Kidney Week 2025 Annual Meeting-Prenatal and Postnatal Effects on the Kidneys: Mechanisms and Innovative Therapies

Video Transcription

Video Summary

The session “Prenatal and Postnatal Effects on the Kidneys” highlighted how early-life exposures shape lifelong kidney health and potential therapies.<br /><br />Dr. Jacqueline Ho reviewed kidney development and showed that maternal diabetes can subtly impair nephron formation beyond overt congenital anomalies. In a type 1 diabetic (Akita) mouse pregnancy model, diabetes-exposed offspring had ~25% fewer nephrons. Kidneys showed increased nephron progenitor markers but fewer early nephron structures, suggesting inefficient mesenchymal-to-epithelial transition, potentially mediated by reduced miR-200 and increased ZEB1/2. Single-cell RNA-seq revealed widespread gene-expression changes, especially in distal tubule pathways (mitochondria, lipid metabolism, ion transport), including upregulated CYP4A10 and ATP6V1B1. Functionally, exposed mice showed salt-sensitive vascular/blood pressure changes and greater susceptibility to ischemia-reperfusion injury. Genome-wide methylation differences suggested epigenetic programming.<br /><br />Dr. Jennifer Charlton focused on preterm birth, when nephrogenesis is incomplete. Human and animal data indicate nephron formation may continue after preterm delivery but stops earlier and can yield abnormal glomeruli. A preterm mouse model showed earlier cessation of nephrogenesis and transcriptomic signals implicating vitamin D metabolism and impaired angiogenesis, with later immune activation. Preterm birth also increases later risks (hypertension, diabetes), and a “two-hit” model (prematurity plus diabetes) worsened podocyte loss and glomerular injury. She emphasized identifying high-risk NICU infants for kidney follow-up and exploring nutritional interventions (vitamin A, optimized sodium).<br /><br />Dr. Karen Young linked adverse perinatal exposures (e.g., hyperoxia, inflammation, preeclampsia) to accelerated kidney and lung aging via senescence and extracellular vesicles. Hyperoxia reduced renal klotho, and klotho supplementation mitigated kidney injury and improved pulmonary vascular outcomes in rodents. Mesenchymal stromal cell–derived vesicles were presented as another anti-senescence strategy.<br /><br />Dr. Heidi Steflik discussed “precision medicine” for neonatal AKI, emphasizing limits of creatinine and emerging tools: biomarkers (e.g., NGAL phenotypes), omics, renal NIRS monitoring, and AI-based risk prediction/clinical decision support, though neonatal-specific validation remains a key gap.

Asset Subtitle

Moderator(s): Samir El-Dahr, Indra Gupta

Presentation(s):

Effects of Prenatal Exposures on Postnatal Kidney Health - Jacqueline Ho
Effects of Preterm Birth on Risk for Later Kidney Diseases: Mechanisms and Targets for Intervention - Jennifer Charlton
Effects of Adverse Perinatal Exposures on Kidney Aging - Karen Young
Precision Medicine: What Will the Future Bring for Improving Neonatal Kidney Health? - Heidi Steflik

Meta Tag

Date 11/8/2025

Pathway 1 Pediatric Nephrology

Pathway 2 AKI and Critical Care

Session ID 507342

Keywords

prenatal kidney development

postnatal kidney outcomes

maternal diabetes exposure

nephron endowment reduction

mesenchymal-to-epithelial transition

miR-200

ZEB1 ZEB2

single-cell RNA sequencing

distal tubule metabolism pathways

epigenetic programming DNA methylation

preterm birth nephrogenesis

abnormal glomerulogenesis

vitamin D metabolism

two-hit model prematurity and diabetes

neonatal acute kidney injury precision medicine