Glomerular developmental delay and proteinuria in the preterm neonatal rabbit

PLoS One. 2020 Nov 9;15(11):e0241384. doi: 10.1371/journal.pone.0241384. eCollection 2020.

Abstract

Recent advances in neonatal care have improved the survival rate of those born premature. But prenatal conditions, premature birth and clinical interventions can lead to transient and permanent problems in these fragile patients. Premature birth (<36 gestational weeks) occurs during critical renal development and maturation. Some consequences have been observed but the exact pathophysiology is still not entirely known. This experimental animal study aims to investigate the effect of premature birth on postnatal nephrogenesis in premature neonatal rabbits compared to term rabbits of the same corrected age. We analyzed renal morphology, glomerular maturity and functional parameters (proteinuria and protein/creatinine ratio) in three cohorts of rabbit pups: preterm (G28), preterm at day 7 of life (G28+7) and term at day 4 of life (G31+4). We found no significant differences in kidney volume and weight, and relative kidney volume between the cohorts. Nephrogenic zone width increased significantly over time when comparing G31 + 4 to G28. The renal corpuscle surface area, in the inner cortex and outer cortex, tended to decrease significantly after birth in both preterm and term groups. With regard to glomerular maturity, we found that the kidneys in the preterm cohorts were still in an immature state (presence of vesicles and capillary loop stage). Importantly, significant differences in proteinuria and protein/creatinine ratio were found. G28 + 7 showed increased proteinuria (p = 0.019) and an increased protein/creatinine ratio (p = 0.023) in comparison to G31 +4. In conclusion, these results suggest that the preterm rabbit kidney tends to linger in the immature glomerular stages and shows signs of a reduced renal functionality compared to the kidney born at term, which could in time lead to short- and long-term health consequences.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Disease Models, Animal
  • Female
  • Kidney Glomerulus / growth & development*
  • Kidney Glomerulus / pathology*
  • Kidney Glomerulus / physiopathology
  • Pregnancy
  • Premature Birth / pathology*
  • Premature Birth / physiopathology
  • Proteinuria / pathology*
  • Proteinuria / physiopathology
  • Rabbits
  • Survival Analysis

Grants and funding

AG is funded with support of the Erasmus+ Programme of the European Union (Framework Agreement number: 2013-0040). JD is funded by The Research Foundation – Flanders (FWO Flanders) as clinical researcher (1.801207). EL is funded by The Research Foundation – Flanders (FWO Flanders) as clinical investigator (1801110N). This study was supported by The Research Foundation – Flanders (FWO Flanders) (grant G0C4419N) and Katholieke Universiteit Leuven (C2 grant: C24/18/101). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.