Search

Unlabelled: A comparison of the association of different forms of 25-hydroxyvitamin D [25(OH)D] with parathyroid hormone (PTH) and with areal and volumetric bone mineral density (BMD) demonstrated that bioavailable and free 25(OH)D do not provide a better index of vitamin D status in terms of bone health compared to total 25(OH)D., Introduction: This study aims to compare measures of vitamin D-binding protein (DBP) using a monoclonal versus polyclonal ELISA and assess correlations of total versus estimated free and bioavailable 25(OH)D with BMD and PTH concentrations., Methods: DXA and peripheral quantitative CT (pQCT) scans were obtained in 304 adults (158 black, 146 white), ages 21-80 years. Free and bioavailable 25(OH)D were calculated from total 25(OH)D, DBP, and albumin concentrations. Multivariable linear regression with standardized beta coefficients was used to evaluate associations of bone measures and PTH with total, free, and bioavailable 25(OH)D., Results: Measures of DBP obtained using a monoclonal versus polyclonal ELISA were not correlated (r s = 0.02, p = 0.76). Free and bioavailable 25(OH)D based on the polyclonal assay were lower in black versus white participants (p < 0.0001); this race difference was not evident using the monoclonal assay. Adjusted for age, sex, calcium intake, and race, all forms of 25(OH)D were negatively associated with PTH, but the absolute coefficient was greatest for total 25(OH)D (-0.34, p < 0.001) versus free/bioavailable 25(OH)D (-0.18/-0.24 depending on DBP assay, p ≤ 0.003). In analyses stratified on race, none of the measures of 25(OH)D were associated with BMD across DXA and pQCT sites., Conclusions: The monoclonal versus polyclonal ELISA yielded highly discrepant measures of DBP, particularly among black individuals, likely related to established race differences in DBP polymorphisms. Contrary to prior studies, our findings indicate that using DBP to estimate bioavailable and free 25(OH)D does not provide a better index of vitamin D status in terms of bone health.

Context: Preclinical studies suggest that TNF-α suppresses PTH synthesis, inhibits renal 1α-hydroxylase activity, and impairs fibroblast growth factor 23 (FGF23) degradation. The impact of inflammation on vitamin D and mineral metabolism has not been well-characterized in Crohn's disease (CD)., Objective: The objective of the study was to assess short-term changes in vitamin D-related mineral metabolism in CD after anti-TNF-α induction therapy., Design/participants: Eighty-seven CD participants, aged 5-39 years, were assessed at the initiation of anti-TNF-α therapy and 10 weeks later., Outcomes: Indices of clinical disease activity and serum concentrations of vitamin D metabolites, vitamin D-binding protein (DBP), calcium, PTH, FGF23, IL-6, and TNF-α were measured at each visit. A multivariable generalized estimating equation (GEE) regression analysis was used to examine the correlates of PTH and 1,25-dihydroxyvitamin D [1,25(OH)2D] concentrations at each visit., Results: After anti-TNF-α therapy, cytokines and inflammatory markers [IL-6, TNF-α, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP)] concentrations decreased (all P < .0001), and PTH and 1,25(OH)2D concentrations increased (median 21 vs 30 pg/mL, P < .0001, and median 41.7 vs 48.1 pg/mL, P = .014, respectively). Levels of 25-hydroxyvitamin D [25(OH)D], 24,25-dihydroxyvitamin D, DBP, and FGF23 did not change. In GEE analyses, higher IL-6, TNF-α, ESR, and CRP were associated with lower PTH concentrations (all P < .001), adjusted for corrected calcium and 25(OH)D levels. Higher PTH was associated with higher 1,25(OH)2D concentrations (P < .001) at each visit, independent of 25(OH)D concentrations. Higher levels of all inflammatory markers were associated with lower 1,25(OH)2D concentrations (all P < .05). However, when PTH was added to these models, the inflammatory markers (with the exception of CRP) were no longer significantly associated with 1,25(OH)2D., Conclusions: Greater inflammation was associated with lower PTH and 1,25(OH)2D concentrations. After anti-TNF-α induction, PTH and 1,25(OH)2D concentrations increased without concomitant changes in 25(OH)D and FGF23, consistent with effects of inflammation on PTH and thereby renal conversion of 25(OH)D to 1,25(OH)2D.

Objective: This study examined rates and determinants of vitamin D supplementation among Chronic Renal Insufficiency Cohort (CRIC) participants and determined the association between dose and 25-hydroxyvitamin D (25(OH)D) level. The 2010 Institute of Medicine Report noted a significant increase in vitamin D supplementation in the general population, but use in chronic kidney disease (CKD) is unknown., Methods: CRIC is a multicenter prospective observational cohort study of 3,939 participants with a median baseline age of 60 and an estimated glomerular filtration rate (eGFR) of 42.1 mL/minute per 1.73 m2. Of the cohort, 54.9% was male, 42.1% were Black, and 48.4% were diabetic. Multivariable logistic generalized estimating equations were used to examine determinants of supplementation use assessed annually between 2003 and 2011. Cross-sectional linear regression models, based on a subset of 1,155 participants, assessed associations between supplement dose and 25(OH)D level, measured by high-performance liquid chromatography coupled with tandem mass spectrometry., Results: The proportion of participants reporting supplement use increased (P < .0001), from 10% at baseline to 44% at 7-year follow-up visits. This was largely due to initiation of products containing only ergocalciferol or cholecalciferol. The odds of supplementation were greater in older, female, non-Black, married participants with greater education and lower body mass index. Among participants taking supplementation, dose was positively associated with 25(OH)D level, adjusted for race, season, diabetes, dietary intake, eGFR, and proteinuria. Only 3.8% of non-Black and 16.5% of Black participants taking a supplement were deficient (<20 ng/mL), whereas 22.7% of non-Black and 62.4% of black participants not reporting supplement use were deficient., Conclusions: Vitamin D supplementation rates rose significantly among CRIC participants over 7 years of follow-up and were associated with greater serum 25(OH)D levels. Studies of vitamin D levels on clinical outcomes in CKD and future vitamin D interventional studies should consider these changes in supplementation practices., (Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Vitamin D-binding protein (DBP) and catabolism have not been examined in the clinical setting of childhood chronic kidney disease (CKD)., Methods: The concentrations of serum vitamin D {25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)(2)D], 24,25-dihydroxyvitamin D [24,25(OH)(2)D]}, DBP, intact parathyroid hormone (iPTH), and fibroblast growth factor-23 (FGF23) were measured in 148 participants with CKD stages 2-5D secondary to congenital anomalies of the kidney/urinary tract (CAKUT), glomerulonephritis (GN), or focal segmental glomerulosclerosis (FSGS). Free and bioavailable 25(OH)D concentrations were calculated using total 25(OH)D, albumin, and DBP concentrations., Results: The concentrations of all vitamin D metabolites were lower with more advanced CKD (p < 0.001) and glomerular diagnoses (p ≤ 0.002). Among non-dialysis participants, DBP was lower in FSGS versus other diagnoses (FSGS-dialysis interaction p = 0.02). Winter season, older age, FSGS and GN, and higher FGF23 concentrations were independently associated with lower concentrations of free and bioavailable 25(OH)D. Black race was associated with lower total 25(OH)D and DBP, but not free or bioavailable 25(OH)D. 24,25(OH)(2)D was the vitamin D metabolite most strongly associated with iPTH. Lower 25(OH)D and higher iPTH concentrations, black race, and greater CKD severity were independently associated with lower levels of 24,25(OH)(2)D, while higher FGF23 concentrations and GN were associated with higher levels of 24,25(OH)(2)D., Conclusions: Children with CKD exhibit altered catabolism and concentrations of DBP and free and bioavailable 25(OH)D, and there is an important impact of their underlying disease.

Background: Vitamin D deficiency may contribute to risk of cardiovascular disease, diabetes, and infections, in addition to known effects on mineral metabolism. Controversy remains regarding the use of nutritional vitamin D supplementation in chronic kidney disease (CKD), and the supplementation practices of pediatric nephrologists are unknown., Methods: An electronic survey containing eight vignettes was sent to physician members of the International Pediatric Nephrology Association in 2011 to identify physician and patient characteristics that influence nephrologists to supplement CKD patients with nutritional vitamin D. Vignettes contained patient characteristics including light vs dark skin, CKD stage, cause of renal disease, parathyroid hormone (PTH), and 25(OH) vitamin D levels. Multivariate logistic generalized estimating equation regression was used to identify predictors of supplementation., Results: Of 1,084 eligible physicians, 504 (46%) completed the survey. Supplementation was recommended in 73% of cases overall (ranging from 91% of those with vitamin D levels <10 ng/mL to 35% with levels >30). Greater CKD severity was associated with greater recommendation of supplementation, especially for patients with higher vitamin D levels (test for interaction p < 0.0001). PTH level above target for CKD stage was associated with greater recommendation to supplement in pre-dialysis CKD, but did not have an impact on recommendations in dialysis patients (test for interaction p < 0.0001). Skin color, cause of CKD, and albumin levels were not associated with supplementation recommendation., Conclusions: Recommending nutritional vitamin D is common worldwide, driven by CKD stage and vitamin D and PTH levels. Future studies are needed to establish the risks and benefits of supplementation.

Background: Prior studies of vitamin D metabolism in Crohn's disease (CD) did not include controls or examine changes following diagnosis. This study examined associations among 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)(2)D], and parathyroid hormone (PTH) levels in incident pediatric CD, compared with controls, and following diagnosis., Methods: Serum vitamin D and PTH were measured at diagnosis (n = 78), 6, 12, and a median of 43 months (n = 52) later in CD participants, and once in 221 controls. Multivariate regression was used to examine baseline associations and quasi-least squares regression to assess subsequent changes., Results: At diagnosis, 42% of CD participants were 25(OH)D-deficient (<20 ng/mL). The odds ratio for deficiency was 2.1 (95% confidence interval [CI]: 1.1, 3.9; P < 0.05) vs. controls, adjusted for age, race, and season. 1,25(OH)(2)D was lower in CD vs. controls (P < 0.05), adjusted for 25(OH)D, tumor necrosis factor alpha (TNF-α), and PTH. TNF-α was associated with lower 1,25(OH)(2)D (P < 0.05), and the positive association between PTH and 1,25(OH)(2)D in controls was absent in CD (interaction P = 0.02). Among participants with 25(OH)D <30 ng/mL, CD was associated with lower PTH (P < 0.05) vs. controls. Following diagnosis, 25(OH)D and 1,25(OH)(2)D improved (P < 0.001). At the final visit, 3% were 25(OH)D-deficient, PTH was no longer low relative to 25(OH)D, and 1,25(OH)(2)D was significantly elevated (P < 0.001) compared with controls., Conclusions: Incident CD was associated with 25(OH)D and 1,25(OH)2D deficiency and a relative hypoparathyroidism that resolved following diagnosis. Inflammatory cytokine suppression of PTH and renal 1-α-hyroxylase may contribute to these alterations.

Objectives: Vitamin D deficiency is a potential risk factor for autoimmunity. Prior studies of the association between vitamin D levels and rheumatoid arthritis (RA) disease activity have yielded conflicting results., Methods: Serum 25(OH)vitamin D levels were measured at baseline in 499 participants with active RA, ages 18-85 years, enrolled in a randomised clinical trial of golimumab (Go-Before Trial). Subjects were methotrexate and biologic therapy naïve. Multivariable linear regression was used to assess associations between vitamin D levels and disease activity scores (DAS28), van der Heijde-Sharp (vdHS) erosion scores, and serum inflammatory markers. Generalised estimating equations were used to evaluate the associations between vitamin D status and the response to therapy over 52 weeks, using the DAS28 and ACR response., Results: Forty-eight percent of participants were vitamin D deficient, defined as serum 25(OH)vitamin D <20 ng/mL. Deficiency was not associated with greater DAS28 (β-0.021 [95% CI -0.22, 0.18]), adjusted for age, race, sex, BMI, disease duration and glomerular filtration rate. Vitamin D deficiency was not associated with baseline vdHS scores or inflammatory markers in adjusted or unadjusted models. There was no association between baseline vitamin D deficiency and change in DAS28 (β = -0.024 [-0.30, 0.25]), proportion meeting ACR response (OR 0.82 [0.56, 1.20]), or radiographic progression at 52 weeks (OR 0.91 [0.59-1.40])., Conclusions: Vitamin D levels were not associated with RA disease activity, inflammatory markers, or vdHS scores at baseline. Furthermore, there was no association between baseline vitamin D level and response to therapy or radiographic progression.

Background: Vitamin D deficiency is associated with fractures, infections and death. Liver disease impairs vitamin D and vitamin D binding protein (DBP) metabolism., Aims: We aimed to determine the impact of liver transplantation on vitamin D, particularly on DBP and free vitamin D concentrations., Methods: Serum 25(OH)D, 1,25(OH)(2) D and DBP concentrations were measured in 202 adults before liver transplantation and 3 months later in 155. Free vitamin D concentrations were estimated from these values. Risk factors for 25(OH)D deficiency (<20 ng/ml) and low 1,25(OH)(2) D (<20 pg/ml) were examined with logistic regression, and changes in concentrations following transplantation with linear regression., Results: Pretransplant, 84% were 25(OH)D deficient, 13% had 25(OH)D concentrations <2.5 ng/ml, and 77% had low 1,25(OH)(2) D. Model for end-stage liver disease score ≥ 20 (P < 0.005) and hypoalbuminemia (P < 0.005) were associated with low 25(OH)D and 1,25(OH)(2) D concentrations. Following transplantation, 25(OH)D concentrations increased a median of 17.8 ng/ml (P < 0.001). Albumin increased from a median of 2.7 to 3.8 g/dl (P < 0.001) and DBP from 8.6 to 23.8 mg/dl (P < 0.001). Changes in total 25(OH)D were positively and independently associated with changes in DBP (P < 0.05) and albumin (P < 0.001). Free 25(OH)D concentrations rose from 6.0 to 9.7 pg/ml (P < 0.001). In contrast, total 1,25(OH)(2)D concentrations rose only by 4.3 pg/ml (P < 0.001) and free 1,25(OH)(2D concentrations declined (P < 0.001)., Conclusions: Serum total and free 25(OH)D and DBP concentrations rose substantially following transplantation, while 1,25(OH)(2) D concentrations showed modest changes and free 1,25(OH)(2) D decreased. Studies of the effects of vitamin D status on diverse transplant complications are needed., (© 2011 John Wiley & Sons A/S.)

The objectives were to determine the prevalence of vitamin D deficiency [25(OH)D < 10 ng/ml] in pediatric renal transplant (RTx) recipients, compared with controls and identify correlates of changes in 25(OH)D and intact parathyroid hormone (iPTH) levels following transplantation. Serum 25(OH)D, 1,25(OH)(2)D, and iPTH were measured once in 275 healthy controls and at transplantation, and 3 and 12 months posttransplantation in 58 RTx recipients. Multivariate logistic regression models determined the odds ratio (OR) of vitamin D deficiency in RTx recipients vs. controls adjusted for age, sex, race, and season. Generalized estimating equations were used to assess changes following transplantation. At transplantation, 22% of nonblack and 27% of black RTx recipients were vitamin D deficient. The adjusted OR of vitamin D deficiency was greater in RTx recipients (p < 0.001) compared with controls; however, the transplant association was greater in nonblack vs. black individuals (interaction p = 0.02). Overall, 25(OH)D levels did not change significantly following transplantation. Younger age (p < 0.01), nonblack race (p < 0.001), visits in nonwinter months (p < 0.001), and supplementation with ≥400 IU/day ergo/cholecalciferol (p < 0.001) were associated with increases (or lesser declines) in 25(OH)D following transplantation. Increases in 25(OH)D levels (p < 0.001) and vitamin D supplementation (p < 0.01) were associated with greater reductions in iPTH levels following transplantation, independent of 1,25(OH)(2)D levels.

Background: Serum 25-hydroxyvitamin D [25(OH)D] concentrations serve as a biomarker for vitamin D stores. Prior studies have not examined the risk factors for low vitamin D concentrations in a multiethnic sample of US youth across a broad age range., Objective: The objective was to determine the prevalence of and factors associated with low concentrations of 25(OH)D in children and adolescents., Design: Serum 25(OH)D concentrations were measured in 382 healthy children aged 6-21 y living in the northeastern United States. Dietary and supplemental vitamin D intake was assessed by interview. Fat and lean mass were assessed by dual-energy X-ray absorptiometry. Multivariable ordinal logistic regression was used to determine factors associated with decreased concentrations of 25(OH)D., Results: The median concentration of 25(OH)D was 28 ng/mL (interquartile range: 19-35 ng/mL), and 55% of subjects had 25(OH)D concentrations <30 ng/mL. 25(OH)D concentrations were inversely correlated with parathyroid hormone concentrations (Spearman's r=-0.31, P<0.001) but were not significantly correlated with 1,25-dihydroxyvitamin D concentrations. In the multivariable model, older age (P<0.001), black race [odds ratio (OR): 14.2; 95% CI: 8.53, 23.5], wintertime study visit (OR: 3.55; 95% CI: 2.29, 5.50), and total daily vitamin D intake <200 IU (OR: 1.58; 95% CI: 1.02, 2.46) were associated with low vitamin D concentrations. Fat and lean mass were not independently associated with vitamin D status in this healthy-weight sample., Conclusion: Low serum 25(OH)D concentrations are prevalent in otherwise healthy children and adolescents in the northeastern United States and are related to low vitamin D intake, race, and season.

Serum 25-hydroxyvitamin D [25(OH)D] concentrations are the best indicator of vitamin D nutritional status. We measured serum 25(OH)D concentrations in 94 healthy controls and in 41 subjects (aged 4-22 years) with steroid-sensitive nephrotic syndrome (SSNS) in remission. Children with remitted SSNS had significantly lower 25(OH)D concentrations than healthy controls (median 16.4 ng/ml versus 23.9 ng/ml, P<0.001). In a multivariable logistic regression model, the odds ratios (OR) of vitamin D insufficiency [25(OH)D <20 ng/ml] were independently increased in SSNS subjects [OR 11.2 (95% confidence interval 3.5-36.2)], non-whites [OR 12.9 (4.6-36.2)], older children [OR 1.20 per year (1.06-1.36)], and winter months [OR 6.7 (2.5-18.4)]. Within the SSNS subjects, multiple linear regression determined that serum 25(OH)D concentrations were not associated with SSNS disease characteristics measured in this study, such as duration of disease, number of relapses, cumulative glucocorticoids, and interval since last relapse. In conclusion, children with remitted SSNS have lower serum 25(OH)D concentrations than healthy controls. This difference persisted after adjusting for the potential confounding effects of age, race, season, and milk intake. Children with remitted SSNS may benefit from routine measurement of 25(OH)D, but the clinical significance of low 25(OH)D in this population remains unclear.

Summary: A comparison of the association of different forms of 25-hydroxyvitamin D [25(OH)D] with parathyroid hormone (PTH) and with areal and volumetric bone mineral density (BMD) demonstrated that bioavailable and free 25(OH)D do not provide a better index of vitamin D status in terms of bone health compared to total 25(OH)D. Introduction: This study aims to compare measures of vitamin D-binding protein (DBP) using a monoclonal versus polyclonal ELISA and assess correlations of total versus estimated free and bioavailable 25(OH)D with BMD and PTH concentrations. Methods: DXA and peripheral quantitative CT (pQCT) scans were obtained in 304 adults (158 black, 146 white), ages 21-80 years. Free and bioavailable 25(OH)D were calculated from total 25(OH)D, DBP, and albumin concentrations. Multivariable linear regression with standardized beta coefficients was used to evaluate associations of bone measures and PTH with total, free, and bioavailable 25(OH)D. Results: Measures of DBP obtained using a monoclonal versus polyclonal ELISA were not correlated ( r = 0.02, p = 0.76). Free and bioavailable 25(OH)D based on the polyclonal assay were lower in black versus white participants ( p < 0.0001); this race difference was not evident using the monoclonal assay. Adjusted for age, sex, calcium intake, and race, all forms of 25(OH)D were negatively associated with PTH, but the absolute coefficient was greatest for total 25(OH)D (−0.34, p < 0.001) versus free/bioavailable 25(OH)D (−0.18/−0.24 depending on DBP assay, p ≤ 0.003). In analyses stratified on race, none of the measures of 25(OH)D were associated with BMD across DXA and pQCT sites. Conclusions: The monoclonal versus polyclonal ELISA yielded highly discrepant measures of DBP, particularly among black individuals, likely related to established race differences in DBP polymorphisms. Contrary to prior studies, our findings indicate that using DBP to estimate bioavailable and free 25(OH)D does not provide a better index of vitamin D status in terms of bone health. [ABSTRACT FROM AUTHOR]