Heather E. Price

25-Hydroxyvitamin D and Cardiovascular Risk Factors in Women with Systemic Lupus Erythematosus

OBJECTIVE Low serum levels of 25-hydroxyvitamin D (25[OH]D; vitamin D) are associated with a higher frequency of cardiovascular disease and risk factors in the general population. Vitamin D deficiency has also been noted in systemic lupus erythematosus (SLE). The objective of this study was to evaluate the associations of serum 25(OH)D levels with cardiovascular risk factors in women with SLE. METHODS Data collected in 181 women with SLE included demographics, SLE activity and damage assessments, cardiovascular risk factors, medications, and laboratory assessments of inflammatory markers and 25(OH)D levels. Multiple linear and logistic regressions were used to estimate the association of 25(OH)D levels with cardiovascular risk factors. RESULTS The mean age and disease duration were 43.2 and 11.9 years, respectively. The mean 25(OH)D level was 27.1 ng/ml and 62.2% had 25(OH)D levels <30 ng/ml. In unadjusted analyses, lower 25(OH)D levels were significantly associated with higher diastolic blood pressure, low-density lipoprotein cholesterol, lipoprotein(a), body mass index (BMI), and fibrinogen levels, as well as self-reported hypertension and diabetes mellitus. Lower 25(OH)D levels were also significantly associated with higher SLE disease activity and damage scores. After adjustment for age, seasonal variation, and race/ethnicity, lower 25(OH)D levels were also significantly related to higher fasting serum glucose. With further adjustment for BMI, associations between 25(OH)D and cardiovascular risk factors were no longer significant. CONCLUSION This study demonstrates that vitamin D levels are low in women with SLE and significant associations exist with selected cardiovascular risk factors, although most of these associations can be explained by BMI.

Hypophosphatemia with Elevations in Serum Fibroblast Growth Factor 23 in a Child with Jansen’s Metaphyseal Chondrodysplasia

CONTEXT Previous studies have suggested a regulatory relationship between serum phosphorus, vitamin D, and fibroblast growth factor 23 (FGF23), a hormone that promotes renal excretion of phosphate. Despite these associations, the identity of the primary regulator of serum FGF23 is unresolved. Jansens metaphyseal chondrodysplasia is a rare autosomal dominant disorder associated with short-limbed dwarfism and other characteristic skeletal abnormalities. This condition is caused by mutations in the PTH/PTHrP receptor that result in ligand-independent cAMP accumulation, thus rendering the receptor constitutively active. These patients typically exhibit asymptomatic hypercalcemia and hypophosphatemia despite low or undetectable serum levels of PTH and PTHrP. EVIDENCE ACQUISITION A literature search revealed that serum FGF23 levels had not been studied in patients with Jansens syndrome, a disorder in which the biochemical features present a unique opportunity to study the possible relationship between FGF23 and calcium-phosphorus-vitamin D metabolism. A case of Jansens syndrome is presented in which serum FGF23 concentrations, along with serum phosphorus and 1,25(OH)(2) vitamin D levels, were measured and compared with those of age-matched controls. EVIDENCE SYNTHESIS Serum FGF23 concentrations in the patient with Jansens syndrome were found to be markedly and persistently elevated, compared with values in healthy, age-matched controls, despite hypophosphatemia and normal 1,25(OH)(2) vitamin D levels. CONCLUSION Together, our findings indicate that serum FGF23 could be governed by factor(s) other than serum phosphorus, potentially by activation of the PTH/PTHrP receptor in bone.

Synthesis of vitamin D in skin after burns

Severe burn injury is associated with vitamin D deficiency, low bone turnover, and abnormalities in calcium homoeostasis. Patients do not routinely receive vitamin D supplementation and sun exposure is currently not controlled. By analysis of skin biopsy samples for vitamin D3 precursors after exposure to ultraviolet B light we found that the conversion of 7-dehydrocholesterol to previtamin D3 was reduced in children a mean of 14 months after the burn. Low serum 25-hydroxyvitamin D concentrations were also found. We conclude that vitamin D supplementation is necessary after burn injury.

Gene-vitamin D interactions on food sensitization: a prospective birth cohort study

To cite this article: Liu X, Wang G, Hong X, Wang D, Tsai H‐J, Zhang S, Arguelles L, Kumar R, Wang H, Liu R, Zhou Y, Pearson C, Ortiz K, Schleimer R, Holt P, Pongracic J, Price HE, Langman C, Wang X. Gene–vitamin D interactions on food sensitization: a prospective birth cohort study. Allergy 2011; 66: 1442–1448.

Serum Soluble Urokinase-Type Plasminogen Activator Receptor Levels and Idiopathic FSGS in Children: A Single-Center Report

BACKGROUND AND OBJECTIVES FSGS is the primary cause of childhood nephrotic syndrome leading to ESRD. Permeability factors, including circulating serum soluble urokinase-type plasminogen activator receptor (suPAR), have been postulated as putative causes in adults with primary FSGS. Similar results have yet to be proven in children. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This cross-sectional single-center study assessed the association of serum suPAR in children with FSGS or other glomerular and nonglomerular kidney diseases. RESULTS This study examined 110 samples retrieved from 99 individuals (between January 2011 and April 2012), aged 1-21 years; of these individuals, 20 had primary FSGS, 24 had non-FSGS glomerular disease, 26 had nonglomerular kidney disease, and 29 were healthy controls. suPAR levels were not significantly different in children with FSGS, non-FSGS glomerular disease, and healthy controls (P>0.05). However, suPAR levels (median [25%-75%]) were higher in children with nonglomerular kidney disease (3385 pg/ml [2695-4392]) versus FSGS (2487 pg/ml [2191-3351]; P<0.05). Female patients with nephrotic-range proteinuria (U-Pr/Cr >2) had lower suPAR levels than those without proteinuria (2380 pg/ml [2116-2571] versus 3125 pg/ml [2516-4198], respectively; P<0.001). This trend was not seen among male participants; suPAR levels in all female participants were lower than in male participants (P=0.03). Thirty-four patients studied were kidney transplant recipients; transplant status was not associated with suPAR levels in patients with FSGS or non-FSGS diagnoses, independent of proteinuria, race, or sex (P>0.05). CONCLUSIONS On the basis of these results, circulating suPAR is unlikely the leading cause for childhood idiopathic FSGS.

Heritability and Environmental Factors Affecting Vitamin D Status in Rural Chinese Adolescent Twins

CONTEXT Factors associated with the high prevalence of vitamin D deficiency in China are not well described, especially among Chinese adolescents. OBJECTIVES The aim of the study was to examine important environmental or sociodemographic factors influencing 25-hydroxyvitamin D [25(OH)D] levels and estimate its heritability. DESIGN A sample of 226 male and female adolescent twins aged 13-20 yr from a large prospective twin cohort of rural Chinese children and adolescents that has been followed for 6 yr were evaluated. MAIN OUTCOME MEASURE(S) Blood level of 25(OH)D was measured using tandem mass spectrometry methodology. RESULTS The overall mean (SD) 25(OH)D level was 18.0 (9.4) ng/ml, with wide variation by gender and season. In males (47.4% of subjects), the mean (SD) 25(OH)D level was 12.1 (4.2) ng/ml in non-summer and 27.4 (8.8) ng/ml in summer; in females, it was 10.1 (4.1) ng/ml in non-summer and 19.5 (6.3) ng/ml in summer. A multivariate model that included gender, age, season, physical activity, and student status demonstrated that male gender, summer season, and high physical activity significantly increased 25(OH)D levels. Summer season and male gender also significantly decreased the risk of being in the lowest 25(OH)D tertile. Overall, 68.9% of the variability in 25(OH)D level was attributable to additive genetic influence. Stratification by gender found that in males, 85.9% of the variability in 25(OH)D level was attributable to such influence, but in females, it was only 17%. CONCLUSION In this sample of rural Chinese adolescents, 25(OH)D level was influenced by gender, season, and physical activity level. There was a strong genetic influence on 25(OH)D level in males only.

Vitamin D Deficiency in Children With Chronic Kidney Disease: Uncovering an Epidemic

BACKGROUND. Vitamin D deficiency in children adversely affects bone development by reducing mineralization. Children with chronic kidney disease are at risk for altered bone development from renal osteodystrophy and concomitant vitamin D deficiency. The pediatric Kidney Disease Outcomes Quality Initiative guidelines suggest measuring serum 25-hydroxyvitamin D (25[OH]D) levels if serum parathyroid hormone levels are above the target range for chronic kidney disease stages 2 and beyond, but the magnitude of vitamin D deficiency in children with chronic kidney disease is not well studied. OBJECTIVES. The purpose of this work was to determine whether children with chronic kidney disease had vitamin D deficiency, to evaluate whether the prevalence of vitamin D deficiency changed over time, and to examine seasonal and ethnic differences in 25(OH)D levels. METHODS. 25(OH)D levels in children with chronic kidney disease (stages 1–5) were measured over a 10-year period from 1987 to 1996. Data were also collected for a contemporary group of patients from 2005 to 2006. RESULTS. The prevalence of vitamin D deficiency ranged from 20% to 75% in the decade studied. There was a significant trend for decreasing 25(OH)D levels over the decade, both at the group and individual levels. Seasonal variation was noted. In our contemporary population with chronic kidney disease, the mean 25(OH)D level was 21.8 ng/mL; we found a prevalence of vitamin D deficiency of 39%. Black and Hispanic patients had lower levels of 25(OH)D than white patients. CONCLUSIONS. Children with chronic kidney disease have great risk for vitamin D deficiency, and its prevalence was increasing yearly in the studied decade. Contemporary data show that vitamin D deficiency remains a problem in these children. Sunlight exposure and ethnicity play a role in levels of 25(OH)D. Our data support the recent pediatric Kidney Disease Outcomes Quality Initiative guidelines for measurement of 25(OH)D levels in children with chronic kidney disease and secondary hyperparathyroidism.

Maternal Obesity and Vitamin D Sufficiency Are Associated with Cord Blood Vitamin D Insufficiency

CONTEXT An inverse relationship between total serum 25-hydroxyvitamin D (25-OH D) and increased adiposity has been established in children, adolescents, and adults. However, the relationship between neonatal adiposity and vitamin D status has not been reported. Both maternal obesity and vitamin D deficiency in pregnancy are common and are associated with adverse pregnancy outcomes. OBJECTIVE The aim of the study was to determine the relationship between vitamin D levels in mothers and newborns, as influenced by maternal obesity, and evaluate these associations with neonatal adiposity. DESIGN, SETTING, AND PATIENTS Sixty-one maternal-neonatal pairs participated in this cross-sectional study at an academic medical center. Mothers had a prepregnancy body mass index that was normal or obese. OUTCOME MEASURES Maternal and cord blood sera were assayed for 25-OH D, and neonatal body composition was measured by air displacement plethysmography. RESULTS Mothers had similar and sufficient levels of 25-OH D when measured at 36-38 wk gestation, irrespective of body mass index category (normal weight, 46.05, vs. obese, 49.84 ng/ml; P = not significant). However, cord blood 25-OH D was higher in neonates of normal-weight mothers compared to neonates of obese mothers (27.45 vs. 20.81 ng/ml; P = 0.02). The variance in cord blood 25-OH D was explained by four factors: maternal 25-OH D level, the presence of maternal obesity, maternal age, and neonatal adiposity (r(2) = 0.66). CONCLUSION Obese women transfer less 25-OH D to offspring than normal-weight women, despite similar serum levels. Cord blood 25-OH D levels directly correlate to neonatal percentage body fat. These novel findings underscore the evolving relationships between maternal obesity, vitamin D nutritional status, and adiposity in the neonatal period that may influence subsequent childhood and adulthood vitamin D-dependent processes.

Methylated arginine derivatives in children and adolescents with chronic kidney disease

Asymmetric dimethylarginine (ADMA), a methylated L-arginine (Arg) derivative is associated with endothelial dysfunction, vasoconstriction, and hypertension in animals and humans. We examined the relationship between these derivatives, estimated glomerular filtration rate (eGFR), and awake (AW) and asleep (AS) blood pressure (BP) load in children and adolescents (n = 28) with stage 2–3 chronic kidney disease (CKD) and in matched intra-familial controls (n = 10). Plasma L-Arg, ADMA, and symmetric dimethylarginine (SDMA) levels were measured by high-performance liquid chromatography–tandem mass spectrometry. Subjects wore a 24-hr ambulatory BP monitor with BP load >95th percentile. ADMA, SDMA/ADMA ratio and SDMA were 38–200% higher in CKD patients while L-Arg/ADMA and L-Arg/SDMA ratios and the L-Arg level were 11–64% lower. The eGFR explained 42–60% of L-Arg/SDMA, SDMA/ADMA, and SDMA variability (n = 38). Using linear regression, SDMA and SDMA/ADMA separately explained 15–38% of AW and AS systolic (S) BP and diastolic (D) BP load variability (p < 0.001–0.022). Using multivariate stepwise regression with eGFR held constant, SDMA/ADMA was a significant independent variable for AW DBP load (p = 0.03). In conclusion, BP load and a disproportionate elevation of SDMA are seen in children and adolescents with stage 2–3 (mild–moderate) CKD. SDMA is a strong marker for reduced eGFR and serves as a moderate but significant indicator of 24-hr BP load variability.

Longitudinal trajectory of vitamin D status from birth to early childhood in the development of food sensitization

Background:Increasing evidence supports the immunomodulatory effect of vitamin D on allergic diseases. The combined role of prenatal and postnatal vitamin D status in the development of food sensitization (FS) and food allergy remains understudied.Methods:Plasma 25-hydroxyvitamin D (25(OH)D) levels of 460 children in the Boston Birth Cohort (BBC) were measured at birth and early childhood, and the subjects were genotyped for rs2243250 (C-590T) in the IL4 gene. We defined FS as specific IgE levels of ≥0.35 kUA/l to any of eight common food allergens; we defined persistently low vitamin D status as cord blood 25(OH)D <11 ng/ml and postnatal 25(OH)D <30 ng/ml.Results:We observed a moderate correlation between cord blood 25(OH)D at birth and venous blood 25(OH)D measured at 2–3 y (r = 0.63), but a weak correlation at <1 y (r = 0.28). There was no association between low vitamin D status and FS at any single time point alone. However, in combination, persistence of low vitamin D status at birth and in early childhood increased the risk of FS (odds ratio (OR) = 2.03, 95% confidence interval (CI): 1.02–4.04), particularly among children carrying the C allele of rs2243250 (OR = 3.23, 95% CI: 1.37–7.60).Conclusion:Prenatal and early postnatal vitamin D levels, along with individual genetic susceptibility, should be considered in assessing the role of vitamin D in the development of FS and food allergy.