Body mass index in pediatric kidney transplant selection criteria.

BACKGROUND: Obesity is associated with increased complications, rejection, and graft loss after kidney transplantation in adult and pediatric recipients. Elevated body mass index (BMI) is a common contraindication to transplant at adult kidney transplant programs; however, there is no data on such limitations for pediatric patients. METHODS: Between October and December 2022, we conducted a survey of Pediatric Nephrology Research Consortium centers assessing the use of BMI in pediatric kidney transplant evaluation. Centers reporting utilization of BMI cutoffs were invited to submit patient-level data on children declined for active transplant listing due to BMI. RESULTS: Thirty-nine centers responded to the survey (42% response rate); 51% include BMI in their written listing criteria, with a median BMI "cutoff" of 39 kg/m2 (range 30-50 kg/m2). Between January 1, 2016, and December 31, 2021, 30 children at 15 transplant centers were declined for listing status due to BMI. Patient-level data was provided for 19 children (63%) who were denied active listing status; median BMI was 42 kg/m2 (range 35.8-49.4 kg/m2) and 84% were on dialysis. One year after evaluation, seven patients (37%) had proceeded to active wait list status. Eight (42%) remained in inactive status and four (21%) were unlisted; ten of these 12 patients (83%) were on dialysis. CONCLUSIONS: The use of BMI in pediatric kidney transplant evaluation and listing varies among centers, but BMI limits access to transplant for some children. More information is needed on the outcomes of obese pediatric kidney candidates who are and are not transplanted, to guide development of national and international consensus.

A potential role for insulin treatment during pregnancy in reducing postpartum psychological distress in maternal obesity: an administrative population health study.

BACKGROUND: Studies have found an association between obesity and an increased risk for peripartum depression, which has also been linked to decreased placental lactogen levels. In addition, women with obesity treated for gestational diabetes with insulin were found to have increased levels of placental lactogen. Treatment options exist for perinatal and postpartum depression however they pose a risk to the developing offspring. Thus, prevention as well as markers for early identification of peripartum depression are needed. Therefore, our study objective is to identify the association between insulin treatment in pregnancy and the risk of postpartum psychological distress (abbreviated here as PPD) among cohorts of women with and without obesity. METHODS: Administrative health data (2002/03-2018/19) were used to identify a cohort of women (age 15+ years) who gave birth (N = 250,746) and had no pre-existing mood/anxiety disorders or diabetes (N = 222,863 excluded). Women were then divided into two groups: lean (N = 17,975) and with obesity (N = 9908), which was identified by a recorded maternal weight of > 38 to < 65.6 kg and ≥ 85 to < 186 kg (respectively). The risk of PPD within one year after delivery with and without insulin treatment was assessed by Poisson regression analysis. Models were adjusted for maternal age group (at pregnancy start date) and area-level income (at delivery). RESULTS: The unadjusted risk of PPD was higher in the obesity group (8.56%; 95% CI 8.00-9.15) than in the lean group (6.93%; 95% CI 6.56-7.33). When no insulin treatment was given during pregnancy, mothers with obesity had a significantly higher risk of PPD than the lean group (aRR 1.27; 95% CI 1.17-1.39; p < 0.0001). However, when women with obesity and insulin treatment were compared to the lean group with no insulin treatment, no significant difference in the risk of PPD was observed between the groups (aRR 1.30; 95% CI 0.83-2.02; p = 0.248). CONCLUSION: This is the first study to demonstrate a positive association between insulin treatment in pregnancy among women with obesity and reduced PPD rates, suggesting insulin as a possible preventative measure. However, the biological mechanism behind the observed positive effect of insulin on PPD rates remains to be investigated.

Obesity and regulation of human placental lactogen production in pregnancy.

The four genes coding for placental members of the human (h) growth hormone (GH) family include two that code independently for placental lactogen (PL), also known as chorionic somatomammotrophin hormone, one that codes for placental growth hormone (PGH) and a pseudogene for which RNA but no protein product is reported. These genes are expressed preferentially in the villus syncytiotrophoblast of the placenta in pregnancy. In higher primates, the placental members, including hPL and PGH, are the result of multiple duplication events of the GH gene. This contrasts with rodents and ruminants, where PLs result from duplication of the prolactin (PRL) gene. Thus, unlike their mouse counterparts, the hPL and PGH hormones bind both lactogenic and somatogenic receptors with varying affinity. Roles influenced by nutrient availability in both metabolic control in pregnancy and maternal behaviour are supported. However, the effect maternal obesity has on the activation of placental members of the hGH gene family, particularly the expression and function of those genes, is poorly understood. Evidence from partially humanised hGH/PL transgenic mice indicates that both the remote upstream hPL locus control region (LCR) and more gene-related regulatory regions are required for placental expression in vivo. Furthermore, a specific pattern of interactions between the LCR and hPL gene promoter regions is detected in term placenta chromatin from women with a normal body mass index (BMI) in the range 18.5-25 kg m-2 by chromosome conformation capture assay. This pattern is disrupted with maternal obesity (class II BMI > 35 kg m-2 ) and associated with a > 40% decrease in term hPL RNA levels, as well as serum hPL but not PRL levels, during pregnancy. The relative importance of the chromosomal architecture and predicted properties for transcription factor participation in terms of hPL production and response to obesity are considered, based on comparison with components required for efficient human pituitary GH gene expression.

A useful model to compare human and mouse growth hormone gene chromosomal structure, expression and regulation, and immune tolerance of human growth hormone analogues.

Human (h) pituitary growth hormone (GH) is both physiologically and clinically important. GH reaches its highest circulatory levels in puberty, where it contributes to energy homeostasis and somatogenic growth. GH also helps to maintain tissues and organs and, thus, health and homeostasis. A reduction in the rate of hGH production begins in middle age but if GH insufficiency occurs this may result in tissue degenerative and metabolic diseases. As a consequence, hGH is prescribed under conditions of GH deficiency and, because of its lipolytic activity, stimulation of hGH release has also been used to treat obesity. However, studies of normal GH production and particularly synthesis versus secretion are not feasible in humans as they require sampling normal pituitaries from living subjects. Furthermore, human (or primate) GH structure and, as such, regulation and potential function, is distinct from non-primate rodent GH. As a result, most information about hGH regulation comes from measurements of secreted levels of GH in humans. Thus, partially humanized hGH transgenic mice, generated containing fragments of human chromosome 17 that include the intact hGH gene locus and many thousands of flanking base pairs as well as the endogenous mouse (m) GH gene provide a potentially useful model. Here we review this mouse model in terms of its ability to allow comparison of hGH versus mGH gene expression, and specifically: (i) GH locus structure as well as regulated and rhythmic expression; (ii) their ability to model a clinical assessment of hGH production in response to overeating and hyperinsulinemia as well as a possible effect of exercise, and (iii) their hGH-related immune tolerance and thus potential for testing hGH-related analogue immunogenicity.

Chromosomal architecture and placental expression of the human growth hormone gene family are targeted by pre-pregnancy maternal obesity.

The human (h) placental lactogenic hormone chorionic somatomammotropin (CS) is highly produced during pregnancy and acts as a metabolic adaptor in response to maternal insulin resistance. Maternal obesity can exacerbate this "resistance", and a >75% decrease in CS RNA levels was observed in term placentas from obese vs. lean women. The genes coding for hCS ( hCS-A and hCS-B) and placental growth hormone ( hGH-V) as well as the hCS-L pseudogene and pituitary growth hormone (GH) gene ( hGH-N) are located at a single locus on chromosome 17. Three remote hypersensitive sites (HS III-V) located >28 kb upstream of hGH-N as well as local hCS gene promoter and enhancer regions are implicated in hCS gene expression. A placenta-specific chromosomal architecture, including interaction between HS III-V and hCS but not hGH gene promoters, was detected in placentas from lean women (BMI <25 kg/m2) by using the chromosome conformation capture assay. This architecture was disrupted by pre-pregnancy maternal obesity (BMI >35 kg/m2), resulting in a predominant interaction between HS III and the hGH-N promoter, which was also observed in nonplacental tissues. This was accompanied by a decrease in hCS levels, which was consistent with reduced RNA polymerase II and CCAAT/enhancer-binding protein-ß association with individual hCS promoter and enhancer sequences, respectively. Thus, pre-pregnancy maternal obesity disrupts the placental hGH/CS gene locus chromosomal architecture. However, based on data from obese women who develop GDM, insulin treatment partially recapitulates the chromosomal architecture seen in lean women and positively affects hCS production, presumably facilitating prolactin receptor-related signaling by hCS.

Expression of Placental Members of the Human Growth Hormone Gene Family Is Increased in Response to Sequential Inhibition of DNA Methylation and Histone Deacetylation.

The genes coding for human (h) chorionic somatomammotropin (CS), hCS-A and hCS-B, and placental growth hormone (GH-V), hGH-V, are located at a single locus on chromosome 17. Efficient expression of these placental genes has been linked to local regulatory (5' P and 3' enhancer) sequences and a remote locus control region (LCR), in part, through gene transfer in placental and nonplacental tumor cells. However, low levels of endogenous hCS/GH-V transcripts are reported in the same cells compared with term placenta, suggesting that chromatin structure, or regulatory region accessibility, versus transcription factor availability contributes to the relatively low levels. To assess individual hCS-A, CS-B, and GH-V gene expression in placental and nonplacental tumor cells and the effect of increasing chromatin accessibility by inhibiting DNA methylation and histone deacetylation using 5-aza-2'-deoxycytidine (azadC) and trichostatin A (TSA). Low levels of hCS-A, CS-B, and GH-V were detected in placental and nonplacental tumor cells compared with term placenta. A significant >5-fold increase in activity was seen in placental, but not nonplacental, cells transfected with hybrid hCS promoter luciferase genes containing 3' enhancer sequences. Pretreatment of placental JEG-3 cells with azadC resulted in a >10-fold increase in hCS-A, CS-B, and GH-V RNA levels with TSA treatment compared with TSA treatment alone. This effect was specific as reversing the treatment regimen did not have the same effect. An assessment of hyperacetylated H3/H4 in JEG-3 cells treated with azadC and TSA versus TSA alone revealed significant increases consistent with a more open chromatin structure, including the hCS 3' enhancer sequences and LCR. These observations suggest that accessibility of remote and local regulatory regions required for efficient placental hGH/CS expression can be restricted by DNA methylation and histone acetylation status. This includes restricting access of the hCS 3' enhancer sequences to available placental enhancer transcription factors.

Cooking schools improve nutrient intake patterns of people with type 2 diabetes.

OBJECTIVE: To determine whether cooking classes offered by the Cooperative Extension Service improved nutrient intake patterns in people with type 2 diabetes. DESIGN: Quasi-experimental using pretest, posttest comparisons. SETTING: Community locations including schools, churches, and senior centers. PARTICIPANTS: One hundred seventeen people with type 2 diabetes, from diverse ethnic and socioeconomic backgrounds. INTERVENTION: Series of classes for people with type 2 diabetes and their family members that incorporated Social Cognitive Theory tenets. The classes featured current nutrition recommendations for people with type 2 diabetes and hands-on cooking, where participants prepared and ate a meal together. MAIN OUTCOME MEASURES: Three-day food records, completed prior to attending cooking schools and 1 month after, were used to measure changes in energy intake and selected nutrients. ANALYSIS: Program efficacy was assessed using the Wilcoxon signed-rank test to compare differences between pre-training and post-training variables. ANCOVA was used to determine whether program efficacy was affected by sociodemographics. RESULTS: Participants decreased (P < .05) intakes of energy, fat grams, percentage of calories from fat, saturated fat grams, cholesterol (mg), sodium (mg), and carbohydrate grams. CONCLUSIONS AND IMPLICATIONS: Nutrition education incorporating hands-on cooking can improve nutrient intake in people with type 2 diabetes from diverse ethnic and socioeconomic backgrounds.

Embryonic survival and severity of cardiac and craniofacial defects are affected by genetic background in fibroblast growth factor-16 null mice.

Disruption of the X-chromosome fibroblast growth factor 16 (Fgf-16) gene, a member of the FGF-9 subfamily with FGF-20, was linked with an effect on cardiac development in two independent studies. However, poor trabeculation with lethality by embryonic day (E) 11.5 was associated with only one, involving maintenance in Black Swiss (Bsw) versus C57BL/6 mice. The aim of this study was to examine the potential influence of genetic background through breeding the null mutation onto an alternate (C57BL/6) background. After three generations, 25% of Fgf-16(-/Y) mice survived to adulthood, which could be reversed by reducing the contribution of the C57BL/6 genetic background by back crossing to another strain. There was no significant difference between FGF-9 and FGF-20 RNA levels in Fgf-16 null versus wild-type mice regardless of strain. However, FGF-8 RNA levels were reduced significantly in Bsw but not C57BL/6 mice. FGF-8 is linked to anterior heart development and like the FGF-9 subfamily is reportedly expressed at E10.5. Like FGF-16, neuregulin as well as signaling via ErbB2 and ErbB4 receptors have been linked to trabeculae formation and cardiac development around E10.5. Basal neuregulin, ErbB2, and ErbB4 as well as FGF-8, FGF-9, and FGF-16 RNA levels varied in Bsw versus C57BL/6 mice. These data are consistent with the ability of genetic background to modify the phenotype and affect embryonic survival in Fgf-16 null mice.

Strategies of Asian, Hispanic, and non-Hispanic white parents to influence young adolescents' intake of calcium-rich foods, 2004 and 2005.

INTRODUCTION: Optimal intake of dietary calcium is critical to prevent osteoporosis later in life, yet most young adolescents do not consume the recommended amount. We describe parental strategies that can influence young adolescents' calcium intake in Asian, Hispanic, and non-Hispanic white households METHODS: A qualitative research design employed semistructured individual interviews with a convenience sample of mostly female parents self-reported as Asian (n = 48), Hispanic (n = 44), or non-Hispanic white (n = 76) having a child aged 10 to 13 years at home. Interviews were conducted in homes or community centers in 12 states. Interview data were analyzed by using qualitative data analysis software and thematic content analysis procedures. RESULTS: Parents monitored calcium intake by making calcium-rich foods available, preparing calcium-rich foods, and setting expectations that children would consume calcium-rich foods. As mentors, parents encouraged intake of calcium-rich foods and advised children to moderate or increase intake of specific foods. Although parents perceived modeling of calcium intake as important, some were ambivalent about its effects. We noted minimal differences by racial/ethnic groups and sex of children in reported availability of selected calcium-rich foods at home, parental modeling of intake, and mentoring behaviors. CONCLUSION: Our findings suggest that interventions to help parents increase children's intake of calcium should focus on types of foods made available, giving age-appropriate encouragement and advice, and modeling proper intake.

At-home and away-from-home eating patterns influencing preadolescents' intake of calcium-rich food as perceived by Asian, Hispanic and Non-Hispanic white parents.

OBJECTIVE: To explore at-home and away-from-home eating patterns influencing Asian, Hispanic, and non-Hispanic white preadolescents' intake of calcium-rich food from a parental perspective. DESIGN: Individual semistructured interviews. SETTING: Home or community site. PARTICIPANTS: Convenience sample (n = 201) of self-reported Asian (n = 54), Hispanic (n=57), and non-Hispanic white (n = 90) parents of 10- to 13-year-old children recruited from community youth programs. PHENOMENON OF INTEREST: Description of at-home and away-from-home family eating patterns. ANALYSIS: NVivo software to code and sort transcript segments, qualitative data analysis procedures. RESULTS: Participants from all groups shared common at-home and away-from-home meal patterns. A lack of time often resulted in negative factors that impacted intake of calcium-rich food and beverages including breakfast on the run, fewer home-prepared or shared family meals, and more frequent meals eaten away from home. Asian and Hispanic parents indicated eating out less frequently than non-Hispanic white parents. Parents from all groups lacked expectations for their child to drink calcium-rich beverages with meals. CONCLUSIONS AND IMPLICATIONS: Practical strategies are needed to facilitate intake of calcium-rich food and beverages through more frequent family meals at home and parental expectations for children's intake of calcium-rich beverages with meals.

Inhibition of TGFbeta signaling potentiates the FGF-2-induced stimulation of cardiomyocyte DNA synthesis.

OBJECTIVE: Added transforming growth factor beta (TGFbeta) inhibits the proliferation of immature cardiomyocytes. We have now examined the hypothesis that suppression of endogenous TGFbeta signaling will boost the proliferative response (DNA synthesis) of cardiac myocytes to serum and/or to the mitogenic factor fibroblast growth factor-2 (FGF-2). METHODS AND RESULTS: Overexpression of a kinase-deficient TGFbeta type II receptor (TGFbetaRIIDeltaKD) resulted in a 2.8-fold increase in cardiomyocyte DNA synthesis in serum-rich cultures, an effect requiring active FGFR-1 since it was not observed in the presence of excess kinase-deficient FGFR-1. This finding suggested that endogenous TGFbeta-TGFbetaRII suppressed endogenous FGFR-1-mediated signals that stimulate or are permissive for DNA synthesis. TGFbeta had no effect, however, on the FGF-2-induced acute stimulation of extracellular signal regulated kinase1/2. FGF-2, added in the absence or presence of TGFbeta inhibition, elicited a 3- or a 13-fold stimulation of DNA synthesis, respectively, pointing to a synergistic effect. CONCLUSION: Inhibition of TGFbetaRII-transduced signaling upregulates the proliferative response of cardiomyocytes to serum, and greatly potentiates the stimulatory effect of FGF-2. A combinatorial strategy including activation of FGF-2 and inhibition of TGFbeta-triggered signal transduction may be required for maximal stimulation of immature cardiomyocyte DNA synthesis.

Development of a food frequency questionnaire to estimate calcium intake of Asian, Hispanic, and white youth.

OBJECTIVE: To develop a food frequency questionnaire (FFQ) that estimates calcium intake of Asian, Hispanic, and white youth living in the western United States. DESIGN: A list of 80 foods was assembled to create an FFQ to measure calcium intake. Evaluation of the FFQ spanned four consecutive weeks. An FFQ was completed during Week 1 and Week 4, and a 24-hour dietary recall was completed during Week 2 and Week 3.Subjects/setting A convenience sample of 162 Asian, Hispanic, and white youth ages 10 to 18 years was selected. Statistical analyses performed Percent agreement, paired t tests, Pearson correlation coefficients of cube-root transformed values, and deattenuated Pearson correlation coefficients of cube-root transformed values were used to evaluate the FFQ. RESULTS: The correlation between calcium intake estimates, when measured by first and second administrations of the FFQ, was 0.68 (Pearson's r) for the total sample. Correlations differed by age, sex, and ethnic subgroups as follows: 10 to 13 years (r=0.62), 14 to 18 years (r=0.73), male (r=0.73), female (r=0.64), Asian (r=0.77), Hispanic (r=0.72), and white (r=0.48). The correlation between calcium intakes as estimated by the second FFQ vs the average of the two 24-hour dietary recalls was 0.54 (deattenuated Pearson's r) for the total sample. This correlation differed by age, sex, and ethnic subgroups as follows: 10 to 13 years (r=0.46), 14 to 18 years (r=0.59), male (r=0.65), female (r=0.45), Asian (r=0.64), Hispanic (r=0.18), and white (r=0.57). CONCLUSIONS: A unique dietary survey has been developed to estimate calcium intake among Asian, Hispanic, and white youth in the United States.

Calcium intake of Asian, Hispanic and white youth.

OBJECTIVE: To examine calcium intake and food sources among Asian, white and Hispanic youth, in order to develop and target interventions to improve calcium intake. METHODS: Cross-sectional survey with two 24-hour dietary recalls one week apart. Calcium intake was evaluated in 167 male and female adolescents of Asian, Hispanic and white ethnicity, ages 10-18 years, from six states. Main outcome measures were mean daily calcium intake (mg/day). STATISTICAL ANALYSES PERFORMED: t tests, Chi-square and analysis of variance for differences by age, ethnicity and gender, multiple regression of factors influencing calcium intake. RESULTS: Overall median calcium intake was 938 mg/day with 868 mg/day for Asians, 1180 mg/day for whites and 896 mg/day for Hispanics. Daily milk intake was the primary predictor of calcium intake with Asian ethnicity and female gender each showing a negative association to calcium intake in multiple regression models. CONCLUSIONS: Milk intake was the primary factor positively influencing calcium intake, while Asian ethnicity and female gender negatively influenced calcium intake. Thus, interventions to improve calcium intake should focus on improving milk intake of Asians and females.

Perspectives on intake of calcium-rich foods among Asian, Hispanic, and white preadolescent and adolescent females.

OBJECTIVE: Declining calcium intake among adolescents warrants attention. Our objective was to identify influences on adolescents' consumption of calcium-rich foods. DESIGN: Focus groups were conducted with girls representing 2 age groups (11 to 12 or 16 to 17 years) and 3 macroethnic groups (Asian, Hispanic, or white). SETTING: Public schools in 10 states. PARTICIPANTS: A convenience sample (n = 200) was recruited through schools. VARIABLES MEASURED: Focus groups (n = 35) were audiotaped and transcribed. Influences relative to consumption of milk or other calcium-rich foods were identified. ANALYSIS: Comments were coded as motivators or barriers within each focus group. Content analysis procedures were used to compare ethnic and age groups. RESULTS: A barrier to milk consumption that was more common among older girls and Asian groups was the limited expectation within families for drinking milk. Many controlled their own beverage choices, and milk, even if liked, was only one option. Milk was positively associated with strength and bone health, but these attributes were viewed as being more important for boys than girls. Milk was associated with breakfast, school lunches, cereal, and desserts. White girls had the most positive reactions to milk and Hispanic girls the most negative. All groups were positive toward pizza, ice cream, and cheese. CONCLUSIONS AND IMPLICATIONS: To improve calcium intake among teens, interventions should include a family component, stress the benefits of milk for girls, and focus on breakfast.