Relation between obesity-related comorbidities and kidney function estimation in children.

BACKGROUND: The current childhood obesity pandemic is likely to result in an increased risk of chronic kidney disease (CKD) later in life. Correlations between obesity-related comorbidities and kidney function can be found, but it is unclear to what extent this is caused by bias due to different mathematical forms of the estimated glomerular filtration rate (eGFR) equations. The present study aimed to analyze correlations between obesity-related comorbidities and different eGFR equations and to investigate whether rescaled serum creatinine (SCr/Q) for sex and age or height might be an alternative biomarker for kidney function estimation. METHODS: This cross-sectional cohort study included 600 children with overweight and obesity. Mean age was 12.20 ± 3.28 years, 53.5% were female, and mean BMI z-score was 3.31 ± 0.75. All children underwent a comprehensive assessment that included anthropometrical and blood pressure measurements, laboratory examination, air displacement plethysmography, and polysomnography. Qage and Qheight polynomials were used to rescale SCr and multiple creatinine-based eGFR equations were compared. RESULTS: SCr/Q and almost all GFR estimations significantly correlated with a waist-to-hip ratio, fat mass, homeostasis model assessment for insulin resistance, and triacylglyceride, HDL cholesterol, alanine transaminase, and serum uric acid concentrations. Multiple correlations, however, were not confirmed by all equations, which suggests dependency on the mathematical form of the different eGFR equations. CONCLUSIONS: Correlations between obesity-related comorbidities and creatinine-based eGFR are present in children with overweight and obesity, but depend to a large extent on the eGFR equation of choice. SCr/Q might be an alternative biomarker for assessing correlations between obesity-related comorbidities and kidney function in children with overweight and obesity. A higher resolution version of the Graphical abstract is available as Supplementary information.

Serum CathepsinD in pregnancy: Relation with metabolic and inflammatory markers and effects of fish oils and probiotics.

BACKGROUND AND AIMS: Elevated circulating levels of CathepsinD (CatD) have been linked to metabolic deviations including liver inflammation. We investigated 1) whether supplementation with probiotics and/or fish oil affects CatD and 2) whether the CatD concentration would associate with gestational diabetes (GDM), low-grade inflammation, lipid metabolism, body fat % and dietary composition. METHODS AND RESULTS: Overweight/obese pregnant women (n = 438) were randomized into fish oil + placebo, probiotics + placebo, fish oil + probiotics or placebo + placebo groups. Fish oil contained 1.9 g docosahexaenoic acid and 0.22 g eicosapentaenoic acid and probiotics were Lacticaseibacillusrhamnosus HN001 (formerly Lactobacillusrhamnosus HN001) and Bifidobacteriumanimalis ssp. lactis 420, 1010 colony-forming units each). Serum CatD levels were analysed by ELISA, GlycA and lipid metabolites by NMR, high sensitive C-reactive protein (hsCRP) by immunoassay, and intakes of energy yielding nutrients and n-3 and n-6 fatty acids from food diaries at both early and late pregnancy. GDM was diagnosed by OGTT. CatD concentrations did not differ between the intervention groups or by GDM status. Multivariable linear models revealed that body fat % and GlycA affected CatD differently in healthy women and those with GDM. CONCLUSION: The serum CatD concentration of pregnant women was not modified by this dietary intervention. Serum CatD was influenced by two parameters, body fat and low grade inflammation, which were dependent on the woman's GDM status. CLINICAL TRIAL REG. NO: NCT01922791, clinicaltrials.gov (secondary analysis).

Narrative Review: Nutrient Deficiencies in Adults and Children with Treated and Untreated Celiac Disease.

Nutrient deficiencies are well recognized as secondary consequences of celiac disease (CD) and closely related to the clinical presentation of affected patients. Despite their clinical significance, consensus is lacking on the pattern and frequency of nutrient deficiencies in CD, the usefulness of their assessment at the time of diagnosis and during follow-up. This review aims to provide an overview of nutrient deficiencies among pediatric and adult CD patients at diagnosis and on a gluten-free diet (GFD), and their potential causes in CD. Secondly, we review their impact on CD management strategies including the potential of nutrient supplementation. A search of Medline, Pubmed and Embase until January 2019 was performed. Despite a high variability between the reported deficiencies, we noted that nutrient deficiencies occur frequently in children and adults with CD at diagnosis and during treatment with a GFD. Both inadequate dietary intake and/or diminished uptake due to intestinal dysfunction contribute to nutrient deficiencies. Most deficiencies can be restored with (long-term) treatment with a GFD and/or supplementation. However, some of them persist while others may become even more prominent during GFD. Our results indicate a lack of comprehensive evidence on the clinical efficacy of nutrient supplementation in CD management highlighting the need for further studies.

Modifying Serum Plant Sterol Concentrations: Effects on Markers for Whole Body Cholesterol Metabolism in Children Receiving Parenteral Nutrition and Intravenous Lipids.

BACKGROUND: Non-cholesterol sterols are validated markers for fractional intestinal cholesterol absorption (cholestanol) and endogenous cholesterol synthesis (lathosterol). This study's objective was to evaluate markers for cholesterol synthesis and absorption in children exposed to two different intravenous lipid emulsions that rapidly change serum plant sterol concentrations as part of their parenteral nutrition (PN). METHODS: Serum samples from two different studies were used: (1) nine PN-dependent children with intestinal failure associated liver disease (IFALD) whose soy-based, plant sterol-rich lipid (SO) was replaced with a fish-based, plant sterol-poor (FO) lipid; and (2) five neonates prescribed SO after birth. In the first study, samples were collected at baseline (prior to FO initiation) and after 3 and 6 months of FO. In study 2, samples were collected at 1 and 3 weeks of age. RESULTS: In study 1, a 7-fold reduction in campesterol, a 12-fold reduction in sitosterol, and a 15-fold reduction in stigmasterol was observed 6 months after switching to FO. Serum cholesterol concentrations did not change, but cholesterol-standardized lathosterol increased (3-fold) and cholesterol-standardized cholestanol decreased (2-fold). In study 2, after 3 weeks of SO, sitosterol and campesterol concentrations increased 4-5 fold. At the same time, cholesterol-standardized lathosterol increased 69% and cholesterol-standardized cholestanol decreased by 29%. CONCLUSION: Based on these finding we conclude that changes in serum plant sterol concentrations might have direct effects on endogenous cholesterol synthesis, although this needs to be confirmed in future studies. Moreover, we speculate that this changed synthesis subsequently affects intestinal cholesterol absorption.

Consumption of gluten with gluten-degrading enzyme by celiac patients: a pilot-study.

AIM: To assesses the safety and efficacy of Aspergillus niger prolyl endoprotease (AN-PEP) to mitigate the immunogenic effects of gluten in celiac patients. METHODS: Patients with initial diagnosis of celiac disease as confirmed by positive serology with subtotal or total villous atrophy on duodenal biopsies who adhere to a strict gluten-free diet (GFD) resulting in normalised antibodies and mucosal healing classified as Marsh 0 or I were included. In a randomised double-blind placebo-controlled pilot study, patients consumed toast (approximately 7 g/d gluten) with AN-PEP for 2 wk (safety phase). After a 2-wk washout period with adherence of the usual GFD, 14 patients were randomised to gluten intake with either AN-PEP or placebo for 2 wk (efficacy phase). Measurements at baseline included complaints, quality-of-life, serum antibodies, immunophenotyping of T-cells and duodenal mucosa immunohistology. Furthermore, serum and quality of life questionnaires were collected during and after the safety, washout and efficacy phase. Duodenal biopsies were collected after the safety phase and after the efficacy phase. A change in histological evaluation according to the modified Marsh classification was the primary endpoint. RESULTS: In total, 16 adults were enrolled in the study. No serious adverse events occurred during the trial and no patients withdrew during the trial. The mean score for the gastrointestinal subcategory of the celiac disease quality (CDQ) was relatively high throughout the study, indicating that AN-PEP was well tolerated. In the efficacy phase, the CDQ scores of patients consuming gluten with placebo or gluten with AN-PEP did not significantly deteriorate and moreover no differences between the groups were observed. During the efficacy phase, neither the placebo nor the AN-PEP group developed significant antibody titers. The IgA-EM concentrations remained negative in both groups. Two patients were excluded from entering the efficacy phase as their mucosa showed an increase of two Marsh steps after the safety phase, yet with undetectable serum antibodies, while 14 patients were considered histologically stable on gluten with AN-PEP. Also after the efficacy phase, no significant deterioration was observed regarding immunohistological and flow cytometric evaluation in the group consuming placebo compared to the group receiving AN-PEP. Furthermore, IgA-tTG deposit staining increased after 2 wk of gluten compared to baseline in four out of seven patients on placebo. In the seven patients receiving AN-PEP, one patient showed increased and one showed decreased IgA-tTG deposits. CONCLUSION: AN-PEP appears to be well tolerated. However, the primary endpoint was not met due to lack of clinical deterioration upon placebo, impeding an effect of AN-PEP.

Arginine appearance and nitric oxide synthesis in critically ill infants can be increased with a protein-energy-enriched enteral formula.

BACKGROUND: Arginine is considered an essential amino acid during critical illness in children, and supplementation of arginine has been proposed to improve arginine availability to facilitate nitric oxide (NO) synthesis. Protein-energy-enriched enteral formulas (PE-formulas) can improve nutrient intake and promote anabolism in critically ill infants. However, the effect of increased protein and energy intake on arginine metabolism is not known. OBJECTIVE: We investigated the effect of a PE-formula compared with that of a standard infant formula (S-formula) on arginine kinetics in critically ill infants. DESIGN: A 2-h stable-isotope tracer protocol was conducted in 2 groups of critically ill infants with respiratory failure because of viral bronchiolitis, who received either a PE-formula (n = 8) or S-formula (n = 10) in a randomized, blinded, controlled setting. Data were reported as means ± SDs. RESULTS: The intake of a PE-formula in critically ill infants (aged 0.23 ± 0.14 y) resulted in an increased arginine appearance (PE-formula: 248 ± 114 µmol · kg(-1) · h(-1); S-formula: 130 ± 53 µmol · kg(-1) · h(-1); P = 0.012) and NO synthesis (PE-formula: 1.92 ± 0.99 µmol · kg(-1) · h(-1); S-formula: 0.84 ± 0.36 µmol · kg(-1) · h(-1); P = 0.003), whereas citrulline production and plasma arginine concentrations were unaffected. CONCLUSION: In critically ill infants with respiratory failure because of viral bronchiolitis, the intake of a PE-formula increases arginine availability by increasing arginine appearance, which leads to increased NO synthesis, independent of plasma arginine concentrations. This trial was registered at www.trialregister.nl as NTR515.