
Gut-urinary microbiome modulation |
Reduces pathogenic bacterial colonization |
Phase II clinical trial |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen is a comprehensive preclinical service provider dedicated to the discovery and development of novel therapeutics for Vesicoureteral Reflux. Our extensive therapeutic development services incorporate the use of sophisticated disease models that effectively capture important features of this inherited and developmental urological disorder.
Therapeutic Development Platforms for Vesicoureteral Reflux
Disease Models Development for Vesicoureteral Reflux
Protheragen offers innovative and comprehensive disease models to advance preclinical research into VUR. Our platform integrates cell-based models, kidney organoids, and animal models to effectively capture the genetic and developmental signatures of VUR and its impact on renal health.
- UPK3A-KO Urothelial Model
- TNXB-Mut Fibroblast Co-Culture System
- HGF-KO Smooth Muscle Cell Model
- UPK3A-Mutant Bladder Organoid
- Fibrosis-Prone Kidney Organoid
- PK3A cKO Mouse (Urothelium-Specific)
- TNXB-KO Rat Model
- Zebrafish pax2a Mutant Line
- HGF-iKO Mouse (Tamoxifen-Inducible)
- hUPK3A Transgenic Rabbit Model
Protheragen's integrated preclinical development solutions are specifically designed for research in complex renal and urological disorders like vesicoureteral reflux. We specialize in disease model development, pharmacokinetics, and drug safety evaluation, enabling us to support your investigation from target validation to IND-enabling studies.
Contact us today to accelerate your vesicoureteral reflux research with end-to-end solutions.
References
- Baginska-Chyzy, J., and A. Korzeniecka-Kozerska. "Urodynamic Evaluation: Is It Useful for Vesicoureteral Reflux Management?" J Clin Med 14.9 (2025).
- Mahmoud, A. H., et al. "Congenital Anomalies of the Kidney and Urinary Tract." Front Med (Lausanne) 11 (2024): 1384676. Print.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
