Does insulin-like growth factor-1 mediate protein-induced kidney growth in infants?: A secondary analysis from a randomized controlled trial

Abstract

Background: Animal models have shown that insulin-like growth factor I (IGF-I) may mediate protein-induced kidney growth. Our aim was to analyze the effect of IGF-I on proteininduced kidney growth in healthy infants. Methods: This is a secondary analysis of a randomized trial that compared growth of infants fed with a higher-protein (HP) (n = 169) vs. lower-protein (LP) (n = 182) formula (in the first year of life). Outcome measures were anthropometric parameters, kidney volume (cm 3 ), and total and free IGF-I (ng/ml). results: The highest levels of total and free IGF-I were found in the HP group. Both parameters correlated significantly with BMI z-score (r = 0.229, P < 0.001 and r = 0.223, P < 0.001, respectively), kidney volume (r = 0.115, P = 0.006 and r = 0.208, P < 0.001, respectively), and kidney volume/body length (r = 0.109, P = 0.010 and r = 0.194, P < 0.001, respectively) at 6 mo. Linear regression analyses showed a significant effect of free IGF-I on kidney volume in models, including significant effects of HP formula and anthropometry. The structural equation model revealed a significant direct effect of the HP formula on kidney volume and an indirect effect mediated by free IGF-I. conclusion: This study suggests that IGF-I partly mediates protein-induced kidney growth in healthy infants. IGF-I could be involved in a pathway for the programming of the renal system. r ecent research on the early origins of adult diseases has highlighted the importance of nutrition early in life. Early nutrition could affect body structures and tissue development, which could be expressed as a permanent effect on a function that could affect health in adulthood (1). This is what is known as nutritional programming. Nutritional factors could act in different tissues and systems during a critical period of development affecting growth (2). Programming through early growth mechanisms may affect different body tissues and organs, such as bone, muscle, adipose tissue, the heart, and the kidney. Different nutritional interventions early in life have been shown to produce permanent effects on kidney function and structure. For instance, it has been proposed that poor nutritional status during gestation may affect nephrogenesis in the offspring, which could lead to impaired kidney development that could induce hypertension risk as well as poor kidney function in adulthood (3,4). Conversely, increased protein supply has been reported to stimulate kidney growth not only prenatally but also in postnatal life, both in animal models (5) and in humans (6). One of the mechanisms that may induce compensatory kidney growth in response to an increase in protein supply is the increased renal workload in response to urea and other compounds derived from protein metabolism (7,8). Furthermore, animal models have shown that insulin-like growth factor I (IGF-I) may also mediate proteininduced kidney growth. However, there is little evidence suggesting a direct effect of IGF-I on kidney size or function in humans. The relationship between IGF...

Higher protein intake increases cardiac function parameters in healthy children: metabolic programming by infant nutrition—secondary analysis from a clinical trial

“…These findings in adults were also observed in younger patients as well as in animal models (14)(15)(16). Recently, we found that nonextremely variations in protein supply with infant formulae resulted in varying kidney growth and function in healthy infants, and this was partly mediated by modulation of the IGF-1 axis (3,7).…”

“…This mechanism is partly responsible for the protein-induced increase in anthropometric parameters, as well as in some internal organs such as the kidney in healthy children (7,29). Protein intake induces IGF-1 secretion which, in turn, induces an increase in weight through its anabolic and metabolic effects in most cell lines (30,31).…”

“…This influence can be exerted by a direct effect on the target organs (5) and via the modulation of whole body size (6) resulting in functional load of vital organs. Recent evidence indicates that feeding infant formulas with higher protein (HP) content resulted in an increased kidney volume, with a direct effect on kidney function, and an increase in whole body mass (3,7). One of the target organs affected by early protein intakes is the heart, the development of which occurs in an early embryonic phase.…”

“…However, proteins can also affect the growth of the heart through a systemic stimulation of the constituents of the insulin-like growth factor 1 (IGF-1) axis. The rationale in suggesting this mechanism is based on the observation that increased protein intakes, via infant formula diets, under nonextreme conditions, stimulate the growth of other organs, such as the kidney (7). Further, cardiac hypertrophy in acromegaly is partly mediated by the growth hormone (GH)/IGF-1 axis; a meta-analysis confirmed that treating acromegaly with IGF-1 analogues (aiming to reduce the growth hormone/IGF-1 axis activity) reduces the cardiac hypertrophy and improves hemodynamic parameters (13).…”

Protein intake and nutritional programming: metabolic consequences

“…Moreover, IGF-I concentrations have been associated with weight gain in the first 6 months of life [7]. Additionally IGF-I could partly mediate protein-induced kidney growth in healthy children [8]. This phenomenon was observed in the HP group: children at 6 months of life showed a significantly greater kidney volume compared with the LP group [9].…”