Altered Calcium and Vitamin D Homeostasis in First-Time Calcium Kidney Stone-Formers

Background

Elevated serum 1,25-dihydroxyvitamin D (1,25(OH)₂D) concentrations have been reported among cohorts of recurrent calcium (Ca) kidney stone-formers and implicated in the pathogenesis of hypercalciuria. Variations in Ca and vitamin D metabolism, and excretion of urinary solutes among first-time male and female Ca stone-formers in the community, however, have not been defined.

Methods

In a 4-year community-based study we measured serum Ca, phosphorus (P), 25-hydroxyvitamin D (25(OH)D), 1,25(OH)₂D, 24,25-dihydroxyvitamin D (24,25(OH)₂D), parathyroid hormone (PTH), and fibroblast growth factor-23 (FGF-23) concentrations in first-time Ca stone-formers and age- and gender frequency-matched controls.

Results

Serum Ca and 1,25(OH)₂D were increased in Ca stone-formers compared to controls (P = 0.01 and P = 0.001). Stone-formers had a lower serum 24,25(OH)₂D/25(OH)D ratio compared to controls (P = 0.008). Serum PTH and FGF-23 concentrations were similar in the groups. Urine Ca excretion was similar in the two groups (P = 0.82). In controls, positive associations between serum 25(OH)D and 24,25(OH)₂D, FGF-23 and fractional phosphate excretion, and negative associations between serum Ca and PTH, and FGF-23 and 1,25(OH)₂D were observed. In SF associations between FGF-23 and fractional phosphate excretion, and FGF-23 and 1,25(OH)₂D, were not observed. 1,25(OH)₂D concentrations associated more weakly with FGF-23 in SF compared with C (P <0.05).

Conclusions

Quantitative differences in serum Ca and 1,25(OH)₂D and reductions in 24-hydroxylation of vitamin D metabolites are present in first-time SF and might contribute to first-time stone risk.     

Temporal Relationship between Vitamin D Status and Parathyroid Hormone in the United States

Background

Interpretation of parathyroid hormone (iPTH) requires knowledge of vitamin D status that is influenced by season.

Objective

Characterize the temporal relationship between 25-hydroxyvitamin D₃ levels [25(OH)D₃] and intact iPTH for several seasons, by gender and latitude in the U.S. and relate 25-hydrovitamin D₂ [25(OH)D₂] levels with PTH levels and total 25(OH)D levels.

Method

We retrospectively determined population weekly-mean concentrations of unpaired [25(OH)D₂ and 25(OH)D₃] and iPTH using 3.8 million laboratory results of adults. The 25(OH)D₃ and iPTH distributions were normalized and the means fit with a sinusoidal function for both gender and latitudes: North >40, Central 32–40 and South <32 degrees. We analyzed PTH and total 25(OH)D separately in samples with detectable 25(OH)D₂ (≥4 ng/mL).

Findings

Seasonal variation was observed for all genders and latitudes. 25(OH)D₃ peaks occurred in September and troughs in March. iPTH levels showed an inverted pattern of peaks and troughs relative to 25(OH)D₃, with a delay of 4 weeks. Vitamin D deficiency and insufficiency was common (33% <20 ng/mL; 60% <30 ng/mL) as was elevated iPTH levels (33%>65 pg/mL). The percentage of patients deficient in 25(OH)D₃ seasonally varied from 21% to 48% and the percentage with elevated iPTH reciprocally varied from 28% to 38%. Patients with detectable 25(OH)D₂ had higher PTH levels and 57% of the samples with a total 25(OH)D > 50 ng/mL had detectable 25(OH)D₂.

Interpretation

25(OH)D₃ and iPTH levels vary in a sinusoidal pattern throughout the year, even in vitamin D₂ treated patients; 25(OH)D₃, being higher in the summer and lower in the winter months, with iPTH showing the reverse pattern. A large percentage of the tested population showed vitamin D deficiency and secondary hyperparathyroidism. These observations held across three latitudinal regions, both genders, multiple-years, and in the presence or absence of detectable 25(OH)D₂, and thus are applicable for patient care.     

Effect of Paricalcitol vs Calcitriol on Hemoglobin Levels in Chronic Kidney Disease Patients: A Randomized Trial

Background

Recent studies suggest that vitamin D deficiency represents an additional cofactor of renal anemia, with several mechanisms accounting for this relationship. In line with it, the administration of vitamin D or its analogues has been associated with an improvement of anemia. There are no data, however, about a direct effect of paricalcitol on hemoglobin (Hb) levels. Therefore, we conducted a study to determine whether paricalcitol, compared to calcitriol, improves anemia in patients with chronic kidney disease (CKD).

Methods

In this randomized trial 60 CKD patients stage 3b-5 and anemia (Hb levels: 10-12.5 g/dL) were assigned (1:1) to receive low doses of calcitriol (Group Calcitriol) or paricalcitol (Group Paricalcitol) for 6 months. All the patients had normal values of plasma calcium, phosphorus and PTH, a stable iron balance, and normal values of C-Reactive Protein. The primary endpoint was to evaluate the effects of the two treatments on Hb levels; the modifications in 24hr-proteinuria (UProt) were also evaluated.

Results

A significant Group x Time interaction effect was observed in the longitudinal analysis of Hb levels (F(1,172)=31.4, p<0.001). Subjects in Paricalcitol experienced a significant monthly increase of Hb levels equal to +0.16 g/dL [95% C.I. 0.10 to +0.22, p<0.001) while in Group Calcitriol, Hb decrease throughout the follow-up with an average monthly rate of -0.10 g/dL (95% C.I.: -0.17 to -0.04, p<0.001). In Group Paricalcitol, UProt was significantly reduced after 6 months [0.35 (0.1-1.2) vs 0.59 (0.2-1.6), p<0.01], whereas no significant difference emerged in Group Calcitriol. Plasma levels of calcium, phosphate, PTH and of inflammation markers remained in the normal range in both groups throughout the study.

Conclusions

Short-term exposure to paricalcitol results in an independent increase in Hb levels, which occurred with no modification of iron balance, inflammatory markers, and PTH plasma concentrations, and was associated with a decrease in UProt.

Trial Registration

ClinicalTrials.gov NCT01768351     

1,25-Dihydroxyvitamin D and the Vitamin D Receptor Gene Polymorphism Apa1 Influence Bone Mineral Density in Primary Hyperparathyroidism

Objective

Parathyroid hormone (PTH) and vitamin D are the most important hormones regulating calcium metabolism. In primary hyperparathyroidism (PHPT) excessive amounts of PTH are produced. Bone turnover is enhanced, leading to reduced bone mineral density and elevated levels of serum calcium. The aim of this study was to investigate relations between serum levels of 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)₂D) and bone mineral density, as well as known genetic polymorphisms in the vitamin D receptor and enzymes metabolising vitamin D in patients with PHPT.

Design/Subjects

We conducted a cross-sectional study of 52 patients with PHPT.

Results

Mean level of 25(OH)D was 58.2 nmol/L and median 1,25(OH)₂D level was 157 pmol/L. Among our patients with PHPT 36.5% had 25(OH)D levels below 50 nmol/L. Serum 1,25(OH)₂D was inversely correlated to bone mineral density in distal radius (p = 0.002), but not to bone mineral density at lumbar spine or femoral neck. The vitamin D receptor polymorphism Apa1 (rs7975232) was associated with bone mineral density in the lumbar spine.

Conclusions

The results suggest that PHPT patients with high blood concentrations of 1,25(OH)₂D may have the most deleterious skeletal effects. Randomized, prospective studies are necessary to elucidate whether vitamin D supplementation additionally increases serum 1,25(OH)₂D and possibly enhances the adverse effects on the skeleton in patients with PHPT.     

Nasal Levels of Antimicrobial Peptides in Allergic Asthma Patients and Healthy Controls: Differences and Effect of a Short 1,25(OH)2 Vitamin D3 Treatment

Background

Allergy is often accompanied by infections and lower levels of antimicrobial peptides (AMPs). Vitamin D has been shown to increase expression of selected AMPs. In this study we investigated whether antimicrobial peptide levels in nasal secretions of allergic asthma patients are lower than in healthy controls, and whether administration of the active form of vitamin D (1,25(OH)₂D3) affects these antimicrobial peptide levels.

Methods

The levels of antimicrobial peptides in nasal secretions were compared between 19 allergic asthma patients and 23 healthy controls. The effect of seven days daily oral treatment with 2 μg 1,25(OH)₂D3 on antimicrobial peptides in nasal secretions was assessed in a placebo-controlled cross-over clinical study.

Results

Levels of neutrophil α-defensins (human neutrophil peptides 1–3; HNP1-3) and lipocalin 2 (LCN2; also known as NGAL) were significantly lower in asthmatics, but no differences in LL-37 and SLPI were detected. Treatment with a short-term 1,25(OH)₂D3 caused a small increase in HNP1-3, but not when the asthma and control groups were analyzed separately. LL-37, LCN2 and SLPI did not change after treatment with 1,25(OH)₂D3.

Conclusion

Levels of the antimicrobial peptides HNP1-3 and LCN2 are lower in nasal secretions in asthmatics and are not substantially affected by a short-term treatment with active vitamin D.     

High Prevalence of Vitamin D Deficiency in Native versus Migrant Mothers and Newborns in the North of Italy: A Call to Act with a Stronger Prevention Program

Background

Vitamin D status during pregnancy is related to neonatal vitamin D status. Vitamin D deficiency has been associated with an increased risk of rickets in children and osteomalacia in adults. Aim of this study was to investigate 25OHD levels in maternal serum and in neonatal blood spots in native and migrant populations living in Novara (North Italy, 45°N latitude).

Methods and Findings

We carried out a cross sectional study from April 1st 2012 to March 30th 2013, in a tertiary Care Center. Maternal blood samples after delivery and newborns'' blood spots were analyzed for 25OHD levels in 533 pairs. Maternal country of origin, skin phototype, vitamin D dietary intake and supplementation during pregnancy were recorded. Multivariate regression analysis, showed a link between neonatal and maternal 25OHD levels (R-square:0.664). Severely deficient 25OHD values (<25 nmol/L) were found in 38% of Italian and in 76.2% of migrant’s newborns (p <0.0001), and in 18% of Italian and 48,4% of migrant mothers (p <0.0001) while 25OHD deficiency (≥25 and <50 nmol/L) was shown in 40.1% of Italian and 21.7% of migrant’s newborns (p <0.0001), and in 43.6% of Italian and 41.3% of migrant mothers (p <0.0001). Italian newborns and mothers had higher 25OHD levels (34.4±19.2 and 44.9±21.2nmol/L) than migrants (17.7±13.7 and 29.7±16.5nmol/L; p<0.0001). A linear decrease of 25OHD levels was found with increasing skin pigmentation (phototype I 42.1 ±18.2 vs phototype VI 17.9±10.1 nmol/l; p<0.0001). Vitamin D supplementation resulted in higher 25OHD values both in mothers and in their newborns (p<0.0001).

Conclusions

Vitamin D insufficiency in pregnancy and in newborns is frequent especially among migrants. A prevention program in Piedmont should urgently be considered and people identified as being at risk should be closely monitored. Vitamin D supplementation should be taken into account when considering a preventative health care policy.     

1,25 Dihydroxyvitamin D3 Inhibits TGFβ1-Mediated Primary Human Cardiac Myofibroblast Activation

Aims

Epidemiological and interventional studies have suggested a protective role for vitamin D in cardiovascular disease, and basic research has implicated vitamin D as a potential inhibitor of fibrosis in a number of organ systems; yet little is known regarding direct effects of vitamin D on human cardiac cells. Given the critical role of fibrotic responses in end stage cardiac disease, we examined the effect of active vitamin D treatment on fibrotic responses in primary human adult ventricular cardiac fibroblasts (HCF-av), and investigated the relationship between circulating vitamin D (25(OH)D₃) and cardiac fibrosis in human myocardial samples.

Methods and Results

Interstitial cardiac fibrosis in end stage HF was evaluated by image analysis of picrosirius red stained myocardial sections. Serum 25(OH)D₃ levels were assayed using mass spectrometry. Commercially available HCF-av were treated with transforming growth factor (TGF)β₁ to induce activation, in the presence or absence of active vitamin D (1,25(OH)₂D₃). Functional responses of fibroblasts were analyzed by in vitro collagen gel contraction assay. 1,25(OH)₂D₃ treatment significantly inhibited TGFβ₁-mediated cell contraction, and confocal imaging demonstrated reduced stress fiber formation in the presence of 1,25(OH)₂D₃. Treatment with 1,25(OH)₂D₃ reduced alpha-smooth muscle actin expression to control levels and inhibited SMAD2 phosphorylation.

Conclusions

Our results demonstrate that active vitamin D can prevent TGFβ1-mediated biochemical and functional pro-fibrotic changes in human primary cardiac fibroblasts. An inverse relationship between vitamin D status and cardiac fibrosis in end stage heart failure was observed. Collectively, our data support an inhibitory role for vitamin D in cardiac fibrosis.     

Vitamin D Metabolites and Their Association with Calcium,Phosphorus, and PTH Concentrations,Severity of Illness,and Mortality in Hospitalized Equine Neonates

Background

Hypocalcemia is a frequent abnormality that has been associated with disease severity and outcome in hospitalized foals. However, the pathogenesis of equine neonatal hypocalcemia is poorly understood. Hypovitaminosis D in critically ill people has been linked to hypocalcemia and mortality; however, information on vitamin D metabolites and their association with clinical findings and outcome in critically ill foals is lacking. The goal of this study was to determine the prevalence of vitamin D deficiency (hypovitaminosis D) and its association with serum calcium, phosphorus, and parathyroid hormone (PTH) concentrations, disease severity, and mortality in hospitalized newborn foals.

Methods and Results

One hundred newborn foals ≤72 hours old divided into hospitalized (n = 83; 59 septic, 24 sick non-septic [SNS]) and healthy (n = 17) groups were included. Blood samples were collected on admission to measure serum 25-hydroxyvitamin D₃ [25(OH)D₃], 1,25-dihydroxyvitamin D₃ [1,25(OH) ₂D₃], and PTH concentrations. Data were analyzed by nonparametric methods and univariate logistic regression. The prevalence of hypovitaminosis D [defined as 25(OH)D₃ <9.51 ng/mL] was 63% for hospitalized, 64% for septic, and 63% for SNS foals. Serum 25(OH)D₃ and 1,25(OH) ₂D₃ concentrations were significantly lower in septic and SNS compared to healthy foals (P<0.0001; P = 0.037). Septic foals had significantly lower calcium and higher phosphorus and PTH concentrations than healthy and SNS foals (P<0.05). In hospitalized and septic foals, low 1,25(OH)₂D₃ concentrations were associated with increased PTH but not with calcium or phosphorus concentrations. Septic foals with 25(OH)D₃ <9.51 ng/mL and 1,25(OH) ₂D₃ <7.09 pmol/L were more likely to die (OR=3.62; 95% CI = 1.1-12.40; OR = 5.41; 95% CI = 1.19-24.52, respectively).

Conclusions

Low 25(OH)D₃ and 1,25(OH)₂D₃ concentrations are associated with disease severity and mortality in hospitalized foals. Vitamin D deficiency may contribute to a pro-inflammatory state in equine perinatal diseases. Hypocalcemia and hyperphosphatemia together with decreased 1,25(OH)₂D₃ but increased PTH concentrations in septic foals indicates that PTH resistance may be associated with the development of these abnormalities.     

25-Hydroxyvitamin D3 Deficiency Independently Predicts Cognitive Impairment in Patients with Systemic Lupus Erythematosus

Objectives

Cognitive dysfunction has been reported in 20–80% of SLE patients. Converging evidence has indicated the importance of vitamin D as a neuroimmunomodulator for cognitive function. In this study, we evaluated the relationship between vitamin D and cognitive dysfunction.

Methods

Consecutive age- and gender-matched SLE patients and healthy controls (HCs) were administered Automated Neuropsychological Assessment Metrics in this cross-sectional study. The primary outcome was the total throughput score (TTS). Anxiety and depression were measured using the Hospital Anxiety and Depression Scale (HADS). Levels of 25-hydroxyvitamin D [25(OH)D₃ and total 25(OH)D] were measured using Liquid Chromatography-Tandem Mass Spectrometry.

Results

In total, 61 SLE patients and 61 HCs were studied. SLE patients scored significantly lower than HCs in the TTS (p = 0.004). There were no statistically significant differences in 25(OH)D₃ levels, total 25(OH)D levels and total 25(OH)D deficiency between SLE patients and HCs. However, more SLE patients had 25(OH)D₃ deficiency compared to HCs [12 (19.7%) versus 2 (3.3%), p = 0.003]. Deficiency of 25(OH)D₃ (β = -63.667, SE = 27.456, p = 0.025), but not other vitamin D variables, independently predicted worse TTS after adjusting for age, education, gender, ethnicity, HADS-Total, duration of SLE, SELENA-SLEDAI, SLICC/ACR Damage Index and cumulative steroid dose in SLE patients. Age (β = -4.261, SE = 0.866, p < 0.001) was the only predictor of TTS after adjusting for education, gender, ethnicity, HADS-Total, vitamin D levels or status in HCs.

Conclusions

Deficiency of 25(OH)D₃, a potentially modifiable risk factor, independently predicted cognitive impairment in SLE patients.     

Interactions between Serum Vitamin D Levels and Vitamin D Receptor Gene FokI Polymorphisms for Renal Function in Patients with Type 2 Diabetes

Background

We aimed to examine associations among serum 25-hydroxyvitamin D (25OHD) levels, 1,25-dihyroxyvitamin D (1,25OHD) levels, vitamin D receptor (VDR) polymorphisms, and renal function based on estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes.

Methods

In a cross-sectional study of 410 patients, chronic kidney disease (CKD) stage assessed by eGFR was compared with 25OHD, 1,25OHD, and VDR FokI (rs10735810) polymorphisms by an ordered logistic regression model adjusted for the following confounders: disease duration, calendar month, use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers or statins, and serum calcium, phosphate, and intact parathyroid hormone levels.

Results

1,25OHD levels, rather than 25OHD levels, showed seasonal oscillations; peak levels were seen from May to October and the lowest levels were seen from December to February. These findings were evident in patients with CKD stage 3∼5 but not stage 1∼2. eGFR was in direct proportion to both 25OHD and 1,25OHD levels (P<0.0001), but it had stronger linearity with 1,25OHD (r = 0.73) than 25OHD (r = 0.22) levels. Using multivariate analysis, 1,25OHD levels (P<0.001), but not 25OHD levels, were negatively associated with CKD stage. Although FokI polymorphisms by themselves showed no significant associations with CKD stage, a significant interaction between 1,25OHD and FokITT was observed (P = 0.008). The positive association between 1,25OHD and eGFR was steeper in FokICT and CC polymorphisms (r = 0.74) than FokITT polymorphisms (r = 0.65).

Conclusions

These results suggest that higher 1,25OHD levels may be associated with better CKD stages in patients with type 2 diabetes and that this association was modified by FokI polymorphisms.     

Vitamin D,Vitamin D Binding Protein,and Longitudinal Outcomes in COPD

Background

Associations between Vitamin D₃ [25(OH)D], vitamin D binding protein (VDBP) and chronic obstructive pulmonary disease (COPD) are previously reported. We aimed to further investigate these associations on longitudinal outcomes.

Methods

426 COPD patients from western Norway, GOLD stage II-IV, aged 40–76, were followed every six-month from 2006 through 2009 with spirometry, bioelectrical impedance measurements and registration of exacerbation frequency. Serum 25(OH)D and VDBP levels were determined at study-entry by high-performance liquid chromatography coupled with mass spectrometry and enzyme immunoassays respectively. Yearly change in lung function and body composition was assessed by generalized estimating equations (GEE), yearly exacerbation rate by negative binomial regression models, and 5 years all-cause mortality by Cox proportional-hazard regression.

Results

1/3 of the patients had vitamin D deficiency (<20ng/mL) and a greater decline in both FEV1 and FVC, compared to patients with normal levels; for FEV1 this difference only reached statistical significance in the 28 patients with the lowest levels (<10ng/mL, p = 0.01). Neither 25(OH)D nor VDBP levels predicted exacerbation rate, change in fat free mass index or risk of death.

Conclusion

Severe vitamin D deficiency may affect decline in lung function parameters in COPD. Neither 25(OH)D nor VDBP levels did otherwise predict markers of disease progression.     

Maternal Vitamin D Status in Preeclampsia: Seasonal Changes Are Not Influenced by Placental Gene Expression of Vitamin D Metabolizing Enzymes

Preeclampsia, a hypertensive disorder in pregnancy develops in 2–8% of pregnancies worldwide. Winter season and vitamin D deficiency have been associated with its onset.

Objective

To investigate the influence of season on maternal vitamin D status and placental vitamin D metabolism.

Methods

25-OH vitamin D and 1,25-(OH)₂ vitamin D were measured in maternal serum obtained during the winter or summer months from 63 pregnant women at delivery (43 healthy, 20 preeclampsia). In a subgroup, mRNA expression of CYP24A1 (24-hydroxylase), CYP27B1 (1α-hydroxylase) and VDR (vitamin D receptor) were quantified by real time PCR in placental samples of 14 women with normal pregnancies and 13 with preeclampsia.

Results

In patients with preeclampsia,25-OH vitamin D levels were lower, but differed significantly from controls only in summer (18.21±17.1 vs 49.2±29.2 ng/mL, P<0.001), whereas 1,25-(OH)₂ vitamin D levels were significantly lower only in winter (291±217 vs 612.3±455 pmol/mL, P<0.05). A two-factorial analysis of variance produced a statistically significant model (P<0.0001) with an effect of season (P<0.01) and preeclampsia (P = 0.01) on maternal 25-OH vitamin D levels, as well as a significant interaction between the two variables (P = 0.02). Placental gene expression of CYP24A1, CYP27B1, and VDR did not differ between groups or seasons. A negative correlation between placental gene expression of CYP24A1 and CYP27B1 was observed only in healthy controls (r = −0.81, P<0.0001).

Summary

Patients with preeclampsia displayed lower vitamin D serum levels in response to seasonal changes.The regulation of placental CYP24A1, but not of the VDR or CYP27B1 might be altered in preeclampsia.     

Effects of High Doses of Cholecalciferol in Normal Subjects: A Randomized Double-Blinded,Placebo-Controlled Trial

Background

Vitamin D repletion with high doses of vitamin D is often recommended to patients and healthy subjects. The safety, especially concerning changes in urinary calcium excretion is of great importance.

Methods

In a double-blinded, placebo-controlled study in 40 healthy volunteers, we examined the changes in mineral metabolism during supplementation with 3000 IU of oral cholecalciferol daily during 4 months.

Results

Both 25(OH)vitamin D and 1,25(OH)₂vitamin D increased significantly in the active treated group as compared to the placebo group (186% versus 14% (P<0.001) and 28% versus – 8% (P<0.001)). No change was observed in urinary calcium excretion in the active group compared to the placebo group (P = 0.891). Fibroblast growth factor 23 increased significantly by 10% (P<0.018) in the active group. However, there was no difference in changes in FGF23 between treatment groups (P = 0.457).

Conclusion

High dose cholecalciferol significantly increases 25(OH)vitamin D and 1,25(OH)₂vitamin D levels compared to placebo. No changes in urinary calcium excretion or other measured components of the mineral metabolism were found between groups.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00952562","term_id":"NCT00952562"}}NCT00952562.     

Vitamin D Deficiency in Unselected Patients from Swiss Primary Care: A Cross-Sectional Study in Two Seasons

Background

As published data on 25-hydroxy-cholecalciferol (25(OH)D) deficiency in primary care settings is scarce, we assessed the prevalence of hypovitaminosis D, potential associations with clinical symptoms, body mass index, age, Vitamin D intake, and skin type in unselected patients from primary care, and the extent of seasonal variations of serum 25(OH)D concentrations.

Methodology/Principal Findings

25(OH)D was measured at the end of summer and/or winter in 1682 consecutive patients from primary care using an enzyme-linked immunosorbant assay. Clinical symptoms were assessed by self-report (visual analogue scale 0 to 10), and vitamin D deficiency was defined as 25(OH)D concentrations < 50 nmol/l. 25(OH)D deficiency was present in 995 (59.2%) patients. 25(OH)D deficient patients reported more intense muscle weakness (visual analogue scale 2.7, 95% confidence interval 2.5 to 2.9) and had a higher body mass index (25.9kg/m², 25.5 to 26.2) than non-deficient patients (2.5, 2.3 to 2.7; and 24.2, 23.9 to 24.5, respectively). 25(OH)D concentrations also weakly correlated with muscle weakness (Spearman’s rho -0.059, 95% confidence interval -0.107 to -0.011) and body mass index (-0.156, -0.202 to -0.108). Self-reported musculoskeletal pain, fatigue, and age were not associated with deficiency, nor with concentrations. Mean 25(OH)D concentrations in patients with vitamin D containing medication were higher (60.6 ± 22.2 nmol/l) than in patients without medication (44.8 ± 19.2 nmol/l, p < 0.0001) but still below the targeted level of 75 nmol/l. Summer and winter 25(OH)D concentrations differed (53.4 ± 19.9 vs. 41.6 ± 19.3nmol/l, p < 0.0001), which was confirmed in a subgroup of 93 patients who were tested in both seasons (p = 0.01).

Conclusion/Significance

Nearly 60% of unselected patients from primary care met the criteria for 25(OH)D deficiency. Self-reported muscle weakness and high body mass index were associated with lower 25(OH)D levels. As expected 25(OH)D concentrations were lower in winter compared to summer.     

The Association between Pre-Treatment Serum 25-Hydroxyvitamin D and Survival in Newly Diagnosed Stage IV Prostate Cancer

Background/Aims

Emerging evidence in the literature suggests a positive association between serum 25-hydroxyvitamin D [25(OH)D], a standard indicator of vitamin D status, and survival in certain types of cancer. We investigated this relationship in newly diagnosed stage IV prostate cancer patients.

Methods

A consecutive cohort of 125 newly diagnosed stage IV prostate cancer patients underwent a baseline serum 25(OH)D evaluation prior to receiving any treatment at our institution between January 2008 and December 2011. We used the vitamin D categories of “deficient (<20 ng/ml)”, “insufficient (20 to 32 ng/ml)”, and “sufficient (>32 ng/ml)”. Cox regression was used to evaluate the prognostic significance of serum 25(OH)D after adjusting for relevant confounders.

Results

Mean age at diagnosis was 60 years. Of the 125 patients, 32 (25.6%) were deficient, 49 (39.2%) were insufficient and 44 (35.2%) were sufficient in vitamin D at the time of diagnosis. The median survival in deficient, insufficient and sufficient cohorts was 47.8, 44.0 and 52.6 months respectively (p = 0.60). On univariate analysis, four variables demonstrated a statistically significant association with survival: nutritional status, bone metastasis, corrected serum calcium and serum albumin (p<0.05 for all). On multivariate analysis, five variables demonstrated statistically significant associations with survival: hospital location, age, bone metastasis, serum albumin and corrected serum calcium (p<0.05 for all). Serum vitamin D status was not significant on either univariate or multivariate analysis.

Conclusion

Contrary to previously published research, we found no significant association between pre-treatment serum 25(OH)D and survival in newly diagnosed stage IV prostate cancer patients. The lack of a significant association between serum vitamin D and survival in our study could perhaps be due to the fact that the disease was far too advanced in our patients for vitamin D levels to have any impact on prognosis.     

Risk Factors for Vitamin D Deficiency among Veterans with and without HIV Infection

Objectives

We aimed to describe and compare the prevalence of vitamin D deficiency between HIV-negative and HIV-infected veterans in the southern United States, and to determine risk factors for vitamin D deficiency for HIV infected patients.

Methods

Cross-sectional, retrospective study including all patients followed at the Atlanta VA Medical Center with the first 25-hydroxyvitamin D [25(OH)D] level determined between January 2007 and August 2010. Multivariate logistic regression analysis was used to determine risk factors associated with vitamin D deficiency (< 20 ng/ml).

Results

There was higher prevalence of 25(OH)D deficiency among HIV-positive compared to HIV-negative patients (53.2 vs. 38.5%, p <0.001). Independent risk factors for vitamin D deficiency in HIV + patients included black race (OR 3.24, 95% CI 2.28–4.60), winter season (OR 1.39, 95% CI 1.05–1.84) and higher GFR (OR 1.01, CI 1.00–1.01); increasing age (OR 0.98, 95% CI 0.95–0.98), and tenofovir use (OR 0.72, 95% CI 0.54–0.96) were associated with less vitamin D deficiency.

Conclusions

Vitamin D deficiency is a prevalent problem that varies inversely with age and affects HIV-infected patients more than other veterans in care. In addition to age, tenofovir and kidney disease seem to confer a protective effect from vitamin D deficiency in HIV-positive patients.     

Vitamin D Status and the Risk for Hospital-Acquired Infections in Critically Ill Adults: A Prospective Cohort Study

Introduction

To identify patient characteristics associated with low serum 25-hydroxyvitamin D (25(OH)D) concentrations in the medical intensive care unit (ICU) and examine the relationship between serum 25(OH)D and the risk for hospital-acquired infections.

Methods

This is a prospective observational cohort of adult patients admitted to the medical ICU at an urban safety net teaching hospital in Atlanta, Georgia from November 1, 2011 through October 31, 2012 with an anticipated ICU stay ≥ 1 day. Phlebotomy for serum 25(OH)D measurement was performed on all patients within 5 days of ICU admission. Patients were followed for 30 days or until death or hospital discharge, whichever came first. Hospital-acquired infections were determined using standardized criteria from review of electronic medical record.

Results

Among the 314 patients analyzed, 178 (57%) had a low vitamin D at a serum 25(OH)D concentration < 15 ng/mL. The patient characteristics associated with low vitamin D included admission during winter months (28% vs. 18%, P = 0.04), higher PaO2/FiO2 (275 vs. 226 torr, P = 0.03) and a longer time from ICU admission to study phlebotomy (1.8 vs. 1.5 days, P = 0.02). A total of 36 (11%) patients were adjudicated as having a hospital-acquired infection and in multivariable analysis adjusting for gender, alcohol use, APACHE II score, time to study phlebotomy, ICU length of stay and net fluid balance, serum 25(OH)D levels < 15 ng/mL were not associated with risk for hospital-acquired infections (HR 0.85, 95% CI 0.40-1.80, P = 0.7).

Conclusions

In this prospective, observational cohort of adults admitted to a single-center medical ICU, we did not find a significant association between low 25(OH)D and the risk for hospital-acquired infections.     

Vitamin D Deficiency and Insufficiency in Hospitalized COPD Patients

Introduction

31–77% of patients with COPD have vitamin D deficiency and insufficiency, with results being highly variable between studies. Vitamin D may also correlate with disease characteristics.

Aim

To find out the prevalence of vitamin D deficiency and insufficiency in patients with COPD admitted for exacerbation and a risk factors for lower vitamin D levels among comorbidities and COPD characteristics.

Methods

152 patients were studied for vitamin D serum levels (25(OH)D). All of them were also assessed for diabetes mellitus (DM) and metabolic syndrome (MS). Data were gathered also for smoking status and exacerbations in last year. All patients completed CAT and mMRC questionnaires and underwent spirometry.

Results

A total of 83,6% of patients have reduced levels of vitamin D. 42,8% (65/152) have vitamin D insufficiency (defined as 25–50 nmol/L) and 40,8% (62/152) have vitamin D deficiency (<25 nmol/L). The mean level of 25(OH)D for all patients is 31,97 nmol/L (95%CI 29,12–34,68). Vitamin D deficiency and insufficiency are more prevalent in females vs. males (97,7 vs 77,8%; p = 0.003). The prevalence and severity of vitamin D deficiency and insufficiency in this study is significantly higher when compared to an unselected Bulgarian population (prevalence 75,8%; mean level 38,75 nmol/L). Vitamin D levels correlate with quality of life (measured by the mMRC scale) and lung function (FVC, FEV1, FEV6, FEF2575, FEV3, but not with FEV1/FVC ratio and PEF), it does not correlate with the presence of arterial hypertension, DM, MS and number of moderate, severe and total exacerbations. Vitamin D deficiency is a risk factor for longer hospital stay.

Conclusions

The patients with COPD admitted for exacerbation are a risk group for vitamin D deficiency and insufficiency, which is associated with worse disease characteristics.     

Cardio-Metabolic Disease Risks and Their Associations with Circulating 25-Hydroxyvitamin D and Omega-3 Levels in South Asian and White Canadians

Objectives

This study compared cardio-metabolic disease risk factors and their associations with serum vitamin D and omega-3 status in South Asian (SAC) and White Canadians (WC) living in Canada’s capital region.

Methods

Fasting blood samples were taken from 235 SAC and 279 WC aged 20 to 79 years in Ottawa, and 22 risk factors were measured.

Results

SAC men and women had significantly higher fasting glucose, insulin, homeostasis model assessment for insulin resistance (HOMA-IR), apolipoprotein B (ApoB), ratios of total (TC) to HDL cholesterol (HDLC) and ApoB to ApoA1, leptin, E-selectin, P-selectin, ICAM-1 and omega-3 (p < 0.05), but lower HDLC, ApoA1, vitamin D levels than WC (p < 0.05). SAC women had higher CRP and VEGF than WC women. Adequate (50–74.9 nmol/L) or optimal (≥ 75 nmol/L) levels of 25(OH)D were associated with lower BMI, glucose, insulin, HOMA-IR, TG, TC, low density lipoprotein cholesterol (LDLC), ApoB/ApoA1 ratio, CRP, leptin, and higher HDLC, ApoA1, omega-3 index, L-selectin levels in WC, but not in SAC. Intermediate (>4%-<8%) or high (≥ 8%) levels of omega-3 indices were related to lower E-selectin, P-selectin, ICAM-1 and higher HDLC, 25(OH)D levels in WC, but not in SAC. The BMIs of ≤ 25 kg/m² were related to lower LDLC, ApoB, VEGF, creatinine and higher 25(OH)D in WC, but not in SAC.

Conclusions

The associations of vitamin D, omega-3 status, BMI and risk factors were more profound in the WC than SAC. Compared to WC, vitamin D status and omega-3 index may not be good predictive risk factors for the prevalence of CVD and diabetes in SAC.     

Low 25-Hydroxyvitamin D Levels Are Associated with Infections and Mortality in Patients with Cirrhosis

Background & Aims

Vitamin D, best known to regulate bone mineralization, has numerous additional roles including regulation inflammatory pathways. Recently, an increased incidence of 25-hydroxyvitamin D3 (25(OH)D₃) deficiency has been found in subjects suffering from liver diseases. We here investigated if low vitamin D levels might be associated with prognosis, inflammation and infectious complications in patients with cirrhosis.

Methods

We performed a prospective cohort study investigating the relation between 25(OH)D₃ levels and stages of cirrhosis, mortality and complications of cirrhosis, including infections.

Results

251 patients with cirrhosis were enrolled into the present prospective cohort study. 25(OH)D₃ levels were quantified by radioimmunoassay from serum samples obtained at study inclusion. The mean follow-up time was 411 ± 397 days with a range of 1-1382 days. 30 (12.0%) patients underwent liver transplantation and 85 (33.8%) individuals died within the study. The mean serum 25(OH)D₃ concentration was 8.93 ± 7.1 ng/ml with a range of 1.0 to 46.0 ng/ml. 25(OH)D₃ levels differed significantly between Child Pugh scores and showed a negative correlation with the model of end stage liver disease (MELD) score. Patients with decompensated cirrhosis and infectious complications, had significantly lower 25(OH)D₃ levels compared to subjects without complications. Low 25(OH)D₃ was associated with mortality in uni- as well as multivariate Cox regression models.

Conclusions

25(OH)D₃ deficiency is associated with advanced liver disease and low 25(OH)D₃ levels are an indicator for a poor outcome and are associated with infectious complications.