Vitamin D supplementation in a post-pandemic era: A narrative review.

Vitamin D is a fat-soluble molecule referring to the different isoforms, ergocalciferol (D2) and cholecalciferol (D3). Its physiological functions include increasing calcium serum concentrations. 25-hydroxyvitamin D3 (25(OH)D) (Calcifediol), a non-active, circulating instant precursor is seen as a pre-hormone. Studies have shown that a deficiency in calcifediol is related to chronic conditions such as cardiovascular, musculoskeletal, immune system, neurological, and anti-neoplastic functions. Vitamin D supplementation has shown its benefit as prophylaxis and treatment during the coronavirus disease 2019 (COVID-19) pandemic and an increase in the prescribing of vitamin D supplementation has been observed. The intention of this review article is to provide guidance on the recommended dosage regimen as a prophylactic measure during COVID-19 and its use as a supplement in general. From this review article, it is clear that vitamin D has an important role to play not only in COVID-19 but also in various other health aspects of the human body.Contribution: This review article highlighted the role of vitamin D in managing vitamin D deficiency and its role as a supplement in the management of respiratory tract infections, especially COVID-19. This overview can assist physicians in optimising healthcare by optimised dosing recommendations and indications.

Effect of Vitamin D Supplementation on (25(OH)D) Status in Children 12-30 Months of Age: A Randomized Clinical Trial.

Vitamin D (VD) deficiency (serum 25(OH)D < 50 nmol/L) affects 27.3% of preschool children in Mexico. The purpose of this study was to assess the effect of vitamin D supplementation at different doses on serum 25(OH)D concentrations in preschool children. In a randomized control trial, 222 children 12-30 months old were randomly assigned to one of four treatment groups: (1) Vitamin D2 (Ergocalciferol) 400 IU/day (n = 56); (2) Vitamin D2 (Ergocalciferol) 800 IU/day (n = 55); (3) Vitamin D3 (Cholecalciferol) 1000 IU/day (n = 56); or (4) multiple micronutrients (MM) non-VD (n = 55). Supplements were given five days/wk for three months. Serum 25(OH)D was measured at baseline and after three months. At baseline, mean serum 25(OH)D was 58.9 ± 12.6 nmol/L and 23.4% were VD-deficient. There was a statistically significant increase in serum concentrations of 25(OH)D (range across groups: +8.2 to +17.3 nmol/L). Additionally, the prevalence of vitamin D deficiency decreased after three months: for D2 400 IU, -9.0%; for D2 800 IU, -11.0%; for D3 1000 IU, -18.0%; and for MM non-VD, -2.8% (p < 0.05). No adverse effects were observed. VD supplementation for three months was effective for increasing serum 25(OH)D concentrations and for reducing VD deficiency in preschool children. The highest efficacy was observed by giving 1000 IU D3/d.

Determination of Optimal Vitamin D Dosage in Children with Cholestasis.

BACKGROUND: Vitamin D deficiency in patients with cholestasis is due to impaired intestinal vitamin D absorption, which results from decreased intestinal bile acid concentration. Patients with cholestasis usually do not achieve optimal vitamin D status when a treatment regimen for children without cholestasis is used. However, data on high-dose vitamin D treatment in patients with cholestasis are limited. METHODS: This study is a prospective study that included pediatric patients with cholestasis (serum direct bilirubin > 1 mg/dL) who had vitamin D deficiency (serum 25-hydroxyvitamin D, 25-OHD, < 20 ng/mL). In Phase 1, single-day oral loading of 300,000 IU (or 600,000 IU if weight ≥ 20 kg) of vitamin D2 was administered, followed by an additional loading if serum 25-OHD < 30 ng/mL, and 4-week continuation of treatment using a vitamin D2 dose calculated based on the increment of 25-OHD after first loading. In Phase 2, oral vitamin D2 (200,000 IU/day) was administered for 12 days, followed by 400,000 IU/day of vitamin D2 orally for another 8 weeks if serum 25-OHD < 30 ng/mL. RESULTS: Phase 1: Seven patients were enrolled. Three out of seven patients had a moderate increase in serum 25-OHD after loading (up to 20.3-27.2 ng/mL). These patients had conditions with partially preserved bile flow. The remaining four patients, who had biliary atresia with failed or no Kasai operation, had low increments of serum 25-OHD. Phase 2: Eleven patients were enrolled. Eight out of 11 patients had a moderate increase in serum 25-OHD after 200,000 IU/day of vitamin D2 for 12 days. Serum 25-OHD continued increasing after administering 400,000 IU/day of vitamin D2 for another 8 weeks, with maximal serum 25-OHD of 15.7-22.8 ng/mL. CONCLUSION: Very high doses of vitamin D2 (200,000 and 400,000 IU/day) partly overcame poor intestinal vitamin D absorption and resulted in moderate increases in serum 25-OHD in pediatric patients with cholestasis, particularly when cholestasis was caused by uncorrectable bile duct obstruction.

Vitamin D in hypoparathyroidism: insight into pathophysiology and perspectives in clinical practice.

Hypoparathyroidism (HypoPT) is a rare endocrine disorder characterized by the absence or insufficient parathyroid hormone production resulting in chronic hypocalcemia. Complications of HypoPT include perturbation of several target organs. The conventional treatment consists of the administration of active vitamin D, namely calcitriol. Regarding vitamin D status, few data are available, mostly in HypoPT subjects supplemented with parent vitamin D. In addition, perturbation of vitamin D metabolism has been poorly investigated, as well as the contribution of altered vitamin D status on the clinical expression of the disease. The most recent consensus on the management of chronic HypoPT suggests the baseline evaluation of serum 25-hydroxy-vitamin D [25(OH)D] and supplementation with parent vitamin D with the aim to achieve and maintain serum 25(OH)D levels in the range of 30-50 ng/mL. The rationale for using supplementation with parent vitamin D (either ergocalciferol or cholecalciferol) in HypoPT would be to provide sufficient 25(OH)D substrate to the residual 1-α-hydroxylase activity, thus ensuring its conversion to active vitamin D in renal and extra-renal tissues. More data from experimental and clinical studies are needed for better assessing how these mechanisms may significantly influence metabolic control in HypoPT and eventually skeletal and extra-skeletal manifestation of the disease. Finally, future data will clarify how the currently available parent vitamin D compounds (ergocalciferol, cholecalciferol, calcifediol) would perform in addressing these specific issues.

Vitamin D Supplementation Has No Impact on Cardiorespiratory Fitness, but Improves Inflammatory Status in Vitamin D Deficient Young Men Engaged in Resistance Training.

Data on the effect of vitamin D (Vit-D) supplementation on cardiorespiratory fitness (VO2max) are conflicting. A possible source of discrepancies in the literature is the heterogeneity in baseline Vit-D status among participants in previous studies. The main objectives of the present study were to assess the impact of Vit-D supplementation on VO2max and inflammatory status in Vit-D deficient young healthy men. Participants (n = 39, baseline serum Vit-D level < 50 nmol/L) were quasi-randomly assigned to one of the two groups, which, in a double-blind manner, supplemented their diet daily with either Vit-D (8000 IU; VD) or placebo (PLC) and concomitantly performed a 12-week supervised resistance training program. During the 12-week intervention, serum Vit-D concentrations increased 3.9-fold (p < 0.001) in the VD group while no changes occurred in the PLC group. Baseline VO2max did not differ in the two groups and remained unchanged during the intervention. Serum interleukin-10/tumour necrosis factor alpha ratio increased significantly (30%, p = 0.007; effect size 0.399) in VD but not in PLC group. In conclusion, 12-week Vit-D supplementation increases serum 25(OH)D levels and improves inflammatory status, but has no impact on VO2max in Vit-D deficient young men engaged in resistance training.

Standard and high dose ergocalciferol regimens for treatment of hypovitaminosis D in epileptic children and adolescents.

OBJECTIVES: Children with epilepsy are at increased risk of vitamin D deficiency. We aimed to compare the effect of two ergocalciferol regimens given for 90 days. METHODS: Epileptic patients aged 5-18 years who received at least one antiepileptic drug (AED) for more than 6 months and had serum 25-OHD <30 ng/mL were randomized to receive 20,000 IU/10 d (standard dose, n=41) or 60,000 IU/10 d (high dose, n=41) of oral ergocalciferol. Serum Ca, P, Mg, ALP, iPTH and urine Ca/Cr ratio were measured at baseline and after 90 days of treatment. Change in serum 25-OHD and vitamin D status after treatment was evaluated. RESULTS: The initial serum 25-OHD in the standard dose and high dose group was 19.5 ± 4.9 and 18.4 ± 4.6 ng/mL, respectively. Serum 25-OHD after treatment was significantly higher in the high dose group (39.0 ± 11.5 vs. 27.5 ± 8.6 ng/mL, p<0.05). The average increase in serum 25-OHD in the high dose and standard dose group was 20.6 ± 11.4 and 7.2 ± 7.5 ng/mL, respectively (p<0.05). Normalized serum 25-OHD was achieved in 80.5% of the high dose group compared to 36.6% of the standard dose group (p<0.05). No adverse events were found. Patients with a BMI Z-score>0 had a 2.5 times greater risk of continued hypovitaminosis D after treatment compared to those with a BMI Z-score<0 (95% CI: 1.0-5.9, p<0.05). CONCLUSIONS: Oral ergocalciferol 60,000 IU/10 d for 90 days was more effective at normalizing serum 25-OHD than 20,000 IU/10 d in epileptic children and adolescents who were receiving AEDs.

Extended-Release Calcifediol Effectively Raises Serum Total 25-Hydroxyvitamin D Even in Overweight Nondialysis Chronic Kidney Disease Patients with Secondary Hyperparathyroidism.

INTRODUCTION: Obesity increases the risk of vitamin D insufficiency, which exacerbates secondary hyperparathyroidism in chronic kidney disease. Recent studies suggest that serum total 25-hydroxyvitamin D (25OHD) levels of ≥50 ng/mL are necessary to produce significant reductions in elevated parathyroid hormone levels in nondialysis patients. Data from real-world and randomized controlled trials (RCTs) involving these patients were examined for (1) relationships between vitamin D treatments and the achieved levels of serum 25OHD and between serum 25OHD and body weight (BW)/body mass index (BMI); and (2) the impact of BW/BMI on achieving serum 25OHD levels ≥50 ng/mL with extended-release calcifediol (ERC) treatment or vitamin D supplementation (cholecalciferol or ergocalciferol). METHODS: Data obtained from nondialysis patients participating in two real-world studies, one conducted in Europe (Study 1) and the other (Study 2) in the USA, and in two US RCTs (Studies 3 and 4) were analyzed for serum 25OHD outcomes after treatment with ERC, vitamin D supplements, or placebo. RESULTS: More than 50% of subjects treated with vitamin D supplements in both real-world studies (Studies 1 and 2) failed to achieve serum 25OHD levels ≥30 ng/mL, a level widely viewed by nephrologists as the threshold of adequacy; only 7.3-7.5% of subjects achieved levels ≥50 ng/mL. Data from the European study (Study 1) showed that serum 25OHD levels had significant and nearly identical inverse relationships with BW and BMI, indicating that high BW or BMI thwarts the ability of vitamin D supplements to raise serum 25OHD. One RCT (Study 3) showed that 8 weeks of ERC treatment (60 µg/day) raised serum 25OHD levels to ≥30 and 50 ng/mL in all subjects, regardless of BW, while cholecalciferol (300,000 IU/month) raised serum 25OHD to these thresholds in 56% and 0% of subjects, respectively. The other RCT (Study 4) showed that ERC treatment (30 or 60 µg/day) successfully raised mean serum 25OHD levels to at least 50 ng/mL for subjects in all BW categories, whereas no increases were observed with placebo treatment. CONCLUSION: Real-world studies conducted in Europe and USA in nondialysis patients (Studies 1 and 2) showed that vitamin D supplements (cholecalciferol or ergocalciferol) were unreliable in raising serum total 25OHD to targets of 30 or 50 ng/mL. In contrast, ERC was demonstrated to be effective in one real-world study (Study 2) and two RCTs (Studies 3 and 4) conducted in US nondialysis patients in raising serum 25OHD to these targeted levels irrespective of BW.

A systematic review of the pharmacotherapy of secondary hyperparathyroidism (SHPT) in grades 3-5 Chronic Kidney Disease (CKD).

OBJECTIVE: The data on the treatment of secondary hyperparathyroidism (SHPT) provided in scientific publications are divergent and contradictory. Therefore, the aim of our systematic review was to evaluate the efficacy of SHPT treatment in (chronic kidney disease) CKD. MATERIALS AND METHODS: The Cochrane, PubMed, and Scopus databases were searched independently by two authors. The search strategy included controlled vocabulary and keywords. The effectiveness and side effects of calcifediol, ergocaliferol, calcitriol, paricalcitol, and cinacalcet were compared and analyzed. RESULTS: Extended-release (ER) calcifediol raised the total serum 25-hydroxyvitamin D level over the threshold of 30 ng/mL in 80% of the patients analyzed in the study. It is the level required for intact PTH (iPTH) suppression. ER calcifediol reduced the iPTH level by 30% in about 30% of the patients, whereas only 2.1% of them had hypercalcemia. Calcitriol significantly decreased the iPTH values. It was the cause of hypercalcemia in 1.7% of the patients. The reduction of the iPTH level by more than 30% was observed in 85.7% of the patients in the paracalcitol group after 48-week supplementation. Paricalcitol was the cause of hypercalcemia in 1.9% of the patients. The cinacalcet therapy resulted in the highest percentage of patients with the iPTH level within the limits recommended by the KDOQI (70-110 ng/L for stage 4 CKD and 150-300 ng/L for stage 5 CKD). 92% of the patients met the KDOQI guidelines and the mean decrease in the serum iPTH level was 68%. CONCLUSIONS: Calcifediol ER, paricalcitol, and cinacalcet significantly decreased the iPTH level in the patients under study. Paricalcitol increased the serum calcium concentration the most of all the drugs under analysis. It is noteworthy that only cinacalcet does not carry the risk of hypercalcemia.

Improving vitamin D status in bariatric surgery subjects with monthly high-dose ergocalciferol.

Background: Vitamin D insufficiency is common before and after bariatric surgery. Optimal supplementation to treat vitamin D insufficiency is not clearly defined. Objective: Determine if serum 25 (OH) D levels improve by the consumption of an additional monthly ergocalciferol supplement by subjects after bariatric surgery. Study design: Thirty-two subjects were randomly divided to receive an additional 100,000 IUs of ergocalciferol monthly after bariatric surgery (n=10) or standard level vitamin D supplement after bariatric surgery (n=22). Serum 25 (OH) D, calcium, and hemoglobin A1c levels were measured preoperatively and one year after bariatric surgery. Results: Mean changes in BMI at 1-year post-operation was -18.12±6.46 kg/m2 in the control group versus -18.84±4.7 kg/m2; p=0.638 in the vitamin D group. One year after bariatric surgery, the mean changes from baseline in vitamin D levels were 2.69±9.4 and 12.4±17.0 ng/mL in control and intervention groups, respectively. The treated group showed a marginally higher mean increase in Vitamin D than the control group, p=0.059. Other mean changes at 1-year post-surgery that were not significantly different include calcium -0.264±0.45 and -0.21±0.509 mg/dl in control and intervention groups, respectively and HbA1c -1.0±1.21 and -0.95±0.071% in control and intervention groups, respectively. Conclusion: This study showed 100,000 IUs ergocalciferol once a month is a safe and effective treatment for vitamin D insufficiency in most patients having bariatric surgery.

Effect of Vitamin D Supplement on Vulvovaginal Atrophy of the Menopause.

The effects of oral vitamin D supplements on vaginal health in postmenopausal women with vulvovaginal atrophy (VVA) was evaluated. A double-blinded, randomized placebo-controlled trial was conducted for 12 weeks to investigate changes on vaginal maturation index (VMI), vaginal pH, and the visual analog scale (VAS) of VVA symptoms. The vitamin D group received oral ergocalciferol, at 40,000 IU per week, while the placebo group received an identical placebo capsule. Eighty postmenopausal women were enrolled. There were no significant differences in baseline characteristics between both groups. In an intention-to-treat analysis, VMI, vaginal pH, and VAS of VVA symptoms showed no significant differences between both groups at the six and 12 weeks. However, the mean difference of VMI in the vitamin D group between baseline and at six weeks showed significant improvement (5.5 + 16.27, p <0.05). Moreover, the mean vaginal pH and VAS of VVA patients in the vitamin D group were significantly improved at both six and 12 weeks compared to baseline. The oral vitamin D supplementation for 12 weeks potentially improves vaginal health outcomes in postmenopausal women with VVA symptoms, demonstrated by the improved mean VMI, vaginal pH, and VAS at six and 12 weeks between baseline, however, no significant differences were observed from the placebo treatment.

Vitamin D: does it help Tregs in active rheumatoid arthritis patients.

Background Regulatory T cells (Tregs) play an important role in the maintenance of immunological tolerance. Tregs deficiency or suppressor functions reduction may be associated with autoimmune diseases development. Objectives To estimate the effect of vitamin D supplementation on Tregs level in the peripheral blood of active rheumatoid arthritis (RA) patients. Methods 40 active RA patients were randomly assigned into two groups. Group I received methotrexate (MTX) plus hydroxychloroquine, group II received MTX, hydroxychloroquine plus vitamin D supplementation for 3 months, and 30 healthy volunteers as control group. Peripheral blood Tregs were measured at baseline and after 3 months by Flow Cytometry. Results At baseline, Tregs percentage was significantly decreased (p<0.001) in both RA patient groups (13.52±1.95%, 13.65±2.98% respectively), compared to controls (28.44±7.37%) with no significant difference between the two patient groups (p=0.866). After 3 months, there was a significant elevation in Tregs percentage in group II compared to group I (p<0.001). Tregs elevation was associated with significant DAS-28 score reduction (p<0.001). Conclusion Vitamin D appears to have important immunomodulatory functions. Vitamin D supplementation can be combined safely with traditional DMARDs to regulate the immune system. Clinical trial registration Tanta University Protocol Record 33846, Vitamin D Effect in Rheumatoid Arthritis, http://www.clinicaltrials.gov, NCT04472481.

[Cholecalciferol supplementation improves secondary hyperparathyroidism control in hemodialysis patients].

Introduction: Vitamin D deficiency is common among hemodialysis (HD) patients and is an important component in the pathogenesis of secondary hyperparathyroidism (SHPT). We herein report our experience on the impact of cholecalciferol supplementation on PTH levels in a group of HD patients. Patients and methods: We selected 122 HD patients. The main selection criteria were 25- hydroxyvitamin D (25(OH)D) levels ≤30 ng/mL and SHPT defined as PTH levels >300 pg/mL or PTH levels between 150-300 pg/mL during therapy with cinacalcet or paricalcitol. 82 patients agreed to receive cholecalciferol at the fixed dose of 25,000 IU per week orally for 12 months, while the remaining 40 represented the control group. The main endopoints of the study were the reduction in PTH levels ≥30% compared to baseline values and the increase of 25(OH)D levels to values >30 ng/mL. Results: At follow-up PTH levels decreased in the supplemented group from 476 ±293 to 296 ± 207 pg/mL (p<0.001), 25(OH)D levels increased from 10.3 ± 5.7 to 33.5 ± 11.2 ng/mL (p<0.001), serum calcium increased from 8.6 ± 0.5 to 8.8 ± 0.6 mg/dL (p<0.05) while serum phosphorus did not change. In this group the mean doses of paricalcitol were significantly reduced, from 8.7 ± 4.0 to 6.1 ± 3.9 µg/week (p<0.001). Moreover, in this group there were a significant increase of hemoglobin levels, from 11.6 ± 1.3 to 12.2 ± 1.1 g/dL (p <0.01) and a significant reduction of erythropoietin doses (p<0.05). In the control group the 25(OH)D and PTH levels did not change, while cinacalcet doses increased from 21 ±14 to 43 ± 17 mg/d (p<0.01). Conclusions: Vitamin deficiency is very common in HD patients. Cholecalciferol treatment significantly increased serum 25(OH)D levels, significantly decreased PTH levels and paricalcitol doses, concurrently entailing a better control of anemia.

A comparative analysis of the efficacy and safety of paricalcitol versus other vitamin D receptor activators in patients undergoing hemodialysis: A systematic review and meta-analysis of 15 randomized controlled trials.

Paricalcitol, a new vitamin D receptor activator (VDRA), is reported to be more effective than other VDRAs in reducing calcium and phosphorus levels in patients undergoing hemodialysis. However, the efficacy and safety of paricalcitol remain controversial. This analysis compares paricalcitol with other VDRAs in patients undergoing hemodialysis. We searched the Cochrane Library, PubMed, EMBASE, Web of Science, and CNKI up to April 22, 2019. Standardized mean difference (SMD), risk ratio (RR) and 95% confidence interval (CI) values were estimated to compare the outcomes of the groups. Two reviewers extracted data and assessed trial quality independently. All statistical analyses were performed using the standard statistical procedures of RevMan 5.2 and Stata 12.0. Fifteen studies (N = 110,544) were included in this meta-analysis. Of these studies, 11 were randomized controlled trials (RCTs) and 4 were non-randomized studies of interventions (NRSIs). Patients receiving paricalcitol experienced better overall survival (OS) than patients receiving other VDRAs, with a pooled hazard ratio of 0.86 (95% CI 0.80-0.91; P < 0.00001). Intact parathyroid hormone (iPTH) levels were significantly reduced in the paricalcitol group compared to the group receiving other VDRAs, with a pooled SMD of -0.53 (95% CI -0.89- -0.16; P = 0.004). There was a significant increase in serum calcium levels from baseline in the paricalcitol group compared to the other VDRAs group when limiting the analysis to RCTs, with a pooled SMD of 2.14 (95% CI 0.90-3.38; P = 0.0007). Changes in serum calcium levels were significantly lower in the paricalcitol group when the analysis was limited to NRSIs, with a pooled SMD of -0.85 (95% CI -1.34--0.35; P = 0.0008). The NSRI analysis also showed a significant reduction in serum phosphorus levels in the paricalcitol group, with a pooled SMD of -0.57 (95% CI -1.00--0.13; P = 0.01). No significant differences were observed in the incidence of hypercalcemia, hyperphosphatemia, or adverse events. Generally, paricalcitol seems superior to other VDRAs in reducing mortality and iPTH levels in patients undergoing hemodialysis. However, the comparative effectiveness of paricalcitol in reducing serum calcium and phosphorus levels needs further exploration. No significant difference was found in the rate of adverse events.

Paricalcitol regulatory effect on inflammatory, fibrotic and anticalcificating parameters in renal patiente. Far beyond mineral bone disease regulation. / Efecto regulador de paricalcitol sobre parámetros inflamatorios, fibróticos y anticalcificantes en el paciente con enfermedad renal crónica. Más allá de la regulación de la enfermedad óseo-mineral.

BACKWARD: Cardiovascular events are the major cause of morbidity and mortality in patients with chronic kidney disease (CKD). Inflammation and mineral-bone disorder are pathological conditions that have been associated with an increased cardiovascular risk. OBJECTIVE: Show paricalcitol regulation overinflammatory, fibrotic and mineral disorder parameters in CKD. MATERIAL AND METHODS: Prospective Study in 46 CKD stages III-V patients without dialysis patients whith elevated parathormone in which we introduced paricalcitol. We evaluated classic and newest mineral and bone metabolism serum parameters (calcium, phosphorus, parathormone, fibroblast growth factor-23 [FGF-23], Klotho, calcidiol), inflammatory-fibrosis and anticalcifying parameters (interleukin-6 and 10, tumor necrosis factor-a [TNF- α], transforming growth factor-b [TGF-ß],bone morphogenic protein-7 [BMP-7] and fetuin-A) for four months. RESULTS: At the end of study soluble Klotho increased (p=.001), FGF-23 remained stable, calcium and phosphorus levels were not increased, calcidiol increased (p=.010) and PTH decreased (p=.002). Inflammation-fibrosis and calcification parameters showed positive regulation after paricalcitol treatment: interleukin-6 decreased significantly (p=.001) and also TNF-α did (p=.005), on the contrary, interleukin-10 and fetuin-A increased (p=.001 for both). Anti-fibrosis marker BMP-7 increased (p=.001) and TGF-b decreased (p=.001). We did not find significant changes in renal function. CONCLUSIONS: Paricalcitol treatment might be profitable in regulating inflammatory and anticalcificant parameters, unmodified calcium or phosphorus seric levels and preserving kidney function in renal patients with no dialysis. Our selected parameters could indicate paricalcitol effects in mineral and endothelial disorder related to renal disease.

Impact of insufficient admission vitamin D serum concentrations on sepsis incidence and clinical outcomes in patients with thermal injury.

INTRODUCTION: In burn patients, vitamin D has been studied primarily in the pediatric population and focused mainly on the correlation with bone marker measurements and incidence of fractures. There is an association between vitamin D deficiency and the development of sepsis in non-burn critically-ill patients. However, there is limited data on vitamin D concentrations and clinical outcomes in burn patients, such as sepsis. The objective of this study is to evaluate the impact of vitamin D concentrations on the incidence of sepsis in adult burn patients. METHODS: This was a retrospective cohort of patients 18 years of age and older admitted between February 1, 2016 and February 28, 2018 to an American Burn Association (ABA) verified burn center with diagnosis of burn injury. The primary endpoint was incidence of sepsis using the ABA 2007 Sepsis Consensus Criteria between patients with adequate vitamin D concentrations (25[OH]D > 20 ng/mL) and insufficient vitamin D (25[OH]D < 20 ng/mL) concentrations measured on admission. Descriptive statistics were used for baseline demographics. Univariate analysis was conducted using Chi-square, Fisher's exact test or Mann-Whitney U test, as appropriate. RESULTS: A total of 115 patients were screened and 107 patients were included in this study. Sixty three patients (58.9%) had insufficient vitamin D concentrations. Patient demographics were overall similar between groups. The median total body surface area burned was 14.6% in the insufficient vitamin D group, and 12.1% in the adequate vitamin D group (p = 0.2). There was a trend towards greater incidence of sepsis in the insufficient vitamin D group in the univariate analysis (15.9% vs. 4.5%, p = 0.07). The multivariable logistic regression analysis found that adequate vitamin D concentrations was associated with a reduction in the incidence of sepsis (OR 0.10, 95% CI 0.01-0.88). The insufficient vitamin D group had a longer median hospital LOS (19 [IQR 11-37] vs 11.5 [IQR 7-20] days, p < 0.05), longer intensive care unit LOS (17 [IQR 10-37] vs 5 [IQR 2-19.5] days, p < 0.05) and fewer ventilator free days (26 [IQR 18-28] vs 28 [IQR 27-28] days, p < 0.05). There was no difference in mortality between groups (p = 0.69). CONCLUSIONS: Patients with adequate vitamin D concentrations on admission had a reduction in the incidence of sepsis as compared to patients with insufficient vitamin D concentrations. Insufficient vitamin D concentrations may contribute to other worsened clinical outcomes in burn patients. Our findings set the stage for future, multicenter studies to determine the role of vitamin D supplementation in burn patients.

Ergocalciferol Versus Cholecalciferol in Non-Dialysis Dependent Chronic Kidney Disease Patients: A Small Retrospective Cohort Study.

PURPOSE: The purpose of this retrospective cohort study was to measure the difference between cholecalciferol and ergocalciferol in their ability to effect vitamin D, parathyroid hormone (PTH), calcium, and phosphorous serum concentrations in patients with stage 3 or 4 chronic kidney disease. METHODS: This was a retrospective cohort study conducted within a single-center ambulatory nephrology clinic. Patients eligible for the study were identified through medical records displaying each patient's initiation on either ergocalciferol or cholecalciferol from 2013 to 2016. Patients' baseline vitamin D, PTH, calcium, and phosphorous serum concentrations were taken prior to treatment initiation, and patients were reassessed with a second measurement within 12 months of therapy. RESULTS: Out of 149 eligible patients, 110 were excluded. There were 33 patients included on cholecalciferol and 6 patients on ergocalciferol. A significant difference was observed in the percent change of phosphorous serum concentrations from baseline following drug administration (p=0.03). The mean changes from baseline to final serum phosphorous concentrations (mg/dL) were 0.12 and -0.3 for cholecalciferol and ergocalciferol, respectively. There was no significant difference in vitamin D (14.9, 15.1, p=0.97), PTH (5.6, 2.3, p=0.72), or calcium (0.05, -0.17, p=0.08) serum concentrations between cholecalciferol and ergocalciferol, respectively. There was a statistically significant increase in the mean change in serum phosphorous concentrations within the cholecalciferol group compared to the ergocalciferol group. CONCLUSION: In this small pilot study, cholecalciferol treatment appeared to increase serum phosphorous concentrations compared to ergocalciferol. These observations may warrant further large-scale studies that are appropriately powered to validate such findings.

Antifibrotic effects of hypocalcemic vitamin D analogs in murine and human hepatic stellate cells and in the CCl4 mouse model.

Liver cirrhosis is a life-threatening consequence of liver fibrosis. The aim of this study was to investigate the antifibrotic potential of clinically available vitamin D analogs compared to that of calcitriol in vitro and in vivo. Murine hepatic stellate cells, Kupffer cells, and human LX-2 cells were treated with vitamin D analogs, and the profibrotic behavior of these cells was studied. In vivo liver fibrosis was induced using CCl4 until measurable fibrosis was established. Animals were then treated with calcitriol and paricalcitol. Vitamin D and its analogs showed antifibrotic effects in vitro. Treatment with active vitamin D (calcitriol, CAL) and its analogs reduced the protein expression of α-smooth muscle actin (α-SMA) in mHSC. In human LX-2 cells alfacalcidol reduced transforming growth factor-ß (TGF-ß) induced platelet-derived growth factor receptor-ß protein expression and contractility while paricalcitol (PCT), in its equipotent dose to CAL, reduced TGF-ß induced α-SMA protein expression, and ACTA2 and TGF-ß mRNA expression. No effects of a treatment with vitamin D and its analogs were observed in Kupffer cells. In vivo, PCT-treated mice had significantly lower calcium levels than CAL-treated mice. CAL and PCT reduced the hepatic infiltration of CD11b-positive cells and alanine transaminase levels, while PCT but not CAL significantly inhibited fibrosis progression, with a favorable side effect profile in the CCl4 model. We conclude that hypocalcemic vitamin D analogs should be considered in future studies investigating vitamin D for the treatment of liver fibrosis.

Activation of vitamin D receptor attenuates high glucose-induced cellular injury partially dependent on CYP2J5 in murine renal tubule epithelial cell.

AIMS: Vitamin D and its receptor, vitamin D receptor (VDR), have renoprotection effect against diabetic nephropathy (DN). But the exact mechanism has not been fully elucidated. Epoxyeicosatrienoic acids (EETs) are cytochrome P450 (CYP) epoxygenase-derived metabolites of arachidonic acid, protecting against diabetes and DN. Herein, we hypothesized that activation of VDR attenuated high glucose-induced cellular injury in renal tubular epithelial cells partially through up-regulating CYP2J5 expression. MAIN METHODS: Streptozotocin (STZ) was injected to induce diabetic in wild type and Vdr-/- mice. The effects of VDR knockout and an activator of VDR, paricalcitol, on the renal injury were detected. In vitro, a murine kidney proximal tubule epithelial cell line BU.MPT induced by high glucose were treated with or without paricalcitol (30 mM) for 12 h or 24 h. KEY FINDINGS: The expression of CYP2J5 was significantly decreased both in wild type and Vdr-/- diabetic mice induced by STZ. The STZ-induced kidney architecture damage and apoptosis rate in Vdr-/- mice were more severe. In vitro, high glucose treatment strongly reduced the CYP2J5 expression and the synthesis of 14,15-EET in BU.MPT cells. Supplement of 14,15-EET significantly reduced the lactate dehydrogenase (LDH) release induced by high glucose in BU.MPT cells. Furthermore, treatment with paricalcitol attenuated cellular injury and restored the expression of CYP2J5 reduced by high glucose in BU.MPT cells. SIGNIFICANCE: We conclude that activation of VDR attenuates high glucose-induced cellular injury partially dependent on CYP2J5 in murine renal tubule epithelial cells and paricalcitol may represent a potential therapy for DN.

Questioning the Safety of Calcidiol in Hemodialysis Patients.

BACKGROUND: Epidemiological studies have suggested a survival benefit for hemodialysis patients on paricalcitol or calcitriol, but nutritional vitamin D supplementation of patients already on vitamin D receptor (VDR) activators is controversial. METHODS: This observational retrospective cohort study was conducted with prospectively collected data from all consecutive patients with chronic kidney disease (CKD) who underwent hemodialysis under routine clinical practice conditions for two years. RESULTS: Of the 129 patients, 89 were treated with calcidiol, paricalcitol, and/or calcitriol. The patients with any vitamin D formulation had higher serum concentrations of 25-hydroxy vitamin D and fibroblast growth factor-23 and tended to have higher mortality rates (42% vs. 25%, p = 0.07). On subgroup analysis, any calcidiol treatment or calcidiol combined with paricalcitol associated with significantly higher mortality rates than no treatment (47% and 62.5%, p = 0.043 and 0.008, respectively). The association between calcidiol/paricalcitol treatment and elevated mortality remained significant after adjusting for age, sex, diabetes, C-reactive protein, and hemodialysis vintage. Any calcidiol and calcidiol/paricalcitol treatment exhibited a dose-response relationship with mortality (p for trend: 0.002 and 0.005, respectively). CONCLUSIONS: These data draw attention to the hitherto unexplored safety of calcidiol supplementation in patients on hemodialysis, especially in those already on vitamin D. Until clinical trials demonstrate the safety and efficacy of this approach, caution should be exercised when prescribing these patients ≥0.5 calcidiol mg/month.

Quality of Life in Hypoparathyroidism Improves With rhPTH(1-84) Throughout 8 Years of Therapy.

CONTEXT: Calcium and vitamin D treatment does not improve reduced quality of life (QOL) in hypoparathyroidism. Recombinant human (rh) PTH(1-84) therapy improves QOL metrics for up to 5 years. Data on QOL beyond this time point are not available. OBJECTIVES: To evaluate the effects of 8 years of rhPTH(1-84) therapy on QOL and factors associated with long-term benefit. DESIGN: Prospective, open-label trial. SETTING: Referral center. PATIENTS: Twenty patients with hypoparathyoidism. MAIN OUTCOME MEASURES: RAND 36-Item Short Form Health Survey (SF-36). RESULTS: rhPTH therapy led to substantial improvement in five of the eight SF-36 domains [vitality, social functioning (SF), mental health (MH), bodily pain (BP) and general health] and three of these domains (SF, MH, BP) were no longer lower than the reference population. The improvement in the mental component summary (MCS) score was sustained through 8 years, while the physical component summary (PCS) score improved through 6 years. A lower baseline QOL score was associated with greater improvement. A threshold value <238 (MCS) and <245 (PCS) predicted long-term improvement in 90% and 100% of the cohort, respectively. In patients whose calcium supplementation was reduced, MCS and PCS scores improved more than those whose supplementation did not decline to the same extent. Improvement in PCS was greater in patients whose calcitriol dosage was reduced and duration of disease was shorter. CONCLUSIONS: rhPTH(1-84) improves long-term well-being in hypoparathyroidism. The improvements are most prominent in those with impaired SF-36 at baseline and those whose requirements for conventional therapy decreased substantially.