Renal Hypoplasia or Aplasia (RHDA) describes a continuum of severe renal developmental anomalies typified by smaller than normal size kidneys (hypoplasia) or complete absence (aplasia). Protheragen focuses on thorough preclinical drug and therapy development for RHDA with an emphasis on the intricate genetic and developmental pathways of these renal disorders.
Introduction to Renal Hypoplasia or Aplasia
Renal Hypoplasia or Aplasia (RHDA) reflects either partial or complete absence of kidneys. The condition can be unilateral, where the other kidney is capable of compensatory hyperplasia, or bilateral, leading to a fatal condition without intervention. It is not accurate to consider RHDA as a singular genetic syndrome; rather, it is a phenotypic manifestation of various developmental anomalies of the kidney due to aberrations in multiple genes and pathways. The clinical consequences of this condition range from mild chronic kidney disease to end-stage kidney failure necessitating dialysis or transplantation during infancy or early childhood.
Pathogenesis of Renal Hypoplasia or Aplasia
The pathogenesis of RHDA is multifaceted and diverse due to the errors made during embryonic development of the kidney. The formation of a kidney is dependent on the complex reciprocal communication and morphogenetic interplay between the metanephric mesenchyme and the ureteric bud. Disruptions in critical processes RHDA stems from are prominent including ureteric bud outgrowth failure, branching morphogenesis problems, and differentiation and survival of nephron progenitor cells are perished. A wide array of genes regulating transcription, signaling, primary cilium function, and growth factors, and other developmental pathways may incur pathogenic variants.
Fig.1 Histological features of hypoplastic kidney medullary tissue. (Bonsib, 2020)
Therapeutic Development for Renal Hypoplasia or Aplasia
| Therapeutic Strategy |
Therapeutic Target |
Key Findings/Mechanism |
Development Stage |
| CHIR99021 (Wnt Activator) |
Wnt/β-catenin pathway |
Promotes renal progenitor self-renewal and branching |
Preclinical |
| Recombinant GDNF Therapy |
RET receptor |
Enhances ureteric bud branching and nephrogenesis |
Preclinical research |
| Kangshen Granules (TCM) |
TGF-β/Smad pathway |
Multitarget antifibrotic effects |
Phase II trial |
| Shenshuai Ning Tablets |
Oxidative stress/inflammation |
Reduces tubular apoptosis and oxidative damage |
Approved |
| Everolimus |
mTORC1 pathway |
Suppresses mTOR overactivation to delay fibrosis |
Phase II trial |
| Bupi Huazhuo Decoction (TCM) |
Immune/metabolic balance |
Improves electrolyte stability and acidosis |
Phase III trial |
| Wnt10b Gene Therapy |
Wnt10b deficiency |
AAV9-mediated Wnt10b delivery to restore β-catenin signaling |
Preclinical |
| Xentuzumab (IGF-II Antibody) |
IGF-II/IGF1R axis |
Neutralizes excess IGF-II to improve renal dysplasia |
Phase II 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 specializes in developing advanced disease models for renal hypoplasia or aplasia and offers comprehensive preclinical therapeutic development services. We focus on understanding the diverse genetic and developmental impacts that lead to RHDA.
Therapeutic Development Platform for Renal Hypoplasia or Aplasia
Protheragen combines deep expertise in kidney developmental biology and the genetics of CAKUT with advanced molecular and cellular technologies to address the multifaceted mechanisms leading to RHDA. Our team delivers tailored solutions powered by cutting-edge kidney organoid systems, 3D co-culture models, and relevant in vivo platforms.
Disease Models Development for Renal Hypoplasia or Aplasia
Protheragen offers innovative and comprehensive disease models to advance the preclinical research of renal hypoplasia or aplasia. Our platform integrates cell-based models, kidney organoids, and animal models to effectively capture the genetic and developmental disruptions that cause RHDA, supporting extensive drug discovery and mechanism-based investigations focused on renal development and regeneration.
- PAX2-KO Human Renal Progenitor Cells
- RET p.R745C Mutant HEK293T Cells
- HNF1B-Methylated RPTECs
- iPSC-Derived Nephrogenic Organoids
- Pax2flox/flox; HoxB7-Cre Mice
- RetG631S Knock-in Rats
- Sall1Δex2 Zebrafish
- Human Renal Progenitor Xenografts
- CYP3A4-Humanized RHD Mice
Protheragen provides integrated preclinical development solutions specifically designed for research in rare genetic kidney diseases like renal hypoplasia or aplasia. 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
- Acien, P., and M. Acien. "Renal Agenesis, Associated Genital Malformations, and Responsible Genes." Fertil Steril 116.5 (2021): 1370-71.
- Bonsib, S. M. "Renal Hypoplasia, from Grossly Insufficient to Not Quite Enough: Consideration for Expanded Concepts Based Upon the Author's Perspective with Historical Review." Adv Anat Pathol 27.5 (2020): 311-30.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
