High protein intake in neonatal period induces glomerular hypertrophy and sclerosis in adulthood in rats born with IUGR

Abstract

Background: Intrauterine growth restriction (IUGR) and postnatal nutrition are risk factors for cardiovascular and renal diseases in both humans and animals. The long-term renal effects of protein intake early in life remain unknown. The objective was to evaluate the effects of a neonatal feeding with high protein (HP) milk on renal functions and structure in IUGR male rats. Methods: Maternal gestational low protein diet was used to produce IUGR. At day 5, IUGR pups were gastrostomized in the "pup-in-the cup" model and received either normal protein (NP) milk or HP (+50% protein content) milk until day 21. After weaning, the animals were fed the same standard diet. Renal functions and structure were assessed at postnatal day 18 (D18) and in adult offspring. results: During the preweaning period, the postnatal weight gain between the two groups was unaffected. On D18, kidneys from HP offspring were heavier with significant glomerular hypertrophy (+40%, P < 0.05). HP diet was associated with significant proteinuria and glomerulosclerosis (+49%, P < 0.05). Glomerular number was unaltered. conclusion: Neonatal HP feeding following IUGR affects renal functions and structure at adulthood. These alterations may result from a single nephron glomerular hyperfiltration.

Perinatal Origins of Adult Disease

“…Personalized approaches to postnatal nutrition in these infants may be more efficient than a one size fits all strategy. Of note, postnatal overnutrition fol- lowing early intrauterine undernutrition (with/without extrauterine undernutrition) and growth restriction is a particularly deleterious growth pattern for later vascular, renal, and metabolic functions, as observed by our group and others in rats [2,3]. Interestingly, transient postnatal overfeeding during lactation in the absence of any prenatal nutritional alteration leads to hypertension, heart dysfunction, and metabolic disorders in adulthood [35,36].…”

“…During this period, functional and regulatory capacities of systems and organs are set for the long term through an adaptation under the influence of clues received from the early, nutritional, stressing, and chemical environment, based on developmental plasticity and programming. Early translation patterns of the genome thus design life trajectories that condition the risk for later chronic diseases such as hypertension, obesity, type 2 diabetes, and other non-communicable diseases (NCDs) in adulthood, as shown by both epidemiological and animal studies [2]. During early development, environmental stimuli determine not only short-term but also lifelong and transgenerationally heritable effects due to epigenetic imprinting [3].…”

Endothelial dysfunction in individuals born after fetal growth restriction: cardiovascular and renal consequences and preventive approaches

“…Rat models of IUGR induced by exposure to maternal LPD followed by early postnatal overnutrition during the lactation period or not according litter size reduction or increased protein intake to induce accelerated postnatal growth displayed alterations in renal structural development and a risk of chronic renal failure later in life. [165][166][167][168][169] Decreased glomerular number potentially leads to reduced filtration capacity, reduced salt and water retention and the subsequent development of HTN. Furthermore, early loss of nephron numbers/mass may result in a state of hyperfiltration in the remaining nephrons, which will lead to focal segmental glomerulosclerosis and further loss of glomeruli, thus initiating a vicious circle.…”

Effect of early postnatal nutrition on chronic kidney disease and arterial hypertension in adulthood: a narrative review

“…75,76 Boubred et al found in a male rat model of IUGR and hyperproteic postnatal feeding (13.1 g and 172 kcal v. 8.7 g and 155 kcal per 100 ml), that this condition was associated with proteinuria and glomerulosclerosis. 77 The same adverse outcomes were observed after overfeeding (by litter size reduction) alone, but not after IUGR alone. 78 In this study, early overfed animals with a normal BW had an increased number of nephrons, but decreased glomerular volume, suggesting an unchanged total glomerular filtration surface area.…”