Developmental Programming of Hypertension and Kidney Disease

Section of Neonatology, Department of Pediatrics, Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
International Journal of Nephrology 11/2012; 2012(4):760580. DOI: 10.1155/2012/760580
Source: PubMed


A growing body of evidence supports the concept that changes in the intrauterine milieu during "sensitive" periods of embryonic development or in infant diet after birth affect the developing individual, resulting in general health alterations later in life. This phenomenon is referred to as "developmental programming" or "developmental origins of health and disease." The risk of developing late-onset diseases such as hypertension, chronic kidney disease (CKD), obesity or type 2 diabetes is increased in infants born prematurely at <37 weeks of gestation or in low birth weight (LBW) infants weighing <2,500 g at birth. Both genetic and environmental events contribute to the programming of subsequent risks of CKD and hypertension in premature or LBW individuals. A number of observations suggest that susceptibility to subsequent CKD and hypertension in premature or LBW infants is mediated, at least in part, by reduced nephron endowment. The major factors influencing in utero environment that are associated with a low final nephron number include uteroplacental insufficiency, maternal low-protein diet, hyperglycemia, vitamin A deficiency, exposure to or interruption of endogenous glucocorticoids, and ethanol exposure. This paper discusses the effect of premature birth, LBW, intrauterine milieu, and infant feeding on the development of hypertension and renal disease in later life as well as examines the role of the kidney in developmental programming of hypertension and CKD.

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    • "IUGR is associated with a several-fold increase in neonatal morbidity and mortality. In addition, evidence accumulated over the last two decades has suggested that infants with IUGR are exposed, in the long run, to a higher risk of developing chronic disease, such as obesity, hypertension , type 2 diabetes and cardiovascular disease in later, adult life (Roseboom et al. 2001; Chong and Yosypiv 2012; Luyckx et al. 2013). A recent study demonstrated that in piglets IUGR affects lipogenesis, lipid oxidation, energy supply and utilization, amino acid and protein metabolism, antioxidant ability and jejunum function after birth (He et al. 2011). "
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    ABSTRACT: The leading causes of mortality and morbidity worldwide are cardiovascular disease (high blood pressure, high cholesterol and renal disease), cancer and diabetes. It is increasingly obvious that the development of these diseases encompasses complex interactions between adult lifestyle and genetic predisposition. Maternal malnutrition can influence the fetal and early life environment and pose a risk factor for the future development of adult diseases, most likely due to impaired organogenesis in the developing offspring. This then predisposes these offspring to cardiovascular disease and renal dysfunction in adulthood. Studies in experimental animals have further illustrated the significant impact maternal diet has on offspring health. Many studies report changes in kidney structure (a reduction in the number of nephrons in the kidney) in offspring of protein-deprived dams. Although the early studies suggested that increased blood pressure was also present in offspring of protein-restricted dams, this is not a universal finding and requires clarification. Importantly, to date, the literature offers little to no understanding of when in development these changes in kidney development occur, nor are the cellular and molecular mechanisms that drive these changes well characterised. Moreover, the mechanisms linking maternal nutrition and a suboptimal renal phenotype in offspring are yet to be discerned-one potential mechanism involves epigenetics. This review will focus on recent information on potential mechanisms by which maternal nutrition (focusing on malnutrition due to protein restriction, micronutrient restriction and excessive fat intake) influences kidney development and thereby function in later life.
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    ABSTRACT: Thanks to remarkable advances in neonatal intensive care, infants who once had little chance for survival can now enter adulthood. Yet the consequences of premature birth or low birth weight (LBW) on nephrogenesis, final nephron number, and long-term kidney function are unclear. This review focuses on the theory, experimental evidence, and observational data that suggest an increased risk of chronic kidney disease (CKD) for infants born prematurely. Many premature and LBW infants begin life with an incomplete complement of immature nephrons. They are then exposed to a variety of external stressors that can hinder ongoing kidney development or cause additional nephron loss such as hemodynamic alterations, nephrotoxic medications, infections, and suboptimal nutrition. Acute kidney injury, in particular, may be a significant risk factor for the development of CKD. According to Brenner's hypothesis, patients with decreased nephron number develop hyperfiltration that results in sodium retention, hypertension, nephron loss, and CKD due to secondary focal segmental glomerulosclerosis. Because the risk of CKD in premature and LBW infants has not been accurately determined, there are no evidence-based recommendations for screening or management. Yet with the first generation of infants from the surfactant era only now reaching adulthood, it is possible that there is already an unrecognized epidemic of CKD. We suggest individualized, risk-based assessments of premature and LBW infants due to the increased risk of CKD and call for additional research into the long-term risk for CKD these infants face.
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