Podocyte endowment and the impact of adult body size on kidney health

Author(s):  
Luise Anne Cullen-McEwen ◽  
James van der Wolde ◽  
Kotaro Haruhara ◽  
Leon Tribolet ◽  
John Dowling ◽  
...  

Low birth weight is a risk factor for chronic kidney disease (CKD), while adult podocyte depletion is a key event in the pathogenesis of glomerulosclerosis. However, whether low birth weight due to poor maternal nutrition is associated with low podocyte endowment and glomerulosclerosis in later life is not known. Female Sprague-Dawley rats were fed a normal (NPD, 20%) or low (LPD, 8%) protein diet from 3 weeks before mating until postnatal day 21 (PN21), when kidneys from some male offspring were taken for quantitation of podocyte number and density in whole glomeruli using immunolabeling, tissue clearing and confocal microscopy. Remaining offspring were fed a normal or high fat diet until 6 months to induce catch-up growth and excessive weight gain, respectively. At PN21, podocyte number per glomerulus was 15% lower in low birth weight (LPD) than normal birthweight (NPD) offspring, with this deficit greater in outer glomeruli. Surprisingly, podocyte number in LPD offspring increased in outer glomeruli between PN21 and 6 months, although an overall 9% podocyte deficit persisted. Postnatal fat feeding to LPD offspring did not alter podometric indices or result in glomerular pathology at 6 months, whereas fat feeding in NPD offspring was associated with far greater body and fat mass as well as podocyte loss, reduced podocyte density, albuminuria and glomerulosclerosis. This is the first report that maternal diet can influence podocyte endowment. Our findings provide new insights into the impact of low birth weight, podocyte endowment and postnatal weight on podometrics and renal health in adulthood.

Author(s):  
Alexandra Paul ◽  
Rebecca Deans ◽  
Russell Viner ◽  
Sarah M. Creighton

Abstract Introduction: Premature infants, especially very low birth weight infants, and fetal growth restriction are a challenge for healthcare professionals alike owing to the consequences of these conditions. Objective: To provide information for gynecologists, pediatricians and neonatologists to identify correct outcome expectations to help them plan their preventive and therapeutic actions. Searches were made on the MEDLINE database. Results: According to several follow-up studies, there is an increasing evidence for a link between early life exposures (prenatal and postnatal) and long-term outcomes. An adverse in utero environment will induce fetal reprogramming of neuroendocrine axes with permanent alterations of the physiology and metabolism of various body structures and functioning of neuroendocrine axes in later life, leading to a variety of different conditions, such as persistence of neurodevelopmental disability, changes in growth pattern, in body metabolism, in pubertal development, lower educational achievement and even psychological disturbances with possible alterations of sexual behavior in female adolescents and young adults. In addition, short-term transitory consequences can be also present, such as anomalies in genital appearance. Conclusions: Outcome studies on the impact that prematurity, low birth weight and intrauterine growth restriction have on pubertal development, sexuality and fertility are still scarce. Long-term outcomes of small for gestational age or preterm adolescents are complex and multifactorial, with interactions between genetic and environmental influences involving different pathways of adaptive responses during crucial phases of prenatal growth.


2009 ◽  
Vol 87 (3) ◽  
pp. 161-179 ◽  
Author(s):  
Caroline Le Clair ◽  
Tina Abbi ◽  
Heather Sandhu ◽  
Paramjit S. Tappia

Epidemiological, clinical, and experimental observations have led to the hypothesis that the risk of developing chronic diseases in adulthood is influenced not only by genetic and adult lifestyle factors, but also by environmental factors during early life. Low birth weight, a marker of intrauterine stress, has been linked to predisposition to cardiovascular disease (CVD) and diabetes. The compelling animal evidence and significant human data to support this conclusion are reviewed. Specifically, the review discusses the role of maternal nutrition before and during pregnancy, placental insufficiencies and epigenetic changes in the increased predisposition to diabetes and CVD in adult life. The impact of low birth weight and catch-up growth as they pertain to risk of disease in adult life is also discussed. In addition, adult disease risk in the overnourished fetus is also mentioned. Reference is made to some of the mechanisms of the induction of diabetes and CVD phenotype. It is proposed that fetal nutrition, growth and development through efficient maternal nutrition before and during pregnancy could constitute the basis for nutritional strategies for the primary prevention of diabetes and CVD.


2019 ◽  
Vol 160 (32) ◽  
pp. 1270-1278
Author(s):  
Réka Turai ◽  
Márton Ferenc Schandl ◽  
Timea Dergez ◽  
Réka Anna Vass ◽  
Tímea Kvárik ◽  
...  

Abstract: Introduction: During recent decades, the perinatal mortality of extremely low-birth weight infants has decreased. An important task is to recognize complications of prematurity. Aim: We made an attempt to explore the relationship between complications of prematurity and neonatal hyperglycemia. Method: From 1 January 2014 to 31 December 2017, 188 infants with birth weight below 1000 g were admitted. For each infant, the frequencies of hyperglycemia (blood glucose >8.5 mmol/l), retinopathy of prematurity, intraventricular hemorrhage, and bronchopulmonary dysplasia were determined. Animal studies were performed in Sprague Dawley rats. Hyperglycemia was achieved by intraperitoneal injection of streptozotocin (100 mg/kg). On the 7th day of life, aorta sections were prepared and stained with hematoxylin eosin. Wall thickness was measured using QCapture Pro 7 image analysis software. Results: The mean ± SD gestational age and birth weight were 27.1 ± 2.2 weeks and 814.9 ± 151.9 g; 33 infants (17.5%) died. Hyperglycemia was confirmed in 62 cases (32.9%), and insulin treatment was given to 43 infants (22.8%). The gestational age and birth weight of the hyperglycemic infants were significantly lower (p<0.001), the incidence of severe retinopathy (p = 0.012) and the mortality of insulin-treated patients were higher (p = 0.02) than in normoglycemic infants. Among survivors (n = 155), we found by logistic regression analysis that hyperglycemia was a risk factor for severe retinopathy (p<0.001). In the rat model, neonatal hyperglycemia caused significant thickening of the aortic wall. Conclusion: Our studies indicate that hyperglycemia is common in extremely low birth-weight infants. Monitoring of these infants for retinopathy of prematurity, kidney dysfunction, and hypertension is recommended. Orv Hetil. 2019; 160(32): 1270–1278.


2018 ◽  
Vol 39 (2_suppl) ◽  
pp. S54-S59 ◽  
Author(s):  
David C. Clark

Background: One in 4 children globally is stunted. Stunting is associated with reduced cognitive development, reduced productivity, and chronic disease in later life. Objective: To explore the association between maternal diet during pregnancy and low birth weight, which increases the risk of stunting. Methods: Current literature pertaining to maternal diet and low birth weight was reviewed. Results: Low birth weight and small for gestational age are risk factors for stunting. Dietary pattern studies show an association between moderate dairy protein intake and increased birth weight and reduced risk of low birth weight. Protein-to-carbohydrate ratios are important factors in relation to gestational weight gain and fetal programming. There is evidence suggesting that whey protein could play a role in fetal lean body mass and reduced risk of low birth weight. Conclusions: Maternal diet is associated with birth weight.


2010 ◽  
Vol 0 (0) ◽  
Author(s):  
Honorina de Almeida ◽  
Sonia I. Venancio ◽  
Maria Teresa C. Sanches ◽  
Daisuke Onuki

2020 ◽  
pp. 1-25
Author(s):  
Yidi Wang ◽  
Bradley A. Feltham ◽  
Michael N. A. Eskin ◽  
Miyoung Suh

Abstract Maternal nutrition status plays an important role in the development of fetal alcohol spectrum disorders (FASD), but its direct evidence is lacking. This study compared a standard chow with a semi-purified energy dense (E-dense) diet on birth and metabolic outcomes in rats after ethanol (EtOH) consumption during pregnancy. Pregnant Sprague-Dawley rats were randomized into four groups: chow (n=6), chow+EtOH (20% v/v) (n=7), E-dense (n=6), and E-dense+EtOH (n=8). Birth outcomes including litter size, body and organ weights were collected. Metabolic parameters were measured in dams and pups at postnatal day (PD) 7. Maternal EtOH consumption decreased body weights (p <0.0001) and litter sizes (p <0.05) in chow-fed dams. At PD7, pups born to dams fed E-dense diet had higher body (p <0.002) and liver weights (p <0.0001). These pups also had higher plasma total cholesterol (p <0.0001), triacyclglycerol (p <0.003) and alanine aminotransferase (p <0.03) compared to those from chow-fed dams. Dams fed E-dense diet had higher plasma total- (p <0.0001) and HDL-cholesterol (p <0.0001) and lower glucose (p <0.0001). EtOH increased total cholesterol (p <0.03) and glucose (p <0.05) only in dams fed the E-dense diet. Maternal exposure to E-dense diet attenuated prenatal EtOH-induced weight loss and produced different metabolic outcomes in both dams and pups. While the long-lasting effects of these outcomes are unknown, this study highlights the importance of maternal diet quality for maternal health and infant growth, and suggests that maternal nutrition intervention may be a potential target for alleviating FASD.


2021 ◽  
pp. 1-8
Author(s):  
S. Melker Hagsäter ◽  
Robert Pettersson ◽  
Axel Holmäng ◽  
Elias Eriksson

Abstract Objective: Whereas numerous experimental and clinical studies suggest a complex involvement of serotonin in the regulation of anxiety, it remains to be clarified if the dominating impact of this transmitter is best described as anxiety-reducing or anxiety-promoting. The aim of this study was to assess the impact of serotonin depletion on acquisition, consolidation, and expression of conditioned fear. Methods: Male Sprague–Dawley rats were exposed to foot shocks as unconditioned stimulus and assessed with respect to freezing behaviour when re-subjected to context. Serotonin depletion was achieved by administration of a serotonin synthesis inhibitor, para-chlorophenylalanine (PCPA) (300 mg/kg daily × 3), (i) throughout the period from (and including) acquisition to (and including) expression, (ii) during acquisition but not expression, (iii) after acquisition only, and (iv) during expression only. Results: The time spent freezing was significantly reduced in animals that were serotonin-depleted during the entire period from (and including) acquisition to (and including) expression, as well as in those being serotonin-depleted during either acquisition only or expression only. In contrast, PCPA administrated immediately after acquisition, that is during memory consolidation, did not impact the expression of conditioned fear. Conclusion: Intact serotonergic neurotransmission is important for both acquisition and expression of context-conditioned fear.


Author(s):  
Mouctar Sow ◽  
Myriam De Spiegelaere ◽  
Marie-France Raynault

Variations in social policy between countries provide opportunities to assess the impact of these policies on health inequities. This study compares the risk of low birth weight in Brussels and Montreal, according to household composition, and discusses the impact of income support policies. For each context, we estimated the impact of income support policies on the extent of poverty of welfare recipients, using the model family method. Based on the differences found, we tested hypotheses on the association between low birth weight and household composition, using administrative data from the birth register and social security in each region. The extent of poverty of welfare families differs according to household composition. In Quebec, the combination of low welfare benefits and larger family allowances widens the gap between households with children and those without children. The risk of LBW also differs between these two contexts according to the number of children. Compared to children born into large welfare families, first-born children are more at risk in Montreal than in Brussels. In addition to the usual comparative studies on the topic, our study highlights the importance of an evaluative perspective that considers the combination of different types of income support measures to better identify the most vulnerable households.


Author(s):  
Tamara van Donge ◽  
Anne Smits ◽  
John van den Anker ◽  
Karel Allegaert

Background: Disentangling renal adverse drug reactions from confounders remains a major challenge to assess causality and severity in neonates, with additional limitations related to the available tools (modified Kidney Disease Improving Global Outcome, or Division of Microbiology and Infectious Diseases pediatric toxicity table). Vancomycin and amikacin are nephrotoxic while still often prescribed in neonates. We selected these compounds to assess their impact on creatinine dynamics as a sensitive tool to detect a renal impairment signal. Methods: A recently developed dynamical model that characterized serum creatinine concentrations of 217 extremely low birth weight (<1000 g, ELBW) neonates (4036 observations) was enhanced with data on vancomycin and/or amikacin exposure to identify a potential effect of antibiotic exposure by nonlinear mixed-effects modelling. Results: Seventy-seven percent of ELBW patients were exposed to either vancomycin or amikacin. Antibiotic exposure resulted in a modest increase in serum creatinine and a transient decrease in creatinine clearance. The serum creatinine increase was dependent on gestational age, illustrated by a decrease with 56% in difference in serum creatinine between a 24 or 32-week old neonate, when exposed in the 3rd week after birth. Conclusions: A previously described model was used to explore and quantify the impact of amikacin or vancomycin exposure on creatinine dynamics. Such tools serve to explore minor changes, or compare minor differences between treatment modalities.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Duah Dwomoh

Abstract Background Ghana did not meet the Millennium Development Goal 4 of reducing child mortality by two-thirds and may not meet SDG (2030). There is a need to direct scarce resources to mitigate the impact of the most important risk factors influencing high neonatal deaths. This study applied both spatial and non-spatial regression models to explore the differential impact of environmental, maternal, and child associated risk factors on neonatal deaths in Ghana. Methods The study relied on data from the Ghana Demographic and Health Surveys (GDHS) and the Ghana Maternal Health Survey (GMHS) conducted between 1998 and 2017 among 49,908 women of reproductive age and 31,367 children under five (GDHS-1998 = 3298, GDHS-2003 = 3844, GDHS-2008 = 2992, GDHS-2014 = 5884, GMHS-2017 = 15,349). Spatial Autoregressive Models that account for spatial autocorrelation in the data at the cluster-level and non-spatial statistical models with appropriate sampling weight adjustment were used to study factors associated with neonatal deaths, and a p-value less than 0.05 was considered statistically significant. Results Population density, multiple births, smaller household sizes, high parity, and low birth weight significantly increased the risk of neonatal deaths over the years. Among mothers who had multiple births, the risk of having neonatal deaths was approximately four times as high as the risk of neonatal deaths among mothers who had only single birth [aRR = 3.42, 95% CI: 1.63–7.17, p < 0.05]. Neonates who were perceived by their mothers to be small were at a higher risk of neonatal death compared to very large neonates [aRR = 2.08, 95% CI: 1.19–3.63, p < 0.05]. A unit increase in the number of children born to a woman of reproductive age was associated with a 49% increased risk in neonatal deaths [aRR = 1.49, 95% CI: 1.30–1.69, p < 0.05]. Conclusion Neonatal mortality in Ghana remains relatively high, and the factors that predisposed children to neonatal death were birth size that were perceived to be small, low birth weight, higher parity, and multiple births. Improving pregnant women’s nutritional patterns and providing special support to women who have multiple deliveries will reduce neonatal mortality in Ghana.


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