Insulin-like Growth Factor-1 Supplementation Promotes Kidney Development and Alleviate Renal Inflammation in Preterm Pigs

BackgroundPreterm birth and its associated complications cause disruption of normal prenatal renal development, leading to postnatal kidney injury and failure. Preterm infants are deficient in insulin-like growth factor 1 (IGF-1), a critical growth factor that stimulates tissue perfusion and development. Using necrotizing enterocolitis-sensitive preterm pigs as a model for preterm infants, we investigated whether IGF-1 supplementation during early life could improve kidney development and health. MethodsCaesarean-delivered preterm pigs were allocated into two groups, either consistently receiving vehicle or IGF-1 immediately after birth for 5, 9 or 19 days. Postnatal age-matched term pigs were selected and served as term control on postnatal day (PND) 5, 9, and 19. Blood, urine and kidney tissue were collected for biochemical, histological and gene expression analyses. ResultsPreterm pigs showed impaired kidney development and increased kidney insults, as indicated by reduced average glomerular area, increased abnormal glomeruli percentage and increased markers of renal injury and inflammation compared to term pigs. IGF-1 supplementation significantly reduced the abnormal glomeruli percentage, renal injury and inflammation related markers, and up-regulated certain maturation-related genes on PND5. ConclusionIGF-1 supplementation supports kidney maturation and restoration of kidney insults after preterm birth in the early life of newborns. ImpactO_LIPreterm birth disrupts kidney development in preterm pigs. C_LIO_LIPreterm birth leads to kidney injury and inflammation in preterm pigs. C_LIO_LIIGF-1 supplementation might promote kidney maturation and alleviate preterm birth associated kidney injury and inflammation in preterm pigs. C_LI