Preterm birth increases the risk of chronic kidney disease by modifying nephron progenitor cell activity

Background and Aim: The survival of premature infants has improved significantly in the last decades. However, due to incomplete embryonic development, exposure to nephrotoxins, and invasive procedures, this population is at high risk for various long-term diseases, such as chronic kidney disease. Therefore, we aimed to study the changes in nephrogenesis secondary to preterm birth.

Methods: We used a mouse model of induced preterm birth on the 18th gestational day using mifepristone, a progesterone antagonist. Nephrons were counted using acid maceration. Kidney function was evaluated using serum urea level. Nephron progenitor cells were sorted using Six2-GFP. Immunofluorescent staining of Six2 for nephron progenitors and Ki67 proliferation marker was used in preterm and term birth kidney sections.

Results: We demonstrate that premature cessation of nephrogenesis leads to low nephron number and, thereby, a higher risk of kidney disease later in life. Preterm birth modified the composition of nephron progenitor subpopulations with late Six2 depletion and a decline in proliferation and differentiation rates of nephron progenitor cells in the preterm kidney.

Conclusion: Preterm birth affects the population and proliferation and differentiation rates of nephron progenitor cells pool, thereby impairing nephrogenesis and increasing the risk of chronic kidney disease.