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Human Kidney Organoids to Uncover Preterm Birth-Associated Low Nephron Endowment
Bartholomeus T van den Berge1, Bart Smeets2, Michiel F Schreuder1
1Department of Pediatric Nephrology, Research Institute for Medical Innovation, Radboud University Medical Center, Nijmegen, The Netherlands.
Nephron
|May 18, 2026
Summary
Preterm birth impairs kidney development, leading to lifelong chronic kidney disease (CKD) risk. Kidney organoids and molecular interventions like retinoic acid show promise for enhancing nephron formation and mitigating CKD.
Area of Science:
- Developmental biology
- Stem cell research
- Nephrology
Background:
- Preterm birth severely impacts kidney development, reducing nephron count and increasing risks for hypertension and chronic kidney disease (CKD).
- Nephrogenesis (new nephron formation) stops around 36 weeks gestation, leaving preterm infants vulnerable to long-term kidney dysfunction.
- Studying human nephrogenesis is challenging due to its complexity and the lack of suitable experimental models.
Purpose of the Study:
- To investigate the potential of human induced pluripotent stem cell-derived kidney organoids to model human nephrogenesis and kidney injury.
- To explore molecular interventions for enhancing nephron formation and protecting against kidney damage in preterm infants.
- To assess the efficacy of retinoic acid (RA), glial-cell-line-derived neurotrophic factor (GDNF), and insulin-like growth factor 1 (IGF1) in improving kidney development.
Main Methods:
- Utilized human induced pluripotent stem cell-derived kidney organoids to replicate key aspects of in vitro nephrogenesis.
- Optimized organoid maturity through ureteric bud integration and enhanced vascularization.
- Investigated the effects of molecular interventions (RA, GDNF, IGF1) on nephron development and injury protection within organoid models.
Main Results:
- Kidney organoids successfully recapitulate critical nephrogenesis processes, including nephron differentiation and ureteric bud branching.
- Improved organoid maturity was achieved via enhanced vascularization and ureteric bud integration, creating a more in vivo-like environment.
- Molecular interventions demonstrated potential to enhance nephron endowment and offer protection against kidney injury.
Conclusions:
- Human kidney organoids offer a powerful, physiologically relevant platform for studying nephrogenesis and CKD mechanisms.
- Targeted molecular interventions, including RA, GDNF, and IGF1, present promising strategies for improving nephron endowment in preterm infants.
- Kidney organoid models are valuable tools for studying the impact of these interventions and mitigating CKD risk.
