Fetal programming of renal function

Dötsch, Jörg; Plank, Christian; Amann, Kerstin

doi:10.1007/s00467-011-1781-5

Cited by 34 publications

(18 citation statements)

References 69 publications

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“…There are several proposed mechanisms that may contribute to fetal renal underdevelopment [28]. Changes in the growth factors in the uterus can clearly play an important role.…”

Section: Discussionmentioning

confidence: 99%

“…Proteinuria is a biomarker reflecting progressive renal dysfunction [52]. It has been suggested that reduced nephron number at birth can lead to the adaptation of glomerular hypertrophy and hyperfiltration in order to maintain sufficient renal function [26], [28], [39], [53]. Prolonged hyperfiltration can in turn lead to hyperfiltration injury in the long term, resulting in structural injury and functional deterioration in adulthood [26].…”

Section: Discussionmentioning

confidence: 99%

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The Impact of Maternal Cigarette Smoke Exposure in a Rodent Model on Renal Development in the Offspring

et al. 2014

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This study aimed to investigate whether maternal cigarette smoke exposure can disrupt fetal kidney development by changing the expression of growth and transcription factors essential for renal development, and thereafter predispose the offspring to chronic kidney disease later in life. Female Balb/c mice (6 weeks) were exposed either to cigarette smoke or air under identical conditions, 6 weeks prior to mating, during gestation and during lactation. Male offspring were sacrificed at three time points, postnatal day (P)1, P20 (weaning age), and 13 weeks (mature age). Blood, urine, and kidneys were collected for analysis. At P1, the developmental genes fibroblast growth factor 2, glial cell-line derived neurotrophic factor and paired box 2 were upregulated at mRNA and protein levels; whilst fibroblast growth factor (FGF) 7 and FGF10 were downregulated. At P20, mRNA expression of FGF2, FGF10 and Wingless-type 4 was upregulated by maternal smoke exposure. These changes were normalised in adulthood. Nephron development was delayed, with fewer nephron numbers from P1 persisted to adulthood; while glomerular volume was increased at P20 but reduced in adulthood. Pro-inflammatory marker monocyte chemoatractant protein 1 (MCP1) was increased in the kidney by maternal smoke exposure. These changes were accompanied by an increased albumin/creatinine ratio in adulthood, suggesting reduced renal dysfunction. In conclusion maternal cigarette smoke exposure prior to and during pregnancy, as well as lactation leads to significant renal underdevelopment and functional abnormalities in adulthood. This study confirms the hypothesis that maternal smoking predisposes offspring to chronic kidney disorders.

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“…There are several proposed mechanisms that may contribute to fetal renal underdevelopment [28]. Changes in the growth factors in the uterus can clearly play an important role.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Impact of Maternal Cigarette Smoke Exposure in a Rodent Model on Renal Development in the Offspring

et al. 2014

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“…Because the estimated prevalence of obesity in women of reproductive age in the United States is 31.8%, and rates are similar in other developed countries, including the United Kingdom and Australia (19), maternal obesity may set forth the above-described pathophysiologic mechanisms from early in prenatal life (20). This concept that adverse conditions during early life increase the susceptibility to chronic diseases in adulthood underpins the theory of the developmental origins of health and disease (21). Fetal programming has been implicated in the development of conditions such as cardiovascular disease, hypertension, T2D, obesity, and CKD (22).…”

Section: Fetal Programming Maternal Transmission Of Disease and Epimentioning

confidence: 99%

DNA methylation and the potential role of demethylating agents in prevention of progressive chronic kidney disease

et al. 2018

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Chronic kidney disease (CKD) is a global epidemic, and its major risk factors include obesity and type 2 diabetes. Obesity not only promotes metabolic dysregulation and the development of diabetic kidney disease but also may independently lead to CKD by a variety of mechanisms, including endocrine and metabolic dysfunction, inflammation, oxidative stress, altered renal hemodynamics, and lipotoxicity. Deleterious renal effects of obesity can also be transmitted from one generation to the next, and it is increasingly recognized that offspring of obese mothers are predisposed to CKD. Epigenetic modifications are changes that regulate gene expression without altering the DNA sequence. Of these, DNA methylation is the most studied. Epigenetic imprints, particularly DNA methylation, are laid down during critical periods of fetal development, and they may provide a mechanism by which maternal-fetal transmission of chronic disease occurs. Our current review explores the evidence for the role of DNA methylation in the development of CKD, diabetic kidney disease, diabetes, and obesity. DNA methylation has been implicated in renal fibrosis-the final pathophysiologic pathway in the development of end-stage kidney disease-which supports the notion that demethylating agents may play a potential therapeutic role in preventing development and progression of CKD.-Larkin, B. P., Glastras, S. J., Chen, H., Pollock, C. A., Saad, S. DNA methylation and the potential role of demethylating agents in prevention of progressive chronic kidney disease.

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“…In addition, there is an almost tenfold variation in normal nephron numbers, ranging from a little over 200,000 to over 2.5 million nephrons per kidney [3]. Some of this variation may be explained by genetic differences, and many environmental factors may influence final nephron numbers as well [8]. …”

Section: Nephron Numbersmentioning

confidence: 99%

Safety in glomerular numbers

Schreuder

2012

Pediatr Nephrol

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A low nephron number is, according to Brenner’s hyperfiltration hypothesis, associated with hypertension, glomerular damage and proteinuria, and starts a vicious cycle that ends in renal failure over the long term. Nephron endowment is set during foetal life, and there is no formation of nephrons after 34–36 weeks of gestation, indicating that many factors before that time-point may have an impact on kidney development and reduce nephron numbers. Such factors include maternal malnutrition, stress, diseases, such as diabetes, uteroplacental insufficiency, maternal and neonatal drugs and premature birth. However, other congenital anomalies, such as renal hypoplasia, unilateral renal agenesis or multicystic dysplastic kidney, may also lead to a reduced nephron endowment, with an increased risk for hypertension, renal dysfunction and the need for renal replacement therapy. This review focusses on the causes and consequences of a low nephron endowment and will illustrate why there is safety in glomerular numbers.•

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Fetal programming of renal function

Cited by 34 publications

References 69 publications

The Impact of Maternal Cigarette Smoke Exposure in a Rodent Model on Renal Development in the Offspring

The Impact of Maternal Cigarette Smoke Exposure in a Rodent Model on Renal Development in the Offspring

DNA methylation and the potential role of demethylating agents in prevention of progressive chronic kidney disease

Safety in glomerular numbers

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