Mortality in Hemodialysis Patients with COVID-19, the Effect of Paricalcitol or Calcimimetics

Background. In COVID-19 patients, low serum vitamin D (VD) levels have been associated with severe acute respiratory failure and poor prognosis. In regular hemodialysis (HD) patients, there is VD deficiency and markedly reduced calcitriol levels, which may predispose them to worse outcomes of COVID-19 infection. Some hemodialysis patients receive treatment with drugs for secondary hyperparathyroidism, which have well known pleiotropic effects beyond mineral metabolism. The aim of this study was to evaluate the impact of VD status and the administration of active vitamin D medications, used to treat secondary hyperparathyroidism, on survival in a cohort of COVID-19 positive HD patients. Methods. A cross-sectional retrospective observational study was conducted from 12 March to 21 May 2020 in 288 HD patients with positive PCR for SARS-CoV2. Patients were from 52 different centers in Spain. Results. The percent of HD patients with COVID-19 was 6.1% (288 out of 4743). Mortality rate was 28.4% (81/285). Three patients were lost to follow-up. Serum 25(OH)D (calcidiol) level was 17.1 [10.6–27.5] ng/mL and was not significantly associated to mortality (OR 0.99 (0.97–1.01), p = 0.4). Patients receiving active vitamin D medications (16/94 (17%) vs. 65/191(34%), p = 0.003), including calcimimetics (4/49 (8.2%) vs. 77/236 (32.6%), p = 0.001), paricalcitol or calcimimetics (19/117 (16.2%) vs. 62/168 (36.9%); p < 0.001), and also those on both paricalcitol and calcimimetics, to treat secondary hyperparathyroidism (SHPTH) (1/26 (3.8%) vs. 80/259 (30.9%), p < 0.001) showed a lower mortality rate than patients receiving no treatment with either drug. Multivariate Cox regression analysis confirmed this increased survival. Conclusions. Our findings suggest that the use of paricalcitol, calcimimetics or the combination of both, seem to be associated with the improvement of survival in HD patients with COVID-19. No correlation was found between serum VD levels and prognosis or outcomes in HD patients with COVID-19. Prospective studies and clinical trials are needed to support these findings.     

维生素D受体基因起始密码子多态性与体力活动对青春期女童骨量增长的交互作用

目的 探讨维生素D受体(VDR)基因起始密码子(Fok I位点)多态性与体力活动对青春期女童骨量增长的交互作用.方法 选择228名9～11.5岁未月经初潮的健康女童进行2年追踪,应用双能X线骨密度仪检测对象追踪前后全身、左侧近端股骨(包括股骨颈、大转子、粗隆间和华氏三角区)和L1～L4腰椎骨密度,应用PCR-RFLP技术检测VDR基因Fok I位点多态性.结果 本次研究的有效观察人数为176名.Fok I位点多态性与骨密度(BMD)2年增长率没有关联.在低体力活动水平(<1197 kJ/d)时,FF基因型女童左侧近端股骨骨密度(THBMD)和股骨颈骨密度(FNBMD)增长率低于Ff+ff基因型女童,差异有统计学意义;体力活动与THBMD和FNBMD增长率有关联,但仅限于FF基因型女童.结论 VDR基因Fok I多态性与体力活动水平对青春期女童骨量增长存在交互作用,低体力活动水平的FF基因型女童可能是骨量增长较低的危险人群,体力活动能促进FF基因型女童骨量增长.     

维生素D及其受体在肝硬化病情评估及治疗中的作用

肝脏是维生素D产生的主要场所,不同病因所致的慢性肝损伤,终会影响维生素D代谢而导致维生素D缺乏,从而加速肝病本身的进展。近期研究证实,肝硬化患者体内维生素D缺乏程度与肝硬化的严重程度、并发症的发生关系密切。介绍了维生素D及其受体在肝硬化病情评估及治疗中的作用,指出维生素D不仅有助于评估肝硬化病情的严重程度,也有可能作为肝硬化治疗的新切入点并成为重要的辅助药物。     

Conversion of vitamin D3 to 1alpha,25-dihydroxyvitamin D3 in human skin equivalents

These results demonstrate for the first time that human keratinocytes under in vivo-like conditions have the capacity of the enzymatic hydroxylation of vitamin D3 to hormonally active calcitriol (1alpha,25(OH)2D3). Supplementation of the culture medium with bovine serum albumin (BSA) up to 1.5%) (w/v) amplifies the conversion of vitamin D3 to 1alpha,25(OH)2D3. The maximum turnover rate of this reaction at 780 nM vitamin D3 in presence of 1.0% (w/v) BSA amounts to approximately 3 pmol 1alpha,25(OH)2D3 per 10(6) cells after 6 h of incubation. The hydroxylation of vitamin D3 to 1alpha,25(OH)2D3 is inhibited by the P-450 oxidase inhibitor ketoconazole. The generation of 1alpha,25(OH)2D3 from vitamin D3 has an apparent Michaelis constant (Km) of 2.3x10(-6) M. The intrinsic conversion of vitamin D3 to biologically active 1alpha,25(OH)2D3 may be of importance for the regulation of proliferation and differentiation of keratinocytes.     

Vitamin D and skin: new aspects for dermatology

Abstract:  It has been shown that epidermal keratinocytes have the capacity for the UVB-induced photochemical conversion of 7-dehydrocholesterol to vitamin D₃, and also for the enzymatically controlled hydroxylation of the photolysis product. This metabolic loop results in the formation of the biologically active final product 1α,25-dihydroxyvitamin D₃ (1α,25(OH)₂D₃, calcitriol). The epidermal synthesis of calcitriol is of fundamental relevance because calcitriol regulates important cellular functions in keratinocytes and immunocompetent cells. Because of their anti-proliferative and prodifferentiating effects, calcitriol and other vitamin D analogs are highly efficient in the treatment of psoriasis vulgaris. In addition, the known therapeutic effect of UVB light therapy in the treatment of psoriasis may, at least in part, be mediated via UVB-induced synthesis of calcitriol. Increasing evidence now indicates that cutaneous vitamin D synthesis is of great importance for the prevention of a broad variety of diseases, including various malignancies. It has been postulated that cancer mortality could be reduced via careful UV exposure or, more safely, via oral substitution with vitamin D. These new findings must be taken into account when establishing new sun protection guidelines for the prevention of skin cancer. In addition, better understanding of the metabolism of vitamin D in the skin has opened up new perspectives for the therapeutic application of vitamin D analogs, e.g. in inflammatory skin diseases.     

Cord Serum Calcitriol Inversely Correlates with Maternal Blood Pressure in Urinary Tract Infection-Affected Pregnancies: Sex-Dependent Immune Implications

Urinary tract infections (UTI) during pregnancy are frequently associated with hypertensive disorders, increasing the risk of perinatal morbidity. Calcitriol, vitamin D₃’s most active metabolite, has been involved in blood pressure regulation and prevention of UTIs, partially through modulating vasoactive peptides and antimicrobial peptides, like cathelicidin. However, nothing is known regarding the interplay between placental calcitriol, cathelicidin, and maternal blood pressure in UTI-complicated pregnancies. Here, we analyzed the correlation between these parameters in pregnant women with UTI and with normal pregnancy (NP). Umbilical venous serum calcitriol and its precursor calcidiol were significantly elevated in UTI. Regardless of newborn’s sex, we found strong negative correlations between calcitriol and maternal systolic and diastolic blood pressure in the UTI cohort (p < 0.002). In NP, this relationship was observed only in female-carrying mothers. UTI-female placentas showed higher expression of cathelicidin and CYP27B1, the calcitriol activating-enzyme, compared to male and NP samples. Accordingly, cord-serum calcitriol from UTI-female neonates negatively correlated with maternal bacteriuria. Cathelicidin gene expression positively correlated with gestational age in UTI and with newborn anthropometric parameters. Our results suggest that vitamin D deficiency might predispose to maternal cardiovascular risk and perinatal infections especially in male-carrying pregnancies, probably due to lower placental CYP27B1 and cathelicidin expression.     

维生素D3促进大鼠胃癌血管新生机制的研究

为探讨维生素D3促进大鼠胃癌血管新生的机制,取Wistar大鼠12只作为空白对照(Ⅰ组),饲常规饲料;另将120只经饮水摄入N-甲基-N′-亚硝基-N-亚硝基胍(MNNG,150mg/L)4周制作大鼠胃癌模型,之后均分为3组:Ⅱ组为对照(MNNG),饲常规饲料;Ⅲ、Ⅳ组分别饲以1,25-二羟基维生素D3添加饲料(2.5μg/kg和5.0μg/kg).于实验16、32周处死动物,处死前行活体心血管内墨汁灌注.进行血管内皮细胞生长因子(VEGF)免疫组织化学染色和微血管密度测定.结果显示,实验16周Ⅳ组VEGF表达和微血管密度明显高于MNNG组(P＜0.05),至实验32周达到更为显著水平(P＜0.01);VEGF表达与微血管密度密切相关(r=0.604,P＜0.01).提示VEGF表达增强可能是1,25(OH)2D3促进大鼠胃癌血管新生的机制之一.     

Comparison of cutaneous tolerance and efficacy of calcitriol 3 microg g(-1) ointment and tacrolimus 0.3 mg g(-1) ointment in chronic plaque psoriasis involving facial or genitofemoral areas: a double-blind, randomized controlled trial

BACKGROUND: Two nonsteroidal topical agents, calcitriol and tacrolimus, have been reported to be effective and safe for psoriatic lesions on sensitive areas. However, no comparative studies between calcitriol and tacrolimus have been reported. OBJECTIVES: To compare the tolerability and efficacy of calcitriol 3 microg g(-1) and tacrolimus 0.3 mg g(-1) ointment in chronic plaque psoriasis affecting facial and genitofemoral regions. METHODS: This is a double-blind, parallel, 6-week study of 50 patients who were randomized in a 1 : 1 ratio to apply calcitriol or tacrolimus twice daily. The primary efficacy variable was the mean reduction of the target area score (TAS), and the secondary efficacy variable was the percentage of patients with the Physician's Global Assessment (PGA) score of 5 (clear) and 4 (almost clear) at the end of the study. RESULTS: Both calcitriol and tacrolimus were well tolerated. Although calcitriol induced perilesional erythema in a statistically significant higher proportion of patients than tacrolimus (55% vs. 16% at week 6; P < 0.05), it did not necessitate treatment discontinuation. At the end of the study, tacrolimus was significantly more effective than calcitriol based on a significant reduction of mean TAS (67% vs. 51%; P < 0.05) as well as more patients achieving complete or almost complete clearance by PGA (60% vs. 33%; P < 0.05). CONCLUSIONS: Both calcitriol 3 microg g(-1) and tacrolimus 0.3 mg g(-1) are safe and well-tolerated therapeutic agents in the treatment of psoriasis in sensitive areas. Tacrolimus demonstrated a more effective clinical outcome compared with calcitriol.