Abstract: SA-OR067
Altered Nephron Progenitor Cell Dynamics Drive Long-Term Kidney Abnormalities Following Preterm Birth
Session Information
- Innovations in Pediatric Nephrology and Kidney Development
November 08, 2025 | Location: Room 371A, Convention Center
Abstract Time: 05:00 PM - 05:10 PM
Category: Pediatric Nephrology
- 1900 Pediatric Nephrology
Authors
- Amleh, Athar, Hadassah University Medical Center, Jerusalem, Israel
- Piran, Mehran, Monash University, Melbourne, Victoria, Australia
- Moreau, Julie Liliane, Monash University, Melbourne, Victoria, Australia
- Nechama, Morris, Hadassah University Medical Center, Jerusalem, Israel
- Combes, Alexander N., Monash University, Melbourne, Victoria, Australia
- Volovelsky, Oded, Hadassah University Medical Center, Jerusalem, Israel
Background
Preterm birth, affecting 10% of live births worldwide, is associated with lower nephron number and up to fivefold increased risk of chronic kidney disease. However, the mechanisms linking prematurity and impaired kidney development remain unclear. We investigated how preterm birth influences nephron endowment, kidney function, and progression of kidney injury in a mouse model.
Methods
A mifepristone-induced mouse model of preterm birth was established. Bulk RNA sequencing was performed on sorted nephron progenitor cells (NPCs) and non-NPCs populations from post-conception (PC) days PC19.5 to PC20.5, encompassing preterm birth and the final window of nephrogenesis. Kidney structure and function were compared between preterm and term-born mice at postnatal day (P)30 and P180. Nephron number, glomerular morphology, and kidney injury markers were assessed.
Results
Transcriptomic analysis in a preterm mouse model at PC 19.5 revealed induction of cellular stress pathways and impaired differentiation in NPCs, which resolved 24 hours later. No significant changes were recorded in non-NPC populations. NPC proliferation was increased after preterm birth without a change in apoptosis. Nephrogenesis was extended for 24 hours in mice born preterm compared to term controls. Despite these compensatory mechanisms, preterm birth resulted in 17% fewer nephrons at P30 and 25% lower kidney-to-body weight ratio at P30 and P180, despite a 40% increase in body weight by P180. Mice born preterm had elevated markers of kidney injury, including a 50% increase in serum creatinine, 35% higher NGAL, a doubling in urinary albumin, and elevated KIM1. Glomerular density was reduced by 30% in P180 mice born preterm. Glomeruli were primarily localized in the medulla, with increased Bowman's space to glomerular area ratios consistent with filtration defects.
Conclusion
Preterm birth alters NPC differentiation through an acute stress response, impairing nephron endowment and predisposing to lasting kidney injury. These findings provide mechanistic insight into nephron deficit and impaired kidney function after preterm birth and suggest potential targets to support kidney development in preterm infants.