MO42825-HYDROXYVITAMIN D AND TUBULAR DYSTROPHY IN PATIENTS WITH CKD STAGES 1-3*

Background and Aims According to a recent data the 25-hydroxyvitamin D (25OHD) level is known to be reduced in advanced stages of CKD presumably due to i) catabolic activity of CYP24 in damaged tubules and ii) increase in renal excretion of 25OHD/Vitamin D binding protein complex. The association of the 25OHD level with different types of tubular damage in early stages (1-3) of CKD is not well investigated. Method The cross-sectional study included 100 patients (37 male; age 38 (30-50) yrs.) with biopsy proven primary glomerulopathy (membranoproliferative glomerulonephritis (n=9); minimal change disease (n=10); membranous nephropathy (n=11); focal segmental glomerulosclerosis (n=20); IgA nephropathy (n=50)) and CKD stages 1-3 (median eGFR was 64 (33-90) ml/min/1.73 m2). Patients with AKI, infectious diseases, heart failure, respiratory failure and cancer pathology were excluded. The levels of proteinuria, intact parathyroid hormone (PTH) (Beckman Coulter), 25OHD (Abbott) were estimated in all patients. In all cases the following types of tubular damage were analyzed by light microscopy of kidney tissue (hematoxylin and eosin, periodic acid Schiff, Masson's trichrome, Congo red, and Jones' silver) and calculated semi-quantitatively (0 – <10%; 1 – 10-25%; 2 – 26-50% and 3 – >50% of tissue sample): granular dystrophy, hyaline-drop dystrophy, hydropic dystrophy, foamy degeneration and atrophy. The association between clinical and morphological variables was estimated by Spearman’s coefficient and multiple linear regression analysis. Results The patients had a lack or deficiency of 25OHD [Me (Q1-Q3): 13.1 (7.6-19.3) ng/ml]. There was no correlation between serum 25OHD and PTH (r = -0.03, p = 0.86). Proteinuria was negatively associated with level of 25OHD (r = -0.56, p = 0.012). The level of 25OHD was associated with granular (r = -0.39, p <0.05) and hyaline-drop (r = -0.39, p <0.05) tubular dystrophy. In multiple regression analysis the 25OHD level was the independent predictor of the severe hyaline-drop tubular dystrophy (β = -0.33 ± 0.11, p = 0.046) when adjusted for proteinuria (β=0.22±0.11, p=0.062). Conclusion In patients with CKD stages 1-3 decline in serum 25OHD is associated with the severity of tubular dystrophy. 25OHD level may be useful in laboratory diagnosis as a risk factor of tubular damage in early stages of CKD.

The Sun’s Vitamin in Adult Patients Affected by Prader–Willi Syndrome

Prader–Willi syndrome (PWS) is a genetic disorder characterized by hyperphagia with progressive, severe obesity, and an increased risk of obesity-related comorbidities in adult life. Although low dietary vitamin D intake and low 25-hydroxy vitamin D (25OHD) levels are commonly reported in PWS in the context of bone metabolism, the association of low 25OHD levels with fat mass has not been extensively evaluated in PWS adults. The aims of this study were to investigate the following in PWS adults: (1) 25OHD levels and the dietary vitamin D intake; (2) associations among 25OHD levels with anthropometric measurements and fat mass; (3) specific cut-off values for body mass index (BMI) and fat mass predictive of the 25OHD levels. In this cross-sectional, single-center study we enrolled 30 participants, 15 PWS adults (age 19–41 years and 40% males) and 15 control subjects matched by age, sex, and BMI from the same geographical area (latitude 40° 49’ N; elevation 17 m). Fat mass was assessed using a bioelectrical impedance analysis (BIA) phase-sensitive system. The 25OHD levels were determined by a direct competitive chemiluminescence immunoassay. Dietary vitamin D intake data was collected by three-day food records. The 25OHD levels in the PWS adults were constantly lower across all categories of BMI and fat mass compared with their obese counterpart. The 25OHD levels were negatively associated with BMI (p = 0.04), waist circumference (p = 0.03), fat mass (p = 0.04), and dietary vitamin D intake (p < 0.001). During multiple regression analysis, dietary vitamin D intake was entered at the first step (p < 0.001), thus explaining 84% of 25OHD level variability. The threshold values of BMI and fat mass predicting the lowest decrease in the 25OHD levels were found at BMI ≥ 42 kg/m2 (p = 0.01) and fat mass ≥ 42 Kg (p = 0.003). In conclusion, our data indicate that: (i) 25OHD levels and dietary vitamin D intake were lower in PWS adults than in the control, independent of body fat differences; (ii) 25OHD levels were inversely associated with BMI, waist circumference, and fat mass, but low dietary vitamin D intake was the major determinant of low vitamin D status in these patients; (iii) sample-specific cut-off values of BMI and fat mass might help to predict risks of the lowest 25OHD level decreases in PWS adults. The presence of trained nutritionists in the integrated care teams of PWS adults is strongly suggested in order to provide an accurate nutritional assessment and tailored vitamin D supplementations.

Serum vitamin D deficiency in children and adolescents is associated with type 1 diabetes mellitus

Background To investigate the relationship 25-hydroxy vitamin D (25OHD) level among children and in children with type 1 diabetes mellitus (T1DM). Methods A case–control study was conducted to compare the serum 25OHD levels between cases and controls. This study recruited 296 T1DM children (106 newly diagnosed T1DM patients and 190 established T1DM patients), and 295 age- and gender-matched healthy subjects as controls. Results The mean serum 25OHD in T1DM children was 48.69 ± 15.26 nmol/L and in the controls was 57.93 ± 19.03 nmol/L. The mean serum 25OHD in T1DM children was lower than that of controls (P < 0.01). The mean serum 25OHD level (50.42 ± 14.74 nmol/L) in the newly diagnosed T1DM children was higher than that (47.70 ± 15.50 nmol/L) in the established T1DM children but the difference was not statistically significant (P = 0.16). HbA1c values were associated with 25OHD levels in established T1DM children (r = 0.264, P < 0.01), and there was no association between 25OHD and HbA1c in newly diagnosed T1DM children (r = 0.164; P > 0.05). Conclusion Vitamin D deficiency is common in T1DM children, and it should be worthy of attention on the lack of vitamin D in established T1DM children.

Effect of Simvastatin and Atorvastatin on Serum Vitamin D and Bone Mineral Density in Hypercholesterolemic Patients: A Cross-Sectional Study

Background. Besides lipid-lowering effect of statins, they have been shown to have nonlipid lowering effects, such as improving bone health. An improvement in bone mineral density (BMD) has been indicated in some studies after the use of statins, in addition to an increase in 25-hydroxyvitamin D (25OHD) level. The aim of this study is to explore the association between statins and bone health taking into consideration 25OHD level and BMD.Methods. This is a randomized, cross-sectional comparative study. Subjects were divided into two groups, hypercholesterolemic participants taking simvastatin or atorvastatin as the study group and a matched control group not taking statins. All participants were assessed for serum 25OHD and BMD at lumbar spine and femoral neck.Results. A total of 114 participants were included in the study, 57 participants in each group. Results of serum 25OHD showed no significant difference between study and control groups (P=0.47), while BMD results of lumbar spine and femoral neck showed significant difference (P=0.05and 0.03, resp.).Conclusion. Simvastatin and atorvastatin, at any dose for duration of more than one year, have no additive effect on 25OHD level but have a positive effect on the BMD.

Vitamin D nutritional status in preterm infants and response to supplementation

Little is known about vitamin D status in preterm infants and their response to supplementation. To investigate this, we assessed serum 25-hydroxyvitamin D (25OHD) levels using RIA in a consecutive sample of stable preterm very low birth weight (VLBW) infants (born ≤ 32 weeks gestation or birth weight ≤ 1·5 kg), and we explored associated factors. Serum 25OHD level was first assessed once infants were tolerating feeds (n 274). If this first 25OHD level was below 50 nmol/l (20 ng/ml), which is the level associated with covering requirements in terms of skeletal health in the majority, then we recommended prolonged augmented vitamin D intake ( ≥ 10 μg (400 IU) daily) from a combination of fortified feeds and vitamin supplements and follow-up re-assessment at approximately 6 weeks corrected age (n 148). The first assessment, conducted at a median for chronological age of 18 (interquartile range (IQR) 11–28) d, found that 78 % had serum 25OHD levels below 50 nmol/l. Multivariable analysis demonstrated that the determinants of serum 25OHD levels were duration of vitamin D supplementation and gestational age at birth (r2 0·215; P< 0·001). At follow-up, after a median of 104 (IQR 78–127) d, 87 % achieved levels ≥ 50 nmol/l and 8 % had levels >125 nmol/l, a level associated with potential risk of harm. We conclude that low 25OHD levels are an issue for preterm VLBW infants, warranting early nutritional intervention. In infants with serum 25OHD levels < 50 nmol/l, a vitamin D intake of ≥ 10 μg (400 IU) daily achieves target levels in the majority; however, further work is needed to determine the exact dose to safely meet target levels without overcorrection.

Change of serum vitamin D according to the breast cancer treatment.

172 Background: Vitamin D deficiency is associated with increased breast cancer risk and decreased breast cancer survival. The purpose of this study was to determine the effect of breast cancer adjuvant treatment to the vitamin D status, as measured by the serum hydroxyvitamin D (25OHD) in breast cancer patients. Methods: For 589 patients who was diagnosed as a non metastatic breast cancer in 2009 at the asan medical center, blood was prospectively analyzed in batches for serum 25 OHD level at basal and at 6 and 12month. We excluded the patients who took a vitamin D supplementation and got a neoadjuvant chemotherapy. Vitamin D sufficiency was defined as serum as 30ng/ml or greater, insufficiency as 20 to 29 ng/ml and insufficiency as less than 20ng/ml. Results: At baseline, mean serum 25OHD was greater in summer (April to Oct) than Winter (Nov to May ) (28.2ng/ml vs 32.9ng/ml respectively, p=0.000). The patients who did not get a chemotherapy and anti-hormonal therapy as baseline, the patient with chemotherapy showed decreased serum 25OHD level than who without chemotherapy in 6 month but not in 12 month (p=0.003, vs p=0.156 respectively). The patients who had taken anti-hormonal therapy showed significant increasing serum 25OHD in 6 month and 12 months (p=0.000 both). For the patients who got both chemotherapy and anti-hormonal therapy, the changes of serum 25OHD level is smaller than the patients who got a chemotherapy only. For the patients who got a chemotherapy, 57% of patients were vitamin D sufficient at baseline, but 27% of patients in 6 month and 49% in 12 month (p=0.001). Conclusions: Vitamin D status was worse during chemotherapy but recovered after chemotherapy. Antihormonal therapy make the serum vitamin D level increased. The translational research about the effect of chemotherapy and antihormonal therapy to the vitamin D status should be warranted.

Vitamin D levels during and after high-dose vitamin D supplementation in women with early-stage breast cancer

e20561 Background: Experts define vitamin D deficiency as a 25-hydroxyvitamin D (25OHD) level of < 20 ng/ml; a level < 32 ng/ml is considered insufficient for bone health and > 40 ng/ml may be associated with optimum musculoskeletal function and reduced risk for breast cancer. We conducted a study to determine the effect of high dose vitamin D3 at 50,000 IU/wk (HD vitD) on musculoskeletal symptoms from adjuvant letrozole in breast cancer patients. We present here the effectiveness of HD vitD in achieving optimum 25OHD levels and the rate of decline of 25OHD levels after 12 weeks of HD vitD. Methods: The cohort included post-menopausal women with early stage hormone receptor positive breast cancer initiating letrozole treatment. Women with baseline 25OHD levels < 40 ng/ml received 12 weeks of HD vitD. 25OHD levels were assessed at 6 and 12 weeks during HD vitD supplementation and at 3 and 6 months after completing HD vitD but while taking maintenance dose of 600–1000 IU of vitamin D3 daily. Results: 40 women that received HD vitD completed the follow-up phase of the study and are included in this analysis. At entry on study, median 25OHD level was 23 ng/ml; 38% of the women had vitD deficiency, 75% had insufficiency, and 93% had 25OHD levels < 40 ng/ml. Six weeks of HD vitD increased median 25OHD level to 60 ng/ml and another 6 weeks increased it further to 66 ng/ml. With only 6 weeks of HD vitD supplementation, 98% of the women achieved a 25OHD level of > 40 ng/ml. Median 25OHD levels 3 and 6 months after completion of HD vitD were 49 and 40 ng/ml, respectively. The median rate of decrease in vitD levels per month was 6.8% of the level at completion of supplementation. Using linear regression analysis, projected changes in 25OHD levels were calculated for each subject. Median extrapolated time to drop to a 25OHD level of < 40 ng/ml was 6.0 months, to <32 ng/ml was 7.8 months, and to <20 ng /ml was 10.6 months. Conclusions: Supplementation with vitD3 at 50,000 IU/week for 6 weeks is sufficient to achieve a 25OHD level of >40 ng/ml in 98% of postmenopausal women with breast cancer on an AI. After 12 weeks of HD vitD, there is a steady decline in 25OHD levels at a rate of about 7% per month despite continuing on 600 to 1000 IU of D3 daily. Thus, standard doses of D3 are not adequate to maintain 25OHD levels achieved by HD vitD. No significant financial relationships to disclose.