Renal Tubular Dysgenesis (RTD) is a rare disease and a heart-breaking disorder of the kidney due to the underdevelopment of the renal tubules, and is often lethal at its most severe stages. Protheragen offers RTD specific solutions together with a complete pipeline of preclinical drug development services.
Overview of Renal Tubular Dysgenesis
Renal tubular dysgenesis (RTD) is a rare, often lethal genetic disorder marked by the partial or complete absence of proximal renal tubules, leading to oligohydramnios (severely reduced amniotic fluid) due to impaired fetal kidney function. This results in pulmonary hypoplasia from uterine compression, culminating in perinatal death or neonatal renal failure requiring intensive life-sustaining interventions.
Pathogenesis of Renal Tubular Dysgenesis
The main genetic defect of RTD is due to homozygous or compound heterozygous mutations in genes specifying the members of the renin-angiotensin system (RAS) such as AGT (angiotensinogen), REN (renin), ACE (angiotensin-converting enzyme), and AGTR1 (angiotensin II type 1 receptor). Defects of any of these genes results in some degree of deficiency or disruption of angiotensin II signaling. Angiotensin II is critical to normal fetal development of kidneys, especially in the renal tubules' maturation, differentiation, and branching morphogenetic processes. Its absence or impaired signaling leads to characteristic features of RTD such as no well-developed renal tubules and immature glomeruli.
Fig.1 Kidney showing the presence of glomeruli and only distal tubules. (Paiva Ferreira
et al., 2025)
Therapeutics Development for Renal Tubular Dysgenesis
| Therapeutic Strategy |
Therapeutic Target |
Key Findings/Mechanism |
Development Stage |
| Recombinant Human Renin (rhRenin) |
REN gene deficiency |
Exogenous renin supplementation to activate RAS system |
Preclinical |
| Belzutifan (HIF-2α Inhibitor) |
HIF-2α/hypoxia pathway |
Inhibits hypoxia-driven fibrosis (e.g., TGF-β1) |
Phase II trial |
| VEGF-C Protein Therapy |
VEGFR3/lymphangiogenesis |
Promotes peritubular angiogenesis to improve blood flow |
Preclinical |
| Everolimus (mTOR Inhibitor) |
mTORC1 pathway |
Suppresses aberrant cell proliferation and fibrosis |
Phase II trial |
| CHIR99021 (PAX2 Activator) |
Wnt/β-catenin pathway |
Enhances PAX2 expression for tubular differentiation |
Preclinical |
| PFD@LNP Nanoparticles |
TGF-β/Smad3 pathway |
Targeted antifibrotic delivery to renal interstitium |
Preclinical |
| Empagliflozin (SGLT2 Inhibitor) |
Renal tubular metabolism |
Reduces metabolic stress to slow secondary injury |
Phase III trial |
| Autologous Stem Cell Therapy |
Tubular progenitor regeneration |
iPSC-derived PAX2+ progenitors for tubular repair |
Preclinical |
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 therapeutic development for renal tubular dysgenesis. Our extensive therapeutic development services incorporate the use of sophisticated disease models that effectively capture the profound developmental features of this inherited disorder, supporting mechanism-based drug discovery for its severe renal pathology.
Therapeutic Development Platforms for Renal Tubular Dysgenesis
Disease Models Development for Renal Tubular Dysgenesis
Protheragen provides specific disease models to accelerate preclinical research on renal tubular dysgenesis. Our platform integrates cell-based models, kidney organoids, and animal models. These models are essential for studying the impact of RAS gene mutations and drug exposure on kidney development.
Cell-based & Organoid Models
- REN-KO Human Proximal Tubular Cells
- AGTR1 p.C289W Mutant HEK293 Cells
- Vascular-Tubular Co-Culture System
- Dual-Organoid (Kidney-Liver) System
Animal Models
- Ren-/- Global KO Mice
- Agtr1aflox/flox; Ksp-Cre Mice
- rtdm2/m2 Zebrafish
- ACEΔex5 Rats
- MSC-Engrafted RTD Rats
- CRRT-Supported Neonatal Piglets
Protheragen offers end-to-end preclinical development solutions specifically designed for research in severe congenital kidney disorders like renal tubular dysgenesis. We specialize in disease model development, pharmacokinetics, and drug safety evaluation, enabling us to support your investigation from the initial stages to preclinical validation.
If you are interested in our services, please don't hesitate to contact us.
References
- Paiva Ferreira, I., et al. "Renal Tubular Dysgenesis: Broadening the Discussion of the Etiological Spectrum." Cureus 17.1 (2025): e77905.
- Tseng, M. H., et al. "Autosomal Recessive Renal Tubular Dysgenesis Caused by a Founder Mutation of Angiotensinogen." Kidney Int Rep 5.11 (2020): 2042-51.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
