Effects of Maternal Protein Restriction on the Kidney of the Newborn Young of Rats

Zeman, Frances J.

doi:10.1093/jn/94.2.111

Cited by 118 publications

(55 citation statements)

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“…This finding is in general agreement with results of previous studies in which maternal intake was more severely restricted and which used less reliable techniques to estimate glomerular number (33)(34)(35). The importance of using unbiased, stereologic techniques in renal research has recently come to the forefront (36).…”

Section: Discussionsupporting

confidence: 90%

Maternal Protein Restriction Suppresses the Newborn Renin-Angiotensin System and Programs Adult Hypertension in Rats

et al. 2001

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Restriction of maternal protein intake during rat pregnancy produces offspring that are hypertensive in adulthood, but the mechanisms are not well understood. Our purpose was to determine whether this adult hypertension could be programmed during development by suppression of the fetal/newborn reninangiotensin system (RAS) and a consequent reduction in nephron number. Pregnant rats were fed a normal protein (19%, NP) or low-protein (8.5%, LP) diet throughout gestation. Birth weight was reduced by 13% (p Ͻ 0.0005), and the kidney/body weight ratio was reduced in LP pups. Renal renin mRNA levels were significantly reduced in newborn LP pups; renal renin concentration and renin immunostaining were suppressed. Renal tissue angiotensin II levels were also suppressed in newborn LP (0.079 Ϯ 0.002 ng/mg, LP versus 0.146 Ϯ 0.016 ng/mg, NP, p Ͻ 0.01). Mean arterial pressure in conscious, chronically instrumented adult offspring (21 wk) was higher in LP (135 Ϯ 1 mm Hg, LP versus 126 Ϯ 1 mm Hg, NP, p Ͻ 0.00007), and GFR normalized to kidney weight was reduced in LP (p Ͻ 0.04). The number of glomeruli per kidney was lower in adult LP offspring (21,567 Ϯ 1,694, LP versus 28,917 Ϯ 2,342, NP, p Ͻ 0.03), and individual glomerular volume was higher (1.81 Ϯ 0.16 10 6 m 3 , LP versus 1.11 Ϯ 0.10 10 6 m 3 , NP, p Ͻ 0.005); the total volume of all glomeruli per kidney was not significantly different. Thus, perinatal protein restriction in the rat suppresses the newborn intrarenal RAS and leads to a reduced number of glomeruli, glomerular enlargement, and hypertension in the adult. Abbreviations RAS, renin-angiotensin system ERPF, effective renal plasma flow NP, normal protein (19%) diet LP, low-protein (8.5%) diet ANGII, angiotensin II PAH, para-amino hippurate A decade ago, Barker et al. first reported an inverse relationship between birth weight and death from cardiovascular disease in adulthood (1). Subsequently, a number of epidemiologic studies in different parts of the world have found a relationship between early growth patterns and the risk of cardiovascular disease in adulthood (2-8). Although these findings remain somewhat controversial (9), the majority of evidence indicates that even within the "normal" range of birth weights, babies that are born smaller have a higher risk of death from cardiovascular disease when they reach adulthood. This indicates that some factor or factors in the perinatal environment, probably related at least in part to maternal nutrition, can "program" the individual for increased cardiovascular risk later in life. However, the precise physiologic and molecular mechanisms by which this programming occurs are unknown.Recently, a rat model of perinatal protein restriction has been identified that has several features in common with the observations in humans, suggesting that this may be a good animal model of the human condition. In particular, offspring ABSTRACT460

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Section: Discussionsupporting

confidence: 90%

Maternal Protein Restriction Suppresses the Newborn Renin-Angiotensin System and Programs Adult Hypertension in Rats

et al. 2001

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“…They stated that the association between birth weight and arterial hypertension could refl ect a correla- 33 Various models for IUGR have demonstrated decreased nephron counts in rats. 5,6,34,35 In these animal studies, reductions in kidney weight and volume persist throughout life. 36 Seemingly, human pathological studies have found that asymmetric IUGR can exert a profound effect on kidney development.…”

Section: Discussionmentioning

confidence: 99%

“…Various experimental models for intrauterine growth retardation have demonstrated that reduced kidney weight persists throughout the animal's life, despite compensatory hypertrophy. [3][4][5][6] In humans, low BW full-term infants have lower kidney weight and lower glomerular profi le density than do infants with greater BW. 7 Although a moderate defi ciency in nephrons alone might not be expected to result in hypertension, several clinical observations and experimental studies have provided strong support for the notion that defi cient numbers of nephrons predispose towards hypertension in later life.…”

Section: Introductionmentioning

confidence: 99%

Blood pressure and kidney size in term newborns with intrauterine growth restriction

Matsuoka¹,

Shibao²,

Leone³

2007

Sao Paulo Med. J.

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CONTEXT AND OBJECTIVE: Low birth weight is associated with higher blood pressure in childhood and adulthood. The aim of this study was to investigate the influence of intrauterine growth restriction (IUGR) on newborn systolic blood pressure (SBP). DESIGN AND SETTING: Prospective comparative study at Neonatal and Intensive in Clinical Pediatrics Division, Maternity Hospital in Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo. METHODS: 35 newborns with IUGR and 35 without IUGR were compared. Healthy term newborns without malformations, with Apgar score at fifth minute > 6 were included. Birth weight, kidney weight/birth weight ratio, kidney weight (ultrasound scan), plasma renin activity (PRA) and SBP evolution were analyzed during the first month of life (on 1st, 3rd, 7th and 30th days). RESULTS: SBP evolution, kidney weight/birth weight ratio and PRA did not differ between the two groups. In newborns with IUGR, SBP presented positive correlations with birth weight (r = 0.387 p = 0.026) and BMI (r = 0.412 p = 0.017) on the 7th day of life. Positive correlations with birth weight (r = 0.440 p = 0.01) and birth length (r = 0.386 p = 0.026) were also seen on the 30th day. There was an inverse correlation on the 7th day between SBP and kidney weight/birth weight ratio (r = -0.420 p = 0.014), but this did not persist to the end of the month. CONCLUSIONS: IUGR seems not to have any influence on SBP, PRA or kidney weight among term newborns during their first month of life.

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“…Research has suggested that maternal malnutrition (Zeman, 1968), maternal hyperglycemia (Amri, Freund, Vilar, Merlet-Benichou, & Lelievre-Pegorier, 1999), drug exposure (Nathanson, Moreau, Merlet-Benichou, & Gilbert, 2000) and vitamin A deficiency (Lelievre-Pegorier et al, 1998) impair kidney development and result in reduced nephron number in the offspring. In animal models, IUGR produced by partial uterine artery ligation leads to a permanent nephron deficit (Merlet-Benichou, Gilbert, Muffat-Joly, Lelievre-Pegorier, & Leroy, 1994).…”

Section: Early Development Explanationsmentioning

confidence: 99%

Exploring the pathways leading from disadvantage to end-stage renal disease for Indigenous Australians

Cass

Cunningham

Snelling³

et al. 2004

Social Science & Medicine

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Indigenous Australians are disadvantaged, relative to other Australians, over a range of socio-economic and health measures. The age-and sex-adjusted incidence of end-stage renal disease (ESRD) -the irreversible preterminal phase of chronic renal failure -is almost nine times higher amongst Indigenous than it is amongst non-indigenous Australians. A striking gradient exists from urban to remote regions, where the standardised ESRD incidence is from 20 to more than 30 times the national incidence. We discuss the profound impact of renal disease on Indigenous Australians and their communities. We explore the linkages between disadvantage, often accompanied by geographic isolation, and both the initiation of renal disease, and its progression to ESRD. Purported explanations for the excess burden of renal disease in indigenous populations can be categorised as:(1) primary renal disease explanations; (2) genetic explanations; (3) early development explanations; and (4) socio-economic explanations.We discuss the strengths and weaknesses of these explanations and suggest a new hypothesis which integrates the existing evidence. We use this hypothesis to illuminate the pathways between disadvantage and the human biological processes which culminate in ESRD, and to propose prevention strategies across the life-course of Indigenous Australians to reduce their ESRD risk.Our hypothesis is likely to be relevant to an understanding of patterns of renal disease in other high-risk populations, particularly indigenous people in the developed world and people in developing countries. Furthermore, analogous pathways might be relevant to other chronic diseases, such as diabetes and cardiovascular disease. If we are able to confirm the various pathways from disadvantage to human biology, we will be better placed to advocate evidence-based interventions, both within and beyond the scope of the health-care system, to address the excess burden of renal and other chronic diseases among affected populations.

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Effects of Maternal Protein Restriction on the Kidney of the Newborn Young of Rats

Cited by 118 publications

References 14 publications

Maternal Protein Restriction Suppresses the Newborn Renin-Angiotensin System and Programs Adult Hypertension in Rats

Maternal Protein Restriction Suppresses the Newborn Renin-Angiotensin System and Programs Adult Hypertension in Rats

Blood pressure and kidney size in term newborns with intrauterine growth restriction

Exploring the pathways leading from disadvantage to end-stage renal disease for Indigenous Australians

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