open access publication

Article, Early Access, 2024

Insulin-like growth factor-1 effects on kidney development in preterm piglets

PEDIATRIC RESEARCH, ISSN 0031-3998, 0031-3998, 10.1038/s41390-024-03222-3

Contributors

Zhong, Jingren [1] Doughty, Richard [2] Thymann, Thomas 0000-0001-7480-6064 [1] Sangild, Per Torp [1] [3] [4] [5] Nguyen, Duc Ninh 0000-0002-4997-555X [1] Muk, Tik (Corresponding author) [1]

Affiliations

  1. [1] Univ Copenhagen, Dept Vet & Anim Sci, Sect Comparat Paediat & Nutr, Frederiksberg, Denmark
  2. [NORA names: KU University of Copenhagen; University; Denmark; Europe, EU; Nordic; OECD];
  3. [2] Akershus Univ Hosp, Dept Pathol, Lorenskog, Norway
  4. [NORA names: Norway; Europe, Non-EU; Nordic; OECD];
  5. [3] Odense Univ Hosp, Dept Pediat, Odense, Denmark
  6. [NORA names: Region of Southern Denmark; Hospital; Denmark; Europe, EU; Nordic; OECD];
  7. [4] Rigshospitalet, Dept Neonatol, Copenhagen, Denmark
  8. [NORA names: Capital Region of Denmark; Hospital; Denmark; Europe, EU; Nordic; OECD];
  9. [5] Odense Univ Hosp, Dept Pediat, Odense, Denmark
  10. [NORA names: SDU University of Southern Denmark; University; Denmark; Europe, EU; Nordic; OECD]

Abstract

Background Preterm birth disrupts fetal kidney development, potentially leading to postnatal acute kidney injury. Preterm infants are deficient in insulin-like growth factor 1 (IGF-1), a growth factor that stimulates organ development. By utilizing a preterm pig model, this study investigated whether IGF-1 supplementation enhances preterm kidney maturation.Methods Cesarean-delivered preterm pigs were treated systemically IGF-1 or vehicle control for 5, 9 or 19 days after birth. Blood, urine, and kidney tissue were collected for biochemical, histological and gene expression analyses. Age-matched term-born pigs were sacrificed at similar postnatal ages and served as the reference group.Results Compared with term pigs, preterm pigs exhibited impaired kidney maturation, as indicated by analyses of renal morphology, histopathology, and inflammatory and injury markers. Supplementation with IGF-1 reduced signs of kidney immaturity, particularly in the first week of life, as indicated by improved morphology, upregulated expression of key developmental genes, reduced severity and incidence of microscopic lesions, and decreased levels of inflammatory and injury markers. No association was seen between the symptoms of necrotizing enterocolitis and kidney defects.Conclusion Preterm birth in pigs impairs kidney maturation and exogenous IGF-1 treatment partially reverses this impairment. Early IGF-1 supplementation could support the development of preterm kidneys.Impact Preterm birth may disrupt kidney development in newborns, potentially leading to morphological changes, injury, and inflammation. Preterm pigs have previously been used as models for preterm infants, but not for kidney development. IGF-1 supplementation promotes kidney maturation and alleviates renal impairments in the first week of life in preterm pigs. IGF-1 may hold potential as a supportive therapy for preterm infants sensitive to acute kidney injury.

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