Hostname: page-component-74656f9884-c52kr Total loading time: 0 Render date: 2026-11-08T11:08:02.043Z Has data issue: false hasContentIssue false
  • English
  • Français

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

Part of: French DOHaD

Published online by Cambridge University Press:  06 August 2018

C. Juvet ,
U. Simeoni ,
C. Yzydorczyk ,
B. Siddeek ,
J.-B. Armengaud ,
K. Nardou ,
P. Juvet ,
M. Benahmed ,
F. Cachat  and
H. Chehade
C. Juvet*
Affiliation:
Division of Pediatrics, DOHaD Laboratory, woman-mother-child department, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland Division of Pediatrics, pediatric nephrology unit, woman-mother-child department, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
U. Simeoni
Affiliation:
Division of Pediatrics, DOHaD Laboratory, woman-mother-child department, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland Division of Pediatrics, pediatric nephrology unit, woman-mother-child department, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland Division of Pediatrics, woman-mother-child department, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
C. Yzydorczyk
Affiliation:
Division of Pediatrics, DOHaD Laboratory, woman-mother-child department, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
B. Siddeek
Affiliation:
Division of Pediatrics, DOHaD Laboratory, woman-mother-child department, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
J.-B. Armengaud
Affiliation:
Division of Pediatrics, DOHaD Laboratory, woman-mother-child department, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland Division of Pediatrics, pediatric nephrology unit, woman-mother-child department, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland Division of Pediatrics, woman-mother-child department, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
K. Nardou
Affiliation:
Division of Pediatrics, DOHaD Laboratory, woman-mother-child department, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland Division of Pediatrics, pediatric nephrology unit, woman-mother-child department, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
P. Juvet
Affiliation:
Division of Pediatrics, woman-mother-child department, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
M. Benahmed
Affiliation:
Division of Pediatrics, DOHaD Laboratory, woman-mother-child department, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
F. Cachat
Affiliation:
Division of Pediatrics, pediatric nephrology unit, woman-mother-child department, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
H. Chehade
Affiliation:
Division of Pediatrics, DOHaD Laboratory, woman-mother-child department, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland Division of Pediatrics, pediatric nephrology unit, woman-mother-child department, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
*
Address for correspondence: C. Juvet, DOHaD Laboratory, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Rue du Bugnon 27, 1005 Lausanne, Switzerland. E-mail: Christian.Juvet@chuv.ch
Rights & Permissions [Opens in a new window]

Abstract

Intrauterine growth restriction (IUGR) has been identified as a risk factor for adult chronic kidney disease (CKD), including hypertension (HTN). Accelerated postnatal catch-up growth superimposed to IUGR has been shown to further increase the risk of CKD and HTN. Although the impact of excessive postnatal growth without previous IUGR is less clear, excessive postnatal overfeeding in experimental animals shows a strong impact on the risk of CKD and HTN in adulthood. On the other hand, food restriction in the postnatal period seems to have a protective effect on CKD programming. All these effects are mediated at least partially by the activation of the renin–angiotensin system, leptin and neuropeptide Y (NPY) signaling and profibrotic pathways. Early nutrition, especially in the postnatal period has a significant impact on the risk of CKD and HTN at adulthood and should receive specific attention in the prevention of CKD and HTN.

Keywords

chronic kidney diseaseDevelopmental Origins of Health and Diseasehypertensionprogramming

Information

Type
Review
Information
Journal of Developmental Origins of Health and Disease , Volume 9 , Issue 6 , December 2018 , pp. 598 - 614
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2018 

Introduction

Noncommunicable diseases (NCDs), including chronic kidney disease (CKD), are the major and growing cause of morbidity and mortality worldwide. According to the Centers for Disease Control and Prevention database, NCDs are responsible for more than 68% of the deaths observed worldwide and 75% of deaths in low- and middle-income countries. Besides genetic inheritance, studies have shown that early life environment, in particular during the periconceptional, fetal and postnatal periods, can impact the development of NCDs in adulthood. These observations gave rise to the Developmental Origins of Health and Disease theory.Reference Barker, Winter, Osmond, Margetts and Simmonds 1 – Reference Lackland, Bendall, Osmond, Egan and Barker 3

Several studies have highlighted that environmental factors during intrauterine life can result in lower nephron endowment, decreased renal function, arterial hypertension (HTN) and CKD programming.Reference Lackland, Bendall, Osmond, Egan and Barker 3 – Reference Boubred, Saint-Faust and Buffat 6 According to Brenner’s hypothesis, numerous deleterious intrauterine conditions, and in particular growth restriction during nephrogenesis, are associated with a decreased nephron number, resulting in a reduced filtration surface which in turn promotes single nephron hyperfiltration, glomerular sclerosis, albuminuria, CKD and HTN.Reference Luyckx and Brenner 7 – 15 Furthermore, lower nephron number decreases the renal reserve, resulting in a higher vulnerability to other comorbidities (i.e. diabetes mellitus and/or obesity) later in life. A reduced nephron endowment may be secondary to deleterious intrauterine conditions, such as low birth weight (LBW), glucocorticoid administration,Reference Moritz, Singh, Probyn and Denton 16 maternal diabetes,Reference Simeoni and Barker 17 or maternal vitamin A deficiency.Reference Lelievre-Pegorier, Vilar and Ferrier 18 Furthermore, the genetic background also influences the congenital nephron endowment, as shown by Hoy et al. in the aboriginal population, which has a significantly lower nephron number compared with the Black or White population.Reference Hoy, Bertram and Denton 19 , Reference Hoy, Ingelfinger and Hallan 20 However, this observation could partly be mediated by a higher prevalence of intrauterine growth restriction (IUGR) in this population.Reference Hoy, Kincaid-Smith and Hughson 21

On the other hand, the long-term effects of excessive postnatal nutrition and accelerated postnatal growth, per se or superimposed on IUGR, have been less studied, although they act synergistically in the programming of HTN and CKD.Reference Luyckx and Brenner 7 However, optimal postnatal nutrition and catch-up growth are associated with better neurodevelopmental outcomes (IQ) in LBW infants.Reference Lucas, Morley and Cole 22 , Reference Pylipow, Spector and Puumala 23 The optimal nutrition strategy and growth trajectory in LBW infants is therefore still controversial. We aim to discuss in this narrative review the main epidemiological and experimental findings published so far regarding the effects of early postnatal nutrition on long-term renal outcomes, including blood pressure (BP). We also discuss the pathogenic and epigenetic mechanisms involved in the CKD/HTN programming related to early postnatal nutrition.

Methods

In this narrative review, we searched the Medline literature Database through PubMed from its inception until December 2017. Set of keywords (free text) included ‘Childhood growth AND adult AND blood pressure,’ ‘Postnatal overfeeding AND kidney,’ ‘Postnatal AND nutrition AND kidney.’ Papers in other language than English were excluded. References from retrieved papers were also screened.

Papers were included if they explored the epidemiological, physiological, cellular or molecular aspects of CKD programming in relation to postnatal nutrition. Human studies were included if they analyzed the effect of early postnatal nutrition during the postnatal period of the first 1000 days of life on CKD and HTN programming. In this setting we considered postnatal weight changes as a surrogate marker of postnatal nutrition. Articles were selected after reading of the title and/or abstract by one author (C.J.). A flowchart depicting the included and excluded papers is reported in Fig. 1.

Fig. 1

Flow chart of identified, included and excluded studies.

Results

Human studies

Effect of postnatal catch-up growth on BP in children with LBW

Several epidemiological human studies have focused on the association between growth patterns in infancy and childhood and the risk of HTN development. This risk is increased in children born with LBW, whether it is due to IUGR, prematurity or both, followed by rapid early growth (catch-up growth).Reference Luyckx and Brenner 7 , Reference Barker, Forsen, Eriksson and Osmond 24 , Reference Taine, Stengel and Forhan 25 Taine et al. Reference Taine, Stengel and Forhan 25 recently showed in a prospective cohort study that rapid weight gain velocity between birth and the age of 4 months was associated with a higher systolic blood pressure (SBP) at 5 years of age, but only in children who were small for gestational age at birth (test for interaction, P=0.003). The authors found no association between weight gain after 4 months of age and later BP. The same association has been described in several other studies (Table 1).Reference Zhao, Shu and Jin 26 – Reference Singhal, Cole and Fewtrell 28 The association between high BP and a growth trajectory from LBW to normal or high weight/body mass index (BMI) at mid-childhood is further described by studies that longitudinally monitored infancy and childhood growth.Reference Barker, Forsen, Eriksson and Osmond 24 , Reference Eriksson, Forsen, Kajantie, Osmond and Barker 29 – Reference Huang, Burrows, Mori, Oddy and Beilin 31 The risk of HTN and/or CKD also increases when LBW is associated to prematurity as demonstrated by Tauzin et al.Reference Tauzin, Rossi and Grosse 32 Together, these studies show the negative impact of rapid weight gain after LBW on HTN programming.

Table 1

Summary of the main epidemiological findings in human studies about associations between growth patterns and renal outcomes

eGFR, estimated glomerular filtration rate; GFR, glomerular filtration rate; BW, birth weight; LBW, low birth weight; HTN, hypertension; BP, blood pressure; SGA, small for gestational age; OR, odds ratio; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; MAP, mean arterial pressure; AGA, appropriate for gestational age; EDEN, étude des déterminants pré et post natals précoces de la santé et du développement de l’ENfant; SWEDES, stockholm weight development study; MSC NSHD, medical research council national survey of health and development

Females and males were included, unless specified otherwise.

Effect of postnatal excessive growth on BP in children with normal birth weight (BW)

Although most studies point towards a positive association between higher weight gain in the first 2 years of life and HTN in adulthood, other studies describe a protective effect of increased growth in infancy and early childhood. In total, five studies found a significant association between increased weight gain in different periods between birth and 4 years of age, and lower BP in adolescence and adulthood (Table 1).Reference Eriksson, Forsen, Kajantie, Osmond and Barker 29 , Reference Cruickshank, Mzayek and Liu 33 – Reference Hardy, Wadsworth, Langenberg and Kuh 36 However, the vast majority of studies, including a meta-analysis of five cohort studies reports that postnatal weight gain is associated with higher BP later in life, especially when early and excessiveReference Barker, Forsen, Eriksson and Osmond 24 , Reference Huang, Burrows, Mori, Oddy and Beilin 31 , Reference Adair, Martorell and Stein 37 – Reference de Beer, Vrijkotte and Fall 53 (Table 1).

In these cohort studies, it is extremely difficult to attribute the development of adulthood HTN to an isolated excessive early weight gain v. a persistent obesity (and more importantly obesity at the time of HTN diagnosis). A Senegalese study in a population where adult overweight was exceptional (0.1%) still found an association between early weight gain and adult SBP.Reference Cournil, Coly, Diallo and Simondon 54 On the other hand, using conditional regression, Chiolero et al. demonstrated that, at all ages, BP is more responsive to recent rather than earlier weight changes,Reference Chiolero, Paradis and Bovet 55 although the true answer might be more complicated than it seems.Reference Chiolero, Kaufman and Paradis 56

However, the above-mentioned studies present several limitations, as they are extremely heterogeneous in their design: timing of BP measurement varies between early childhood to middle adulthood. Additionally, while some studies assessed BP as a continuous variable, others examined the odds of HTN. The same heterogeneity applies to the adjustment to the current weight or BMI, to take into account the ‘excess’ BP, not attributable to the current obesity of the individuals. This renders difficult to compare studies and to reach firm conclusions. Indeed, many researchers found no association between excessive weight gain in children born with normal weight and later HTN, after adjustment for BMI (at the time of BP measurement). Other limitations are confounding factors such as maternal pathology, maternal tobacco use or family history of HTN, which are very inconstantly reported. Furthermore, most of these studies do not address aspects of infant feeding.

HTN after famine exposure

Being exposed to famine in utero is known to be associated with increased risk of HTN in adulthood probably via the development of IUGR.Reference Stein, Zybert, van der Pal-de Bruin and Lumey 57 However it is less clear if this window of vulnerability to growth restriction extends to extrauterine life. This question was recently explored in a meta-analysis including 16 observational studies.Reference Xin, Yao, Yang and Zhang 58 It appears that postnatal famine exposure also leads to a higher risk of adult HTN in Asian population. However, the vast majority of the included studies find that adult weight after postnatal famine exposure is either unchanged or increased. Therefore, catch-up growth must occur at some point, raising the question whether adult HTN is due to famine exposure itself or to subsequent catch-up growth. Notably, the included studies mostly adjust their results for adult BMI, suggesting that the effect of famine is not mediated by changes in adult BMI.

Breastfeeding, qualitative aspects of food intake and HTN

In addition to weight and BMI in infancy and childhood, qualitative nutritional aspects should be considered. A large meta-analysis including 15 studies found that breastfeeding is associated with lower SBP and diastolic BP (DBP) later in life.Reference Martin, Gunnell and Smith 59 As longer breastfeeding is also associated with lower adult BMI, mediated by lower early growth, the effect of breastfeeding on adult BP could also be indirect, due to lower adult BMI.Reference Fergusson, McLeod and Horwood 60 Additionally, salt content may play a role as mother’s milk contains less salt than formula milk. In a randomized controlled trial, low sodium diet (in average 0.89 v. 2.5 mmol/day) in the first 6 months of life has been shown to be associated with lower SBP at 15 years of age.Reference Geleijnse, Hofman and Witteman 61 As early diet is known to affect taste preference later in life,Reference Maslin, Grimshaw and Oliver 62 one could hypothesize that this effect could be partially mediated by lower sodium intake later in life. However, sodium excretion in this study was in the normal range in both experimental groups, but the low sodium group had nonsignificantly lower sodium excretion. Therefore, this mechanism cannot be definitively confirmed, although animal experiments indicate that salt preference can be programmed early in life.Reference Smriga, Kameishi and Torii 63

Furthermore, long-chain polyunsaturated fatty acids (LCPUFA), present in mother’s milkReference Brenna, Varamini and Jensen 64 are likely to impact later BP. Indeed, LCPUFA supplementation in formula in the first 4 months of life resulted in lower BP at 6 years of age.Reference Forsyth, Willatts and Agostoni 65 As breastfed infants have higher LCPUFA plasma concentration, this is likely to contribute to the protective effect of breastfeeding on BP (note that this study tested breastfeeding v. formula not supplemented with LCPUFA).Reference Decsi, Thiel and Koletzko 66

The impact of other food components such as fiber and protein intake was investigated in a Dutch cohort study. Although fiber intake at 1 year of age had no effect on BP at mid-childhood, higher protein intake was associated with lower DBP at 6 years of age, which was at the limit of significance, and no association with SBP was found.Reference van Gijssel, Braun and Kiefte-de Jong 67 , Reference Voortman, van den Hooven and Tielemans 68 This result alone provides too weak evidence to conclude on a potential role of early protein intake on later BP, especially, when considering that a randomized control trial, however, conducted in a population of children born small for gestational age, found opposite results.Reference Singhal, Cole and Fewtrell 28 This trial examined the effects of increased protein content in infant formula on the risk of HTN development (68 kcal, 1.4 g of proteins per 100 ml v. 72 kcal, 1.8 g of proteins per 100 ml). Children fed a nutrient-rich formula during infancy developed higher DBP and increased mean arterial pressure at 6–8 years of age compared with those fed a standard formula. This effect remained significant after adjustment for current weight.Reference Singhal, Cole and Fewtrell 28

Role of early weight gain on glomerular filtration rate (GFR)

There is no clear data between early weight gain in children with normal BW and the development of CKD in adulthood. A few studies have investigated the role of early weight or height and their impact on GFR in childhood. Bakker et al. Reference Bakker, Gaillard and Franco 69 demonstrated that a higher body length and weight z score at 2, 3 and 4 years of age was associated with a higher GFR at 6 years of age. Bacchetta et al. Reference Bacchetta, Harambat and Dubourg 70 showed that premature infants (<30 weeks of gestation or BW <1000 g) with extrauterine growth retardation (but no IUGR) had significantly decreased inulin clearances at 7 years of age, similarly to those born with IUGR (in both groups inulin clearances were still in the lower normal range). In a randomized clinical trial, infants fed a high protein formula (average protein intake at 6 months of age: 3 g/kg/day) had higher kidney volume at 6 months of life compared with infants fed a low protein formula (average protein intake at 6 months of age: 1.94 g/kg/day).Reference Escribano, Luque and Ferre 71 However, estimated GFR was not significantly different between low and high protein group in this study, even though higher renal volume is known to be associated to higher GFR.Reference Bakker, Kooijman and van der Heijden 72 , Reference Adibi, Adibi and Khosravi 73

Conclusion

The vast majority of studies reports evidence, on an epidemiological level, that postnatal excessive weight gain in the first 1000 days of life, until the second birthday, is associated with later development of HTN in adulthood, rarely in childhood. Greatly inadequate early weight gain, as observed in the famines, is also associated with HTN later in life, although it is difficult to distinguish whether this may be due to subsequent catch-up growth rather than famine itself. If excessive weight gain in early life is associated with the development of CKD remains to be demonstrated.

Animal studies

Overfeeding

Animal models have demonstrated that IUGR can lead to the development of CKD and HTN in adulthood.Reference Ojeda, Grigore and Alexander 74 In addition, postnatal overfeeding or excessive weight gain velocity has a negative impact on renal function and conveys an increased risk of adulthood HTN development. Male rats born after IUGR have higher BP values, proteinuria and glomerular volume in adulthood, and these abnormalities are further increased by overfeeding in the immediate postnatal period and/or in adulthood (induced by hypercaloric or hyperlipidic feeding respectively).Reference Shen, Xu, Wei, Chen and Liu 75 , Reference Vickers, Breier, Cutfield, Hofman and Gluckman 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.Reference Boubred, Delamaire and Buffat 77 The same adverse outcomes were observed after overfeeding (by litter size reduction) alone, but not after IUGR alone.Reference Boubred, Daniel and Buffat 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. A reduction of creatinine clearance was only observed in males and when both conditions (IUGR and early overfeeding) were present.Reference Boubred, Daniel and Buffat 78

In another rat model of early postnatal overfeeding during lactation (via litter size reduction) without IUGR, a higher nephron number, a smaller glomerular volume, a higher BP values in both sexes, and a higher proteinuria and glomerulosclerosis in males were observed.Reference Boubred, Buffat and Feuerstein 79 Another study with the same experimental settings found similar results and a decreased creatinine clearance at 12 months of age.Reference Yim, Ha and Bae 80 , Reference Yim, Yoo, Bae, Hong and Lee 81 Notably nephron number was decreased. In another animal model, early overfed animals after litter size reduction to six animals had a lower SBP, higher proteinuria, more glomerulosclerosis and decreased GFR compared with the control group at 70 days of life.Reference Alcazar, Boehler and Rother 82

Together, these animal studies clearly demonstrate that postnatal overfeeding contributes to CKD programming in adulthood in both animals born with IUGR and in animals with a normal BW. It has been observed that nephron number is often decreased in IUGR animal models, whereas it can be increased or decreased in animals with early postnatal overfeeding. This suggests different mechanisms involved in pre- and postnatal programming of CKD, which can act synergistically when IUGR and postnatal overfeeding are combined.

Importantly, it should be considered that early postnatal overfeeding globally affects the organism’s function. Indeed, the model of litter size reduction in rodents, used by the previously mentioned studies, results in increased milk availability and thus overfeeding until weaning after which animals are fed the same standard chow throughout adulthood. This model is known to have multiple effects, as it affects appetite regulation, the hypothalamic pituitary adrenal axis, as well as lipid and glucose metabolism, which are all likely to further impact renal function.Reference Habbout, Li, Rochette and Vergely 83

Furthermore, this condition is mostly associated with higher body weight throughout life,Reference Boubred, Daniel and Buffat 78 , Reference Boubred, Buffat and Feuerstein 79 , Reference Alcazar, Boehler and Rother 82 , Reference Alejandre Alcazar, Boehler and Amann 84 although a later normalization of weight is also described.Reference Yim, Yoo, Bae, Hong and Lee 81 This raises the same question than human studies, whether early postnatal overfeeding directly or indirectly affects BP and CKD. As the global effects of early postnatal overfeeding are extensively reviewed elsewhere,Reference Habbout, Li, Rochette and Vergely 83 this narrative review focuses on the specific intrarenal modifications involved in CKD programming after early postnatal nutritional intervention.

Undernutrition

Regarding postnatal undernutrition, Hoppe et al. performed a study in which IUGR pups obtained after maternal low protein diet during gestation and lactation were continuously exposed to low protein diet throughout life. This group had a reduced nephron number (−31%) and glomerular volume (−24%), as well as lower BP (−8 mmHg=6%), when compared with the control group.Reference Hoppe, Evans and Moritz 85 In two other studies of postnatal transient food restriction by cross-fostering on a dam on a low protein diet throughout pregnancy and suckling period, underfed animals developed lower albuminuria later in life.Reference Petry, Jennings, James, Hales and Ozanne 86 , Reference Tarry-Adkins, Joles and Chen 87 This demonstrates that food restriction not only improves renal outcome when applied transiently, but can also correct prenatally programmed HTN.

Notably, in a study in which litter size reduction led to paradoxical growth restriction followed by catch-up growth in the post suckling period, exposed animals developed higher SBP and lower glomerular count.Reference Wlodek, Westcott, Siebel, Owens and Moritz 88 These findings resemble the phenotype observed in IUGR followed by catch-up growth. Indeed, in this setting too, growth restriction occurs during nephrogenesis (which is still ongoing postnatally in rats) and is followed by catch-up growth.

The different findings in the two previously cited studies in which postnatal growth restriction was associated with better renal outcome, could be explained by the fact that the animals either kept a lower weight throughout life, or caught-up during the suckling period when suckled by a control dam, providing normal lactational environment.Reference Petry, Jennings, James, Hales and Ozanne 86 , Reference Tarry-Adkins, Joles and Chen 87

Impact of lactational environment on renal outcomes

To further study the impact of nutritional environment, a cross-foster study investigated the effect of lactational environment on renal outcomes in pups born with IUGR (induced by uterine vessel ligation (UVL) at day 18 of gestation) or control in a reduced litter. Notably in this study, litter size reduction did not lead to increased weight gain. Control pups in a reduced litter suckling a dam which gave birth to IUGR pups after UVL had higher BP at 20 weeks of age than pups in the same condition but suckled by a control dam. This was associated with a growth pattern of nonsignificantly lower weight gain in the late suckling period, followed by faster weight gain, but nonsignificantly lower weight in adulthood. In contrast, pups with IUGR after maternal UVL suckled by a control dam had normal nephron number and BP at 20 weeks of age (compared with controls), whereas IUGR pups suckled by UVL dams had higher BP and lower nephron number.Reference Wlodek, Mibus and Tan 89 This demonstrates that a normal lactational environment can rescue prenatally programmed HTN in this animal model and also suggests that maternal conditions (i.e. placental insufficiency) do not only impact fetal development, but further influence milk composition in the postnatal period. This hypothesis is supported by Peter et al. Reference Peter, Gugusheff, Wooldridge, Gatford and Muhlhausler 90 who demonstrated a higher protein content in ewe’s milk after placental insufficiency. Not only quantity, but also quality of the milk may play an important role in the development of CKD later in life. Boubred et al.Reference Boubred, Delamaire and Buffat 77 elegantly showed that feeding IUGR pups with a high-protein milk (13.1 g and 172 kcal v. 8.7 g and 155 kcal per 100 ml) early in life promotes CKD development, again suggesting an important role of the quality of nutrition in the development of kidney diseases.

The main findings of animal studies investigating the impact of early postnatal nutrition on CKD and HTN programming are summarized in Table 2.

Table 2

Summary of the main findings in animal studies about early postnatal nutrition and renal outcome later in life

These studies examined exclusively males, except Boubred et al.Reference Boubred, Daniel and Buffat 78 and Boubred et al.Reference Boubred, Buffat and Feuerstein 79

IUGR, intrauterine growth restriction; LPD, low protein diet; OF, overfeeding; CTRL, control; HPD, high protein diet; BP, blood pressure; SBP, systolic blood pressure; LSR X, litter size reduction to X pups; PAI, plasminogen activator inhibitor; MMP, metalloprotease; AT, AT1, AT1a, AT1b, AT2, angiotensin II receptor and isoforms; ANG II, angiotensin II; TIMP, tissue inhibitor of metalloproteases; TNF, tumor necrosis factor; OPN, osteopontin; UVL, bilateral uterine vessel (artery and vein) ligation; eGFR, estimated glomerular filtration rate; Y1, 2, NPY receptor; SOCS-3, suppressor of cytokine signaling 3; NPY, neuropeptide Y; Agt, angiotensinogen; Gpx, glutathione peroxidase; GR, glutathione reductase; MnSOD, manganese superoxide dismutase.; eNOS, endothelial nitric oxide synthase.

Mechanistic aspects

The following section of this narrative review addresses the different molecular intrarenal systems that contribute to CKD programming after early postnatal overfeeding. The systemic effects of early postnatal overfeeding are reviewed elsewhere.Reference Habbout, Li, Rochette and Vergely 83

Renin-angiotensin system (RAS)

The RAS is tightly involved in BP regulation, mediated by effects on vasoconstriction, renal perfusion and natriuresis. Most of these BP-raising effects are obtained through angiotensin 2 receptor type 1 receptor (AT1) signaling, whereas angiotensin 2 receptor type 2 receptor (AT2) negatively modulates the effects of AT1.Reference Padia and Carey 91 Five different studies examined changes in the RAS after early postnatal overfeeding by litter size reduction in male rats. Renin was upregulated early in the first month of life, followed by normalization or even decrease of renin levels at 12 months.Reference Yim, Ha and Bae 80 , Reference Yim, Yoo, Bae, Hong and Lee 81 , Reference Alejandre Alcazar, Boehler and Amann 84 , Reference Yim, Ha and Bae 92 In this model, AT2 expression increased at 28 days of life, possibly as a counter-regulation for increased renin, followed by normalization,Reference Yim, Ha and Bae 80 , Reference Yim, Yoo, Bae, Hong and Lee 81 , Reference Yim, Ha and Bae 92 while described as unchanged in renal cortex in another study.Reference Granado, Amor and Fernandez 93 In a similar experimental setting, kidney β-1 adrenoreceptor mRNA was downregulated at 70 days of life,Reference Alcazar, Boehler and Rother 82 which could contribute to the later normalization or even a decreased renin secretion.Reference Torretti 94

Results about the impact of postnatal nutrition on AT1 expression are somewhat conflicting. After litter size reduction, AT1 is increased in renal cortex, followed by a decrease in its levels afterwards.Reference Granado, Amor and Fernandez 93 In one study, paradoxical postnatal growth restriction (after litter size reduction) followed by a catch-up growth did not alter AT1 mRNA expression.Reference Wlodek, Westcott, Siebel, Owens and Moritz 88 However, control pups from a reduced litter cross-fostered on a dam, who underwent bilateral UVL during pregnancy, had upregulated renal AT1a-b mRNA expression and AT1 protein synthesis and higher BP compared with pups from a reduced litter suckled by a control dam, suggesting that alteration in lactational environment can contribute to the development of HTN via changes in the RAS system.Reference Wlodek, Mibus and Tan 89

Transient postnatal administration of RAS blockers seems to prevent the development of programmed HTN after IUGR.Reference Sherman and Langley-Evans 95 , Reference Sherman and Langley-Evans 96 This is not the case for HTN following isolated early postnatal overfeeding.Reference Yim, Yoo, Bae and Hong 97

In conclusion, the RAS system is modified by IUGR and by postnatal nutrition as well. In animal models with IUGR, an early RAS suppression followed by RAS hyper expression has been observed, which could participate in the HTN programming.Reference Bagby 10 , Reference Sherman and Langley-Evans 95 , Reference Sherman and Langley-Evans 96 , Reference Simeoni, Ligi, Buffat and Boubred 98 – Reference Woods, Ingelfinger, Nyengaard and Rasch 100 However, this expression profile does not correspond to the modifications observed after early postnatal overfeeding.

Oxidative stress, telomere shortening and senescence

Cellular senescence is an irreversible arrest of cell proliferation, characterized by several markers such as telomere shortening. Senescence can be induced prematurely by exposure to oxidative stress, caused by imbalance between reactive oxygen species and antioxidant defenses.Reference Correia-Melo, Hewitt and Passos 101 Cellular senescence is associated with renal aging, CKD development and early morbidity and mortality.Reference Sturmlechner, Durik, Sieben, Baker and van Deursen 102 Continuous food restriction or overfeeding have been shown to impact the levels and activity of several antioxidants and markers of oxidative stress.Reference Walsh, Shi and Van Remmen 103 , Reference Samocha-Bonet, Campbell and Mori 104 Postnatal growth retardation in male rats is associated with significantly longer kidney telomeres and an increased longevity. On the other hand, growth retardation during the fetal life followed by postnatal catch-up growth is associated with shorter kidney telomeres and a shorter lifespan.Reference Jennings, Ozanne, Dorling and Hales 105 Food restriction in the lactation period confers nephroprotective effects in the male rat with significantly decreased albuminuria compared with controls. This was associated with lower levels of short telomeres in the renal cortex at 12 months of age and increased antioxidant enzymes (glutathione peroxidase and manganese superoxide dismutase) expression at 3 and 12 months, respectively.Reference Tarry-Adkins, Joles and Chen 87 The same association between lower albuminuria, lower levels of short telomeres and higher antioxidant expression was observed in females compared with males in another animal study evaluating gender disparity in CKD. In this study, expression of senescence promoting factors p53 and p21 significantly increased with age in males, but not in females, and manganese superoxide dismutase (MnSOD) and glutathione reductase (GR) expression were more elevated in female compared with male kidney cortex.Reference Tarry-Adkins, Ozanne, Norden, Cherif and Hales 106

In conclusion, postnatal overfeeding seems to affect the cellular response to oxidative stress, which is in turn associated with telomere shortening and resulting in cellular senescence.

Inflammation and profibrotic factors

Several factors playing a key role in inflammation and fibrosis, and thus leading to glomerulosclerosis and interstitial fibrosis, have been investigated in different models of postnatal overfeeding.Reference Yim, Ha and Bae 80 – Reference Alcazar, Boehler and Rother 82 , Reference Yim, Ha and Bae 92

Postnatal overfeeding of male rats resulted in increased macrophage infiltration, associated with increased macrophage attracting factors such as tumor necrosis factor α and osteopontin. This was associated with higher levels of glomerulosclerosis.Reference Yim, Ha and Bae 80

Several modifications of factors involved in extracellular matrix deposition and remodeling were also observed after early postnatal overfeeding. In different animal experiments of postnatal overfeeding, transient modifications in plasmin activator inhibitor (PAI-1), metalloprotease-9 and tissue inhibitor of metalloproteases were observed, followed by a normalization of their levels at 6 or 12 monthsReference Yim, Ha and Bae 80 – Reference Alcazar, Boehler and Rother 82 , Reference Yim, Ha and Bae 92 (for details see Table 2).

In conclusion, in several animal models, postnatal overfeeding is associated with an upregulation of pro-inflammatory proteins, which is likely to contribute to subsequent glomerular sclerosis, interstitial inflammation and fibrosis.

Leptin

Leptin is an important hormone for the regulation of metabolism, appetite and energy balance, with direct effects on the kidney, promoting glomerulosclerosis and proteinuria.Reference Wolf, Chen, Han and Ziyadeh 107 , Reference Beltowski, Jamroz-Wisniewska, Borkowska and Wojcicka 108 In animal models of early postnatal overfeeding by litter size reduction, increased leptin expression was observed 1 week after the end of early overfeeding, returning to normal levels at 70 days and 12 months of age.Reference Yim, Yoo, Bae, Hong and Lee 81 , Reference Alcazar, Boehler and Rother 82 , Reference Yim, Ha and Bae 92 A post-receptor downregulation of leptin signaling through suppressor of cytokine signaling 3 was observed at 70 days of age, potentially explaining the resistance to leptin.Reference Alcazar, Boehler and Rother 82

Leptin inhibits neuropeptide Y (NPY), an orexigenic factor with multiple effects on renal blood flow, sodium transport and renin secretion.Reference Bischoff and Michel 109 NPY levels increased after early overfeeding, consistent with leptin resistance. Simultaneously, NPY receptors were downregulated, resulting in lower NPY pathway signaling, which was associated with increased natriuresis.Reference Alejandre Alcazar, Boehler and Amann 84 This can be explained by a lower Na/K ATPase activity secondary to leptin and NPY resistance.Reference Beltowski, Jamroz-Wisniewska, Borkowska and Wojcicka 108 , Reference Bischoff and Michel 109 Yet, increased natriuresis should prevent HTN. Unfortunately, BP was not measured in this model.

In conclusion, early overfeeding is associated with an early increase in leptin and NPY expression, and at the same time with leptin and NPY resistance, which is also associated with an increased natriuresis. Their effects on glomerulosclerosis, proteinuria and BP remain to be studied.

Vascular dysfunction

A recent study examined the renal artery after early postnatal overfeeding by litter size reduction, however without assessing the phenotype of BP or renal function.Reference Granado, Amor and Fernandez 93 At weaning, when overfeeding ended, vascular contractile response to angiotensin II (ANG II) was increased, with concomitant decrease in AT1 and AT2 mRNA. On the contrary, at 5 months of life, contractile response to ANG II was decreased with concomitant increase in AT1 and AT2 mRNA. These alterations of contractility may be mediated by the modifications of AT2, known to counteract AT1 effects. However, AT1 and AT2 protein levels and their signaling function were not assessed. Furthermore, GFR is also determined by the tonus of the efferent arteriole, which was not examined. Therefore, the functional consequences of these observed contractility modifications are difficult to evaluate.

Giving insight for the modification of systemic vaculature, the cremaster muscle was examined in the same setting in male hamsters. Postnatally overfed hamsters had a lower vasodilatation in response to acetylcholine, but not to a NO donor (sodium nitroprusside) at 21 weeks of age, which indicates endothelial-dependent vascular dysfunction.Reference Leite, Kraemer-Aguiar and Boa 110 Hypothesizing that this modification is generalized in the body, this is likely to contribute to a higher BP and also impacts renal blood flow, and thus the kidney’s function.

Sex specificity of CKD programming

Studies examining this sex specificity are scarce, as most previously cited studies included only male subjects. Sex specificity of CKD programming after early postnatal overfeeding was investigated in two studies, showing that programming differs between sexes, as females had no significant change in BP, renal function and proteinuria, contrary to males.Reference Boubred, Daniel and Buffat 78 , Reference Boubred, Buffat and Feuerstein 79 The molecular mechanisms underlying sex specificity of programming remain to be investigated. However, several components of the previously discussed molecular pathways are known to be expressed differentially in females and males, thus representing promising candidates. For example, AT2 is encoded on the X chromosome. As AT2 counteracts the main effects of the RAS which are mediated by AT1, higher expression in females could have a protective effect.Reference Padia and Carey 91 Furthermore, increased levels of antioxidant enzymes (GR and MnSOD) were found in the female rat kidney, which could protect them against oxidative stress, compared with the male rat kidney. Aging males had higher albuminuria, which was associated with higher levels of short telomeres and an increase in senescence promoting factors p53 and p21.Reference Tarry-Adkins, Ozanne, Norden, Cherif and Hales 106 Renal leptin signaling in rats fed a ‘cafeteria diet’ also exhibits sexual dimorphism. Both males and females subjected to a neonatal testosterone treatment had higher BP compared with females, when exposed to such a diet. In these two groups, leptin binding sites in the renal medulla were reduced although leptin receptor mRNA was unchanged, which was inversely correlated with plasma leptin levels.Reference Coatmellec-Taglioni, Dausse, Giudicelli and Ribiere 111 Thus, testosterone induced sexual dimorphism in leptin signaling may contribute to a higher BP after cafeteria feeding.

Epigenetics

Epigenetic regulation which affects gene expression is mediated by several mechanisms, such as DNA methylation, histone acetylation and the presence of micro RNA. Epidemiological studies have shown that BW is influenced by living conditions of previous generations, suggesting epigenetic regulation.Reference Emanuel, Filakti, Alberman and Evans 112 To our knowledge, there is no study investigating epigenetic modifications in the kidney following early postnatal overfeeding. However, several animal studies examined epigenetic changes in the context of IUGR. In a baboon model, IUGR was associated with a disparate effect on global DNA methylation in the fetal kidney: global DNA methylation decreased in the early stage of pregnancy, only to increase at the end of the pregnancy.Reference Unterberger, Szyf, Nathanielsz and Cox 113 In addition, several hypoxia-induced micro RNA subtypes were identified to be expressed differentially in IUGR.Reference Mouillet, Chu and Hubel 114 , Reference Huang, Shen and Xu 115 More specific targets were also identified such as a decrease in P53 promoter methylation in a rat model of IUGR. Furthermore, specific exons of P53 were hypomethylated, which was associated with lower levels of DNA methyltransferase-1. As p53 is a major factor of senescence and apoptosis, this is likely to contribute to lower nephrogenesis and lower nephron endowment after IUGR.Reference Pham, MacLennan and Chiu 116 In addition, AT1b receptor expression in the adrenal gland was upregulated after its promoter was significantly hypomethylated in rats born after IUGR. As ANG II mediates aldosterone secretion in the adrenal gland, this upregulation may contribute to programmed HTN after IUGR.Reference Bogdarina, Welham, King, Burns and Clark 117

In conclusion, epigenetic changes induced by IUGR have been identified and are likely to explain several of the observed molecular changes leading to HTN and CKD. Nevertheless, epigenetic modifications still have to be investigated in the context of altered postnatal nutrition.

Limitations

Our review has several limitations. This is a narrative review with the primary aim of providing an overview of the developmental origins of NCD, in particular CKD and HTN. Formal systematic review and meta-analyses will be necessary to more precisely address the impact of pre- and postnatal weight gain on the development of CKD and HTN later in life.

Additionally, most reported human studies are observational in their design, with their inherent potential bias and confounding factors. The limitation that most human studies did not adjust their findings to adult BMI and other potential confounding factors, such as socioeconomic status, family history of HTN and qualitative nutritional aspects, has been discussed above.

The conclusions that can be drawn from a rodent model on human pathology are limited by the fact that nephrogenesis continues after birth in rodents. Therefore postnatal nutritional intervention can directly interfere with nephrogenesis, which is not the case in humans, except in premature infants.Reference Rodriguez, Gomez and Abitbol 118 Finally, most of the animal studies only examined male animals. The impact of gender on BP development should be better studied, both in human epidemiological and experimental animal studies.

Areas for future research

Future epidemiological and randomized controlled trials should help us decipher between the benefits of early growth on brain and cognitive development on one hand and the danger of HTN and CKD development on the other hand. Additionally, a better understanding of the mechanistic aspects involved in HTN and CKD programming could lead to the identification of early markers and potential therapeutic targets for an early, preventive and personalized approach.

Conclusion

IUGR is associated with CKD programming. In human epidemiological and experimental animal studies, accelerated early weight gain seems to worsen the risk of CKD and HTN in adulthood, especially when this condition is superimposed to IUGR. Animal models of early postnatal overfeeding identified a differential expression of several factors such as the RAS, leptin and NPY signaling, profibrotic pathways and oxidative stress, which likely contribute to CKD progression and higher BP. Many studies included in this review highlight the potential impact of early nutrition intervention in the prevention of CKD development later in life. However, the best nutritional strategy for the newborn who cannot be breastfed remains unclear.

Acknowledgments

None.

Financial Support

C.J. was supported by a scholarship of the Janggen-Pöhn-Stiftung.

Conflicts of Interest

Seven papers from the authors (United States) were included in this narrative review.

Footnotes

†

These authors contributed equally to this work.

References

1. Barker, DJ, Winter, PD, Osmond, C, Margetts, B, Simmonds, SJ. Weight in infancy and death from ischaemic heart disease. Lancet. 1989; 2, 577–580.Google Scholar
2. Roseboom, TJ, van der Meulen, JH, Ravelli, AC, et al. Effects of prenatal exposure to the Dutch famine on adult disease in later life: an overview. Twin Res. 2001; 4, 293–298.Google Scholar
3. Lackland, DT, Bendall, HE, Osmond, C, Egan, BM, Barker, DJ. Low birth weights contribute to high rates of early-onset chronic renal failure in the Southeastern United States. Arch Intern Med. 2000; 160, 1472–1476.Google Scholar
4. Keijzer-Veen, MG, Schrevel, M, Finken, MJ, et al. Microalbuminuria and lower glomerular filtration rate at young adult age in subjects born very premature and after intrauterine growth retardation. J Am Soc Nephrol. 2005; 16, 2762–2768.Google Scholar
5. Dotsch, J, Plank, C, Amann, K. Fetal programming of renal function. Pediatr Nephrol. 2012; 27, 513–520.Google Scholar
6. Boubred, F, Saint-Faust, M, Buffat, C, et al. Developmental origins of chronic renal disease: an integrative hypothesis. Int J Nephrol. 2013; 2013, 346067.Google Scholar
7. Luyckx, VA, Brenner, BM. Birth weight, malnutrition and kidney-associated outcomes – a global concern. Nat Rev Nephrol. 2015; 11, 135–149.Google Scholar
8. Luyckx, VA, Brenner, BM. Low birth weight, nephron number, and kidney disease. Kidney Int Suppl. 2005; 68, S68–S77.Google Scholar
9. Brenner, BM, Garcia, DL, Anderson, S. Glomeruli and blood pressure. Less of one, more the other? Am J Hypertens. 1988; 1(Pt 1), 335–347.Google Scholar
10. Bagby, SP. Maternal nutrition, low nephron number, and hypertension in later life: pathways of nutritional programming. J Nutr. 2007; 137, 1066–1072.Google Scholar
11. Simonetti, GD, Raio, L, Surbek, D, et al. Salt sensitivity of children with low birth weight. Hypertension. 2008; 52, 625–630.Google Scholar
12. de Boer, MP, Ijzerman, RG, de Jongh, RT, et al. Birth weight relates to salt sensitivity of blood pressure in healthy adults. Hypertension. 2008; 51, 928–932.Google Scholar
13. Alwasel, SH, Ashton, N. Prenatal programming of renal sodium handling in the rat. Clin Sci (Lond). 2009; 117, 75–84.Google Scholar
14. Ojeda, NB, Johnson, WR, Dwyer, TM, Alexander, BT. Early renal denervation prevents development of hypertension in growth-restricted offspring. Clin Exp Pharmacol Physiol. 2007; 34, 1212–1216.Google Scholar
15. Luyckx VA, Perico N, Somaschini M, et al. A developmental approach to the prevention of hypertension and kidney disease: a report from the Low Birth Weight and Nephron Number Working Group. Lancet. 2017; 390, 424–428.Google Scholar
16. Moritz, KM, Singh, RR, Probyn, ME, Denton, KM. Developmental programming of a reduced nephron endowment: more than just a baby’s birth weight. Am J Physiol Renal Physiol. 2009; 296, F1–F9.Google Scholar
17. Simeoni, U, Barker, DJ. Offspring of diabetic pregnancy: long-term outcomes. Semin Fetal Neonatal Med. 2009; 14, 119–124.Google Scholar
18. Lelievre-Pegorier, M, Vilar, J, Ferrier, ML, et al. Mild vitamin A deficiency leads to inborn nephron deficit in the rat. Kidney Int. 1998; 54, 1455–1462.Google Scholar
19. Hoy, WE, Bertram, JF, Denton, RD, et al. Nephron number, glomerular volume, renal disease and hypertension. Curr Opin Nephrol Hypertens. 2008; 17, 258–265.Google Scholar
20. Hoy, WE, Ingelfinger, JR, Hallan, S, et al. The early development of the kidney and implications for future health. J Dev Orig Health Dis. 2010; 1, 216–233.Google Scholar
21. Hoy, WE, Kincaid-Smith, P, Hughson, MD, et al. CKD in Aboriginal Australians. Am J Kidney Dis. 2010; 56, 983–993.Google Scholar
22. Lucas, A, Morley, R, Cole, TJ. Randomised trial of early diet in preterm babies and later intelligence quotient. BMJ. 1998; 317, 1481–1487.Google Scholar
23. Pylipow, M, Spector, LG, Puumala, SE, et al. Early postnatal weight gain, intellectual performance, and body mass index at 7 years of age in term infants with intrauterine growth restriction. J Pediatr. 2009; 154, 201–206.Google Scholar
24. Barker, DJ, Forsen, T, Eriksson, JG, Osmond, C. Growth and living conditions in childhood and hypertension in adult life: a longitudinal study. J Hypertens. 2002; 20, 1951–1956.Google Scholar
25. Taine, M, Stengel, B, Forhan, A, et al. Rapid early growth may modulate the association between birth weight and blood pressure at 5 years in the EDEN cohort study. Hypertension. 2016; 68, 859–865.Google Scholar
26. Zhao, M, Shu, XO, Jin, F, et al. Birthweight, childhood growth and hypertension in adulthood. Int J Epidemiol. 2002; 31, 1043–1051.Google Scholar
27. Adair, LS, Cole, TJ. Rapid child growth raises blood pressure in adolescent boys who were thin at birth. Hypertension. 2003; 41, 451–456.Google Scholar
28. Singhal, A, Cole, TJ, Fewtrell, M, et al. Promotion of faster weight gain in infants born small for gestational age: is there an adverse effect on later blood pressure? Circulation. 2007; 115, 213–220.Google Scholar
29. Eriksson, JG, Forsen, TJ, Kajantie, E, Osmond, C, Barker, DJ. Childhood growth and hypertension in later life. Hypertension. 2007; 49, 1415–1421.Google Scholar
30. Eriksson, J, Forsen, T, Tuomilehto, J, Osmond, C, Barker, D. Fetal and childhood growth and hypertension in adult life. Hypertension. 2000; 36, 790–794.Google Scholar
31. Huang, RC, Burrows, S, Mori, TA, Oddy, WH, Beilin, LJ. Lifecourse adiposity and blood pressure between birth and 17 years old. Am J Hypertens. 2015; 28, 1056–1063.Google Scholar
32. Tauzin, L, Rossi, P, Grosse, C, et al. Increased systemic blood pressure and arterial stiffness in young adults born prematurely. J Dev Orig Health Dis. 2014; 5, 448–452.Google Scholar
33. Cruickshank, JK, Mzayek, F, Liu, L, et al. Origins of the “black/white” difference in blood pressure: roles of birth weight, postnatal growth, early blood pressure, and adolescent body size: the Bogalusa heart study. Circulation. 2005; 111, 1932–1937.Google Scholar
34. Cheung, YB, Low, L, Osmond, C, Barker, D, Karlberg, J. Fetal growth and early postnatal growth are related to blood pressure in adults. Hypertension. 2000; 36, 795–800.Google Scholar
35. Sterling, R, Checkley, W, Gilman, RH, et al. Beyond birth-weight: early growth and adolescent blood pressure in a Peruvian population. PeerJ. 2014; 2, e381.Google Scholar
36. Hardy, R, Wadsworth, ME, Langenberg, C, Kuh, D. Birthweight, childhood growth, and blood pressure at 43 years in a British birth cohort. Int J Epidemiol. 2004; 33, 121–129.Google Scholar
37. Adair, LS, Martorell, R, Stein, AD, et al. Size at birth, weight gain in infancy and childhood, and adult blood pressure in 5 low- and middle-income-country cohorts: when does weight gain matter? Am J Clin Nutr. 2009; 89, 1383–1392.Google Scholar
38. Adair, LS, Fall, CH, Osmond, C, et al. Associations of linear growth and relative weight gain during early life with adult health and human capital in countries of low and middle income: findings from five birth cohort studies. Lancet. 2013; 382, 525–534.Google Scholar
39. Kagura, J, Adair, LS, Munthali, RJ, Pettifor, JM, Norris, SA. Association between early life growth and blood pressure trajectories in Black South African children. Hypertension . 2016; 68, 1123–1131.Google Scholar
40. Law, CM. Fetal, infant, and childhood growth and adult blood pressure: a longitudinal study from birth to 22 years of age. Circulation. 2002; 105, 1088–1092.Google Scholar
41. Bansal, N, Ayoola, OO, Gemmell, I, et al. Effects of early growth on blood pressure of infants of British European and South Asian origin at one year of age: the Manchester children’s growth and vascular health study. J Hypertens. 2008; 26, 412–418.Google Scholar
42. Hemachandra, AH, Howards, PP, Furth, SL, Klebanoff, MA. Birth weight, postnatal growth, and risk for high blood pressure at 7 years of age: results from the Collaborative Perinatal Project. Pediatrics. 2007; 119, e1264–e1270.Google Scholar
43. Horta, BL, Barros, FC, Victora, CG, Cole, TJ. Early and late growth and blood pressure in adolescence. J Epidemiol Community Health. 2003; 57, 226–230.Google Scholar
44. Järvelin, MR, Sovio, U, King, V, et al. Early life factors and blood pressure at age 31 years in the 1966 northern Finland birth cohort. Hypertension. 2004; 44, 838–846.Google Scholar
45. Ben-Shlomo, Y, McCarthy, A, Hughes, R, et al. Immediate postnatal growth is associated with blood pressure in young adulthood: the Barry Caerphilly Growth Study. Hypertension. 2008; 52, 638–644.Google Scholar
46. Boyne, MS, Osmond, C, Fraser, RA, et al. Developmental origins of cardiovascular risk in Jamaican children: the Vulnerable Windows Cohort study. Br J Nutr. 2010; 104, 1026–1033.Google Scholar
47. Nowson, CA, Crozier, SR, Robinson, SM, et al. Association of early childhood abdominal circumference and weight gain with blood pressure at 36 months of age: secondary analysis of data from a prospective cohort study. BMJ Open. 2014; 4, e005412.Google Scholar
48. Antonisamy, B, Vasan, SK, Geethanjali, FS, et al. Weight gain and height growth during infancy, childhood, and adolescence as predictors of adult cardiovascular risk. J Pediatr. 2017; 180, 53–61.e53.Google Scholar
49. Jones, A, Charakida, M, Falaschetti, E, et al. Adipose and height growth through childhood and blood pressure status in a large prospective cohort study. Hypertension. 2012; 59, 919–925.Google Scholar
50. Holland, FJ, Stark, O, Ades, AE, Peckham, CS. Birth weight and body mass index in childhood, adolescence, and adulthood as predictors of blood pressure at age 36. J Epidemiol Community Health. 1993; 47, 432–435.Google Scholar
51. Schack-Nielsen, L, Holst, C, Sorensen, TI. Blood pressure in relation to relative weight at birth through childhood and youth in obese and non-obese adult men. Int J Obes Relat Metab Disord. 2002; 26, 1539–1546.Google Scholar
52. Perng, W, Rifas-Shiman, SL, Kramer, MS, et al. Early weight gain, linear growth, and mid-childhood blood pressure: a prospective study in project viva. Hypertension. 2016; 67, 301–308.Google Scholar
53. de Beer, M, Vrijkotte, TG, Fall, CH, et al. Associations of infant feeding and timing of weight gain and linear growth during early life with childhood blood pressure: findings from a prospective population based cohort study. PLoS One. 2016; 11, e0166281.Google Scholar
54. Cournil, A, Coly, AN, Diallo, A, Simondon, KB. Enhanced post-natal growth is associated with elevated blood pressure in young Senegalese adults. Int J Epidemiol. 2009; 38, 1401–1410.Google Scholar
55. Chiolero, A, Paradis, G, Bovet, P. Which period of growth is determinant for blood pressure? Hypertension. 2012; 60, e10; author reply e11.Google Scholar
56. Chiolero, A, Kaufman, JS, Paradis, G. Why adjustment for current weight can bias the estimate of the effect of birth weight on blood pressure: shedding light using causal graphs. J Hypertens. 2012; 30, 1042–1045.Google Scholar
57. Stein, AD, Zybert, PA, van der Pal-de Bruin, K, Lumey, LH. Exposure to famine during gestation, size at birth, and blood pressure at age 59 y: evidence from the Dutch Famine. Eur J Epidemiol. 2006; 21, 759–765.Google Scholar
58. Xin, X, Yao, J, Yang, F, Zhang, D. Famine exposure during early life and risk of hypertension in adulthood: A meta-analysis. Crit Rev Food Sci Nutr. 2017; 1–8 doi:10.1080/10408398.2017.1322551.Google Scholar
59. Martin, RM, Gunnell, D, Smith, GD. Breastfeeding in infancy and blood pressure in later life: systematic review and meta-analysis. Am J Epidemiol. 2005; 161, 15–26.Google Scholar
60. Fergusson, DM, McLeod, GF, Horwood, LJ. Breast feeding, infant growth, and body mass index at 30 and 35 years. Paediatr Perinat Epidemiol. 2014; 28, 545–552.Google Scholar
61. Geleijnse, JM, Hofman, A, Witteman, JCM, et al. Long-term Effects of neonatal sodium restriction on blood pressure. Hypertension. 1997; 29, 913–917.Google Scholar
62. Maslin, K, Grimshaw, K, Oliver, E, et al. Taste preference, food neophobia and nutritional intake in children consuming a cows’ milk exclusion diet: a prospective study. J Hum Nutr Diet. 2016; 29, 786–796.Google Scholar
63. Smriga, M, Kameishi, M, Torii, K. Brief exposure to NaCl during early postnatal development enhances adult intake of sweet and salty compounds. Neuroreport. 2002; 13, 2565–2569.Google Scholar
64. Brenna, JT, Varamini, B, Jensen, RG, et al. Docosahexaenoic and arachidonic acid concentrations in human breast milk worldwide. Am J Clin Nutr. 2007; 85, 1457–1464.Google Scholar
65. Forsyth, JS, Willatts, P, Agostoni, C, et al. Long chain polyunsaturated fatty acid supplementation in infant formula and blood pressure in later childhood: follow up of a randomised controlled trial. BMJ. 2003; 326, 953.Google Scholar
66. Decsi, T, Thiel, I, Koletzko, B. Essential fatty acids in full term infants fed breast milk or formula. Arch Dis Child Fetal Neonatal Ed. 1995; 72, F23–F28.Google Scholar
67. van Gijssel, RM, Braun, KV, Kiefte-de Jong, JC, et al. Associations between dietary fiber intake in infancy and cardiometabolic health at school age: the Generation R study. Nutrients. 2016; 8, 281–294.Google Scholar
68. Voortman, T, van den Hooven, EH, Tielemans, MJ, et al. Protein intake in early childhood and cardiometabolic health at school age: the Generation R Study. Eur J Nutr. 2016; 55, 2117–2127.Google Scholar
69. Bakker, H, Gaillard, R, Franco, OH, et al. Fetal and infant growth patterns and kidney function at school age. J Am Soc Nephrol. 2014; 25, 2607–2615.Google Scholar
70. Bacchetta, J, Harambat, J, Dubourg, L, et al. Both extrauterine and intrauterine growth restriction impair renal function in children born very preterm. Kidney Int. 2009; 76, 445–452.Google Scholar
71. Escribano, J, Luque, V, Ferre, N, et al. Increased protein intake augments kidney volume and function in healthy infants. Kidney Int. 2011; 79, 783–790.Google Scholar
72. Bakker, H, Kooijman, MN, van der Heijden, AJ, et al. Kidney size and function in a multi-ethnic population-based cohort of school-age children. Pediatr Nephrol. 2014; 29, 1589–1598.Google Scholar
73. Adibi, A, Adibi, I, Khosravi, P. Do kidney sizes in ultrasonography correlate to glomerular filtration rate in healthy children? Australas Radiol. 2007; 51, 555–559.Google Scholar
74. Ojeda, NB, Grigore, D, Alexander, BT. Intrauterine growth restriction: fetal programming of hypertension and kidney disease. Adv Chronic Kidney Dis. 2008; 15, 101–106.Google Scholar
75. Shen, Q, Xu, H, Wei, LM, Chen, J, Liu, HM. Intrauterine growth restriction and postnatal high-protein diet affect the kidneys in adult rats. Nutrition. 2011; 27, 364–371.Google Scholar
76. Vickers, MH, Breier, BH, Cutfield, WS, Hofman, PL, Gluckman, PD. Fetal origins of hyperphagia, obesity, and hypertension and postnatal amplification by hypercaloric nutrition. Am J Physiol Endocrinol Metab. 2000; 279, E83–E87.Google Scholar
77. Boubred, F, Delamaire, E, Buffat, C, et al. High protein intake in neonatal period induces glomerular hypertrophy and sclerosis in adulthood in rats born with IUGR. Pediatr Res. 2016; 79, 22–26.Google Scholar
78. Boubred, F, Daniel, L, Buffat, C, et al. Early postnatal overfeeding induces early chronic renal dysfunction in adult male rats. Am J Physiol Renal Physiol. 2009; 297, F943–F951.Google Scholar
79. Boubred, F, Buffat, C, Feuerstein, JM, et al. Effects of early postnatal hypernutrition on nephron number and long-term renal function and structure in rats. Am J Physiol Renal Physiol. 2007; 293, F1944–F1949.Google Scholar
80. Yim, HE, Ha, KS, Bae, IS, et al. Overweight, hypertension and renal dysfunction in adulthood of neonatally overfed rats. J Nutr Biochem. 2013; 24, 1324–1333.Google Scholar
81. Yim, HE, Yoo, KH, Bae, IS, Hong, YS, Lee, JW. Postnatal early overnutrition causes long-term renal decline in aging male rats. Pediatr Res. 2014; 75, 259–265.Google Scholar
82. Alcazar, MA, Boehler, E, Rother, E, et al. Early postnatal hyperalimentation impairs renal function via SOCS-3 mediated renal postreceptor leptin resistance. Endocrinology. 2012; 153, 1397–1410.Google Scholar
83. Habbout, A, Li, N, Rochette, L, Vergely, C. Postnatal overfeeding in rodents by litter size reduction induces major short- and long-term pathophysiological consequences. J Nutr. 2013; 143, 553–562.Google Scholar
84. Alejandre Alcazar, MA, Boehler, E, Amann, K, et al. Persistent changes within the intrinsic kidney-associated NPY system and tubular function by litter size reduction. Nephrol Dial Transplant. 2011; 26, 2453–2465.Google Scholar
85. Hoppe, CC, Evans, RG, Moritz, KM, et al. Combined prenatal and postnatal protein restriction influences adult kidney structure, function, and arterial pressure. Am J Physiol Regul Integr Comp Physiol. 2007; 292, R462–R469.Google Scholar
86. Petry, CJ, Jennings, BJ, James, LA, Hales, CN, Ozanne, SE. Suckling a protein-restricted rat dam leads to diminished albuminuria in her male offspring in adult life: a longitudinal study. BMC Nephrol. 2006; 7, 14.Google Scholar
87. Tarry-Adkins, JL, Joles, JA, Chen, JH, et al. Protein restriction in lactation confers nephroprotective effects in the male rat and is associated with increased antioxidant expression. Am J Physiol Regul Integr Comp Physiol. 2007; 293, R1259–R1266.Google Scholar
88. Wlodek, ME, Westcott, K, Siebel, AL, Owens, JA, Moritz, KM. Growth restriction before or after birth reduces nephron number and increases blood pressure in male rats. Kidney Int. 2008; 74, 187–195.Google Scholar
89. Wlodek, ME, Mibus, A, Tan, A, et al. Normal lactational environment restores nephron endowment and prevents hypertension after placental restriction in the rat. J Am Soc Nephrol. 2007; 18, 1688–1696.Google Scholar
90. Peter, RF, Gugusheff, J, Wooldridge, AL, Gatford, KL, Muhlhausler, BS. Placental restriction in multi-fetal pregnancies and between-twin differences in size at birth alter neonatal feeding behaviour in the sheep. J Dev Orig Health Dis. 2017; 8, 357–369.Google Scholar
91. Padia, SH, Carey, RM. AT2 receptors: beneficial counter-regulatory role in cardiovascular and renal function. Pflugers Arch. 2013; 465, 99–110.Google Scholar
92. Yim, HE, Ha, KS, Bae, IS, et al. Postnatal early overnutrition dysregulates the intrarenal renin-angiotensin system and extracellular matrix-linked molecules in juvenile male rats. J Nutr Biochem. 2012; 23, 937–945.Google Scholar
93. Granado, M, Amor, S, Fernandez, N, et al. Effects of early overnutrition on the renal response to Ang II and expression of RAAS components in rat renal tissue. Nutr Metab Cardiovasc Dis. 2017; 27, 930–937.Google Scholar
94. Torretti, J. Sympathetic control of renin release. Annu Rev Pharmacol Toxicol. 1982; 22, 167–192.Google Scholar
95. Sherman, RC, Langley-Evans, SC. Early administration of angiotensin-converting enzyme inhibitor captopril, prevents the development of hypertension programmed by intrauterine exposure to a maternal low-protein diet in the rat. Clin Sci. 1998; 94, 373–381.Google Scholar
96. Sherman, RC, Langley-Evans, SC. Antihypertensive treatment in early postnatal life modulates prenatal dietary influences upon blood pressure in the rat. Clin Sci. 2000; 98, 269–275.Google Scholar
97. Yim, HE, Yoo, KH, Bae, IS, Hong, YS. Early treatment with enalapril and later renal injury in programmed obese adult rats. J Cell Physiol. 2017; 232, 447–455.Google Scholar
98. Simeoni, U, Ligi, I, Buffat, C, Boubred, F. Adverse consequences of accelerated neonatal growth: cardiovascular and renal issues. Pediatr Nephrol. 2011; 26, 493–508.Google Scholar
99. Dotsch, J, Plank, C, Amann, K, Ingelfinger, J. The implications of fetal programming of glomerular number and renal function. J Mol Med. 2009; 87, 841–848.Google Scholar
100. Woods, LL, Ingelfinger, JR, Nyengaard, JR, Rasch, R. Maternal protein restriction suppresses the newborn renin-angiotensin system and programs adult hypertension in rats. Pediatr Res. 2001; 49, 460–467.Google Scholar
101. Correia-Melo, C, Hewitt, G, Passos, JF. Telomeres, oxidative stress and inflammatory factors: partners in cellular senescence? Longev Healthspan. 2014; 3, 1.Google Scholar
102. Sturmlechner, I, Durik, M, Sieben, CJ, Baker, DJ, van Deursen, JM. Cellular senescence in renal ageing and disease. Nat Rev Nephrol. 2017; 13, 77–89.Google Scholar
103. Walsh, ME, Shi, Y, Van Remmen, H. The effects of dietary restriction on oxidative stress in rodents. Free Radic Biol Med. 2014; 66, 88–99.Google Scholar
104. Samocha-Bonet, D, Campbell, LV, Mori, TA, et al. Overfeeding reduces insulin sensitivity and increases oxidative stress, without altering markers of mitochondrial content and function in humans. PLoS One. 2012; 7, e36320.Google Scholar
105. Jennings, BJ, Ozanne, SE, Dorling, MW, Hales, CN. Early growth determines longevity in male rats and may be related to telomere shortening in the kidney. FEBS Lett. 1999; 448, 4–8.Google Scholar
106. Tarry-Adkins, JL, Ozanne, SE, Norden, A, Cherif, H, Hales, CN. Lower antioxidant capacity and elevated p53 and p21 may be a link between gender disparity in renal telomere shortening, albuminuria, and longevity. Am J Physiol Renal Physiol. 2006; 290, F509–F516.Google Scholar
107. Wolf, G, Chen, S, Han, DC, Ziyadeh, FN. Leptin and renal disease. Am J Kidney Dis. 2002; 39, 1–11.Google Scholar
108. Beltowski, J, Jamroz-Wisniewska, A, Borkowska, E, Wojcicka, G. Up-regulation of renal Na+, K+-ATPase: the possible novel mechanism of leptin-induced hypertension. Pol J Pharmacol. 2004; 56, 213–222.Google Scholar
109. Bischoff, A, Michel, MC. Renal effects of neuropeptide Y. Pflugers Arch. 1998; 435, 443–453.Google Scholar
110. Leite, RD, Kraemer-Aguiar, LG, Boa, BC, et al. Muscle endothelial-dependent microvascular dysfunction in adulthood due to early postnatal overnutrition. Microvasc Res. 2012; 84, 94–98.Google Scholar
111. Coatmellec-Taglioni, G, Dausse, JP, Giudicelli, Y, Ribiere, C. Sexual dimorphism in cafeteria diet-induced hypertension is associated with gender-related difference in renal leptin receptor down-regulation. J Pharmacol Exp Ther. 2003; 305, 362–367.Google Scholar
112. Emanuel, I, Filakti, H, Alberman, E, Evans, SJ. Intergenerational studies of human birthweight from the 1958 birth cohort. 1. Evidence for a multigenerational effect. Br J Obstet Gynaecol. 1992; 99, 67–74.Google Scholar
113. Unterberger, A, Szyf, M, Nathanielsz, PW, Cox, LA. Organ and gestational age effects of maternal nutrient restriction on global methylation in fetal baboons. J Med Primatol. 2009; 38, 219–227.Google Scholar
114. Mouillet, JF, Chu, T, Hubel, CA, et al. The levels of hypoxia-regulated microRNAs in plasma of pregnant women with fetal growth restriction. Placenta. 2010; 31, 781–784.Google Scholar
115. Huang, L, Shen, Z, Xu, Q, et al. Increased levels of microRNA-424 are associated with the pathogenesis of fetal growth restriction. Placenta. 2013; 34, 624–627.Google Scholar
116. Pham, TD, MacLennan, NK, Chiu, CT, et al. Uteroplacental insufficiency increases apoptosis and alters p53 gene methylation in the full-term IUGR rat kidney. Am J Physiol Regul Integr Comp Physiol. 2003; 285, R962–R970.Google Scholar
117. Bogdarina, I, Welham, S, King, PJ, Burns, SP, Clark, AJ. Epigenetic modification of the renin-angiotensin system in the fetal programming of hypertension. Circ Res. 2007; 100, 520–526.Google Scholar
118. Rodriguez, MM, Gomez, AH, Abitbol, CL, et al. Histomorphometric analysis of postnatal glomerulogenesis in extremely preterm infants. Pediatr Dev Pathol. 2004; 7, 17–25.Google Scholar
119. Martin, RM, McCarthy, A, Smith, GD, Davies, DP, Ben-Shlomo, Y. Infant nutrition and blood pressure in early adulthood: the Barry Caerphilly Growth study. Am J Clin Nutr. 2003; 77, 1489–1497.Google Scholar
120. Ekelund, U, Ong, KK, Linne, Y, et al. Association of weight gain in infancy and early childhood with metabolic risk in young adults. J Clin Endocrinol Metab. 2007; 92, 98–103.Google Scholar
Figure 0

Fig. 1 Flow chart of identified, included and excluded studies.

Figure 1

Table 1 Summary of the main epidemiological findings in human studies about associations between growth patterns and renal outcomes

Figure 2

Table 2 Summary of the main findings in animal studies about early postnatal nutrition and renal outcome later in life