Role of rh-IGF-1/IGFBP-3 in the postnatal kidney maturation of preterm pigs: Not so simple

The Insulin-Like Growth Factor system (IGFs) comprised by IGF-1 and the IGF-2 ligands, IGF-receptors (IGF-R) and several IGF binding proteins (IGFBP) is considered essential for regulating fetal and postnatal growth, the action of growth hormone, as well as the growth of intestinal, lung, bone, brain and kidney, the maintenance of the extracellular fluid (ECF) volume, the regulation of the immune system, glucose metabolism, and other key physiological functions. 1 , 2 In preterm infants, low levels of IGF-1 have been associated with the development of retinopathy of prematurity, bronchopulmonary dysplasia, necrotizing enterocolitis (NEC), intraventricular hemorrhages, and impaired neurodevelopment. 3 Therefore, clinical trials have been done in preterm infants to determine whether injections of recombinant human (rh)-IGF-1 combined with rh-IGFBP-3, which prolongs IGF-1’s half-life and regulates its tissue accessibility and activity, could ameliorate these complications. 3 This issue of Pediatric Research introduces a study by Zhong et al. showing that hr-IGF-1/IGFBP-3 given to preterm pigs delivered at 90% gestational age, promotes kidney maturation and mitigates the impact of preterm weight on kidney structure. 4 Based on these findings, the authors suggested that hr-IGF-1/IGFPB-3 could sever as a promising therapy for kidney immaturity in preterm infants. Here, we argue that the interpretation of these data is not so simple, and will discuss relevant issues that need to be considered to assess the clinical relevance of these findings for preterm infants,