Zhong Jingren, Doughty Richard, Thymann Thomas, Sangild Per Torp, Nguyen Duc Ninh, Muk Tik
Section for Comparative Paediatrics and Nutrition, Department of Veterinary and Animal Sciences, University of Copenhagen, Frederiksberg, Denmark.
Department of Pathology, Akershus University Hospital, Lørenskog, Norway.
Pediatr Res. 2024 Dec;96(7):1655-1665. doi: 10.1038/s41390-024-03222-3. Epub 2024 May 18.
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.
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.
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.
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.
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.
早产会干扰胎儿肾脏发育，可能导致出生后急性肾损伤。早产儿缺乏胰岛素样生长因子1（IGF-1），这是一种刺激器官发育的生长因子。本研究利用早产猪模型，调查补充IGF-1是否能促进早产肾脏成熟。
剖宫产出生的早产猪在出生后5、9或19天接受全身IGF-1或载体对照治疗。收集血液、尿液和肾脏组织进行生化、组织学和基因表达分析。年龄匹配的足月出生猪在相似的出生后年龄处死后作为参考组。
与足月猪相比，早产猪的肾脏成熟受损，这通过肾脏形态学、组织病理学以及炎症和损伤标志物分析得以体现。补充IGF-1减少了肾脏不成熟的迹象，尤其是在生命的第一周，表现为形态改善、关键发育基因表达上调、微观病变的严重程度和发生率降低以及炎症和损伤标志物水平下降。未观察到坏死性小肠结肠炎症状与肾脏缺陷之间的关联。
猪早产会损害肾脏成熟，外源性IGF-1治疗可部分逆转这种损害。早期补充IGF-1可支持早产肾脏的发育。
早产可能会干扰新生儿的肾脏发育，可能导致形态变化、损伤和炎症。早产猪此前一直被用作早产儿模型，但未用于肾脏发育研究。补充IGF-1可促进早产猪出生后第一周的肾脏成熟并减轻肾脏损伤。IGF-1可能有望作为对急性肾损伤敏感的早产儿的支持性治疗方法。
