Developmental programming of a reduced nephron endowment: more than just a baby's birth weight

Moritz, Karen M.; Singh, Reetu R.; Probyn, Megan Elizabeth; Denton, Kate M.

doi:10.1152/ajprenal.00049.2008

Cited by 95 publications

(96 citation statements)

References 117 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For example, short-term prenatal glucocorticoid exposure can result in a reduced nephron endowment without changes in kidney weight at birth. 30 Recently, we found no change in kidney weight but an 11% reduction in nephron number in response to ethanol exposure during the latter half of gestation in an ovine model. 9 In the study presented here, we identified a reduction in kidney weight in male ethanol-exposed offspring at PN30 but no reduction in kidney weight in ethanol-exposed female offspring, even although there was a reduction in nephron number.…”

Section: Discussionmentioning

confidence: 83%

Prenatal Exposure to Alcohol Reduces Nephron Number and Raises Blood Pressure in Progeny

Gray

Denton²,

Cullen‐McEwen³

et al. 2010

Journal of the American Society of Nephrology

Self Cite

115

133

View full text Add to dashboard Cite

Prenatal ethanol exposure is teratogenic, but the effects of ethanol on kidney development and the health of offspring are incompletely understood. Our objective was to investigate the effects of acute ethanol exposure during pregnancy on nephron endowment, mean arterial pressure, and renal function in offspring. We administered ethanol or saline by gavage to pregnant Sprague-Dawley rats on embryonic days 13.5 and 14.5. At 1 month of age, the nephron number was 15% lower and 10% lower in ethanol-exposed males and females, respectively, compared with controls. Mean arterial pressure, measured in conscious animals via indwelling tail-artery catheter, was 10% higher in both ethanolexposed males and females compared with controls. GFR was 20% higher in ethanol-exposed males but 15% lower in ethanol-exposed females; moreover, males had increased proteinuria compared with controls. Furthermore, embryonic kidneys cultured in the presence of ethanol for 48 hours had 15% fewer ureteric branch points and tips than kidneys cultured in control media. Taken together, these data demonstrate that acute prenatal ethanol exposure reduces the number of nephrons, possibly as a result of inhibited ureteric branching morphogenesis, and that these changes affect adult cardiovascular and renal function. 21: 189121: -190221: , 201021: . doi: 10.1681 In Western communities, alcohol (ethanol) consumption by pregnant women is a relatively common occurrence. 1 Some women, while reducing their daily alcohol consumption, partake in episodes of acute (binge) drinking while pregnant. 2 Whereas in most countries guidelines generally recommend that pregnant women abstain from alcohol consumption, many women still consume alcohol in the early stages of their pregnancy. This is of clinical importance because many pregnancies are unconfirmed until the end of the first trimester. 3 Whereas strong evidence suggests chronic consumption of high doses of ethanol are teratogenic, the effects of acute ethanol exposure on the fetus are less well understood. Animal studies have demonstrated that acute ethanol exposure is associated with neuroapoptosis, reduced brain growth, and pulmonary alveolar dysfunction. 4 -6 However, the effects of ethanol exposure during pregnancy on kidney development and long-term renal and cardiovascular function are yet to be thoroughly explored. J Am Soc NephrolRats chronically exposed to ethanol during pregnancy have a reduced ability to concentrate urine at 90 days of age, and renal DNA and protein content is reduced at 7 days of age. 7,8 Recently, we have shown that repeated maternal ethanol administration during the peak period of nephrogenesis in fetal sheep results in an 11% lower nephron endow-

show abstract

Section: Discussionmentioning

confidence: 83%

Prenatal Exposure to Alcohol Reduces Nephron Number and Raises Blood Pressure in Progeny

Gray

Denton²,

Cullen‐McEwen³

et al. 2010

Journal of the American Society of Nephrology

Self Cite

115

133

View full text Add to dashboard Cite

show abstract

“…It might be expected that this was due to comorbidity, but this was not the case. Another possible explanation is that the low nephron mass associated with low birth weight (18) resulted in reduced residual renal function, a recognized risk factor for mortality on dialysis (6); however, the causes of death were varied, and there is no obvious explanation for this finding.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Outcome of Infants with Severe Chronic Kidney Disease

Mekahli

Shaw

Ledermann

et al. 2010

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Background and objectives: In 2000, we reported the outcome of 101 children with a GFR <20 ml/min per 1.73 m 2 at 0.3 yr of age (range 0.0 to 1.5 yr). Long-term data on such young children are scarce.Design, setting, participants, & measurements: Mortality, treatment modalities, and growth were reanalyzed 9.9 yr later. Results: Of the 101 patients, 28 died and three were lost to follow-up during 13.90 yr (range 0.03 to 22.90 yr). One-, 2-, 5-, 10-, 15-, 20-, and 22-yr survivals were 87, 81, 77, 75, 73, 72, and 64%, respectively. Fifty-one children had comorbidities. Sixty-six percent were tube fed for 1.7 yr (range 0.1 to 6.9 yr), 37% had a gastrostomy, and 13% had a Nissen fundoplication. Mean height SD score (SD) was ؊0.42 (2.33) at birth (n ‫؍‬ 40), ؊2.07 (1.34) at 0.5 (n ‫؍‬ 62), ؊1.93 (1.38) at 1 (n ‫؍‬ 72), ؊1.14 (1.14) at 5 (n ‫؍‬ 67), ؊1.04 (1.15) at 10 (n ‫؍‬ 62), ؊1.84 (1.32) at 15 (n ‫؍‬ 40), and ؊1.68 (1.52) at age >18 yr (n ‫؍‬ 32). Comorbidities adversely influenced growth (P < 0.01) and final height (P ‫؍‬ 0.02): Mean height SD score (SD) was ؊1.16 (1.38) in otherwise normal adults.Conclusions: Growth and final height in infants with severe chronic kidney disease are influenced by comorbidity. Intensive feeding and early transplantation resulted in a mean adult height within the normal range in patients without comorbidities. Overall mortality is comparable to that of older children.Clin J Am Soc Nephrol

show abstract

“…14 Another example of permanent alteration induced by developmental plasticity is provided by the observation that adult nephron numbers are reduced both in humans and in animals exposed to suboptimal uterine environment that develop hypertension in adult life. [15][16][17][18] This might represent the consequence of a biological trade-off to spare energy in response to in utero nutrient deprivation, having immediate but no long-term adaptive value.…”

Section: The Mechanisms Of Programmingmentioning

confidence: 99%

Effect of intrauterine growth retardation on liver and long-term metabolic risk

Cianfarani

Agostoni

Bedogni³

et al. 2012

Int J Obes

View full text Add to dashboard Cite

Intrauterine growth retardation predisposes toward long-term morbidity from type 2 diabetes and cardiovascular disease. To explain this association, the concept of programming was introduced to indicate a process whereby a stimulus or insult at a critical period of development has lasting or lifelong consequences on key endocrine and metabolic pathways. Subtle changes in cell composition of tissues, induced by suboptimal conditions in utero, can influence postnatal physiological functions. There is increasing evidence, suggesting that liver may represent one of the candidate organs targeted by programming, undergoing structural, functional and epigenetic changes following exposure to an unfavorable intrauterine environment. The aim of this review is to provide insights into the molecular mechanisms underlying liver programming that contribute to increase the cardiometabolic risk in subjects with intrauterine growth restriction.

show abstract

Developmental programming of a reduced nephron endowment: more than just a baby's birth weight

Abstract: Moritz KM, Singh RR, Probyn ME, Denton KM. Developmental programming of a reduced nephron endowment: more than just a baby's birth weight.

Cited by 95 publications

References 117 publications

Prenatal Exposure to Alcohol Reduces Nephron Number and Raises Blood Pressure in Progeny

Prenatal Exposure to Alcohol Reduces Nephron Number and Raises Blood Pressure in Progeny

Long-Term Outcome of Infants with Severe Chronic Kidney Disease

Effect of intrauterine growth retardation on liver and long-term metabolic risk

Contact Info

Product

Resources

About