Altered Nephron Progenitor Cell Dynamics Drive Long-Term Kidney Abnormalities Following Preterm Birth in Mice.

Injury biomarkers were elevated at P30 and P180, with serum creatinine increased by ~50%, NGAL by ~35%, urinary albumin excretion approximately doubled (p < 0.001), and KIM-1 elevated in preterm versus term controls. Glomerular density at P180 was reduced by ~30% in preterm mice; glomeruli were disproportionately localized in the medulla, and increased Bowman’s space area and capsule ratios suggested filtration defects.

Transcriptomic profiling around the time of preterm birth revealed acute induction of cellular stress pathways and transiently impaired NPC differentiation that resolved within 24 hours. Concomitantly, we observed a short-lived increase in NPC proliferation and an approximate 24-hour extension of nephrogenesis, consistent with a compensatory response to bolster nephron formation and indicating a potential therapeutic window.

In summary, preterm birth perturbs NPC developmental timing and stress responses, leading to reduced nephron endowment and persistent susceptibility to kidney injury.