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Xu F, Lu H, Lai T, Lin L, Chen Y. Association between Vitamin D Status and Mortality among Adults with Diabetic Kidney Disease. J Diabetes Res 2022; 2022:9632355. [PMID: 35586117 PMCID: PMC9110229 DOI: 10.1155/2022/9632355] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Accepted: 04/12/2022] [Indexed: 02/05/2023] Open
Abstract
OBJECTIVE Emerging evidence demonstrates that vitamin D status contributes to the incidence of diabetic kidney disease (DKD). However, the causal relationships between vitamin D and mortality among individuals with DKD are inconclusive. Our study is aimed at exploring the relationship between serum 25-hydroxyvitamin D (25(OH)D) concentrations and mortality among adults with DKD. Research Design and Methods. Our study included 1,202 adult participants with DKD from the National Health and Nutrition Examination Survey (NHANES) 2001-2014. Cox and competing-risks regression were used to estimate hazard ratios (HRs) and 95% CIs for associations between 25(OH)D concentrations and survival. RESULTS The overall mean serum 25(OH)D concentration was 55.9 ± 26.3. Vitamin D deficiency (25(OH)D < 50 nmol/l), insufficiency group (50 ≤ 25(OH)D < 75 nmol/l), and sufficiency group (25(OH)D ≥ 75 nmol/l) were observed in 552 (45.9%), 409 (34.0%), and 241 (20.0%) participants, respectively. Higher levels of vitamin D were significantly associated with improved all-cause and nonaccident- and malignant neoplasm-cause mortality among individuals with DKD after adjusting for the potential confounding factors. CONCLUSIONS We observed widespread vitamin D deficiency or insufficiency in DKD patients. Higher 25(OH)D values were significantly correlated with lower risk of mortality after adjusting for confounding variables.
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Affiliation(s)
- Feng Xu
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China
- Clinical Research Center, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China
| | - Hongyu Lu
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China
- Clinical Research Center, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China
| | - Tianwen Lai
- The Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 515041, China
| | - Ling Lin
- Clinical Research Center, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China
- Department of Rheumatology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China
- Department of Rheumatology, Shantou University Medical College, Shantou 515041, China
| | - Yongsong Chen
- Clinical Research Center, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China
- Department of Endocrinology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China
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2
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Bernhardt SM, Borges VF, Schedin P. Vitamin D as a Potential Preventive Agent For Young Women's Breast Cancer. Cancer Prev Res (Phila) 2021; 14:825-838. [PMID: 34244152 DOI: 10.1158/1940-6207.capr-21-0114] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 05/10/2021] [Accepted: 06/30/2021] [Indexed: 11/16/2022]
Abstract
Clinical studies backed by research in animal models suggest that vitamin D may protect against the development of breast cancer, implicating vitamin D as a promising candidate for breast cancer prevention. However, despite clear preclinical evidence showing protective roles for vitamin D, broadly targeted clinical trials of vitamin D supplementation have yielded conflicting findings, highlighting the complexity of translating preclinical data to efficacy in humans. While vitamin D supplementation targeted to high-risk populations is a strategy anticipated to increase prevention efficacy, a complimentary approach is to target transient, developmental windows of elevated breast cancer risk. Postpartum mammary gland involution represents a developmental window of increased breast cancer promotion that may be poised for vitamin D supplementation. Targeting the window of involution with short-term vitamin D intervention may offer a simple, cost-effective approach for the prevention of breast cancers that develop postpartum. In this review, we highlight epidemiologic and preclinical studies linking vitamin D deficiency with breast cancer development. We discuss the underlying mechanisms through which vitamin D deficiency contributes to cancer development, with an emphasis on the anti-inflammatory activity of vitamin D. We also discuss current evidence for vitamin D as an immunotherapeutic agent and the potential for vitamin D as a preventative strategy for young woman's breast cancer.
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Affiliation(s)
- Sarah M Bernhardt
- Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, Oregon.,Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon
| | - Virginia F Borges
- Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado.,Young Women's Breast Cancer Translational Program, University of Colorado Cancer Center, Aurora, Colorado
| | - Pepper Schedin
- Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, Oregon. .,Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.,Young Women's Breast Cancer Translational Program, University of Colorado Cancer Center, Aurora, Colorado
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Pihlstrøm HK, Ueland T, Michelsen AE, Aukrust P, Gatti F, Hammarström C, Kasprzycka M, Wang J, Haraldsen G, Mjøen G, Dahle DO, Midtvedt K, Eide IA, Hartmann A, Holdaas H. Exploring the potential effect of paricalcitol on markers of inflammation in de novo renal transplant recipients. PLoS One 2020; 15:e0243759. [PMID: 33326471 PMCID: PMC7743930 DOI: 10.1371/journal.pone.0243759] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Accepted: 11/29/2020] [Indexed: 11/18/2022] Open
Abstract
Following a successful renal transplantation circulating markers of inflammation may remain elevated, and systemic inflammation is associated with worse clinical outcome in renal transplant recipients (RTRs). Vitamin D-receptor (VDR) activation is postulated to modulate inflammation and endothelial function. We aimed to explore if a synthetic vitamin D, paricalcitol, could influence systemic inflammation and immune activation in RTRs. Newly transplanted RTRs were included in an open-label randomized controlled trial on the effect of paricalcitol on top of standard care over the first post-transplant year. Fourteen pre-defined circulating biomarkers reflecting leukocyte activation, endothelial activation, fibrosis and general inflammatory burden were analyzed in 74 RTRs at 8 weeks (baseline) and 1 year post-engraftment. Mean changes in plasma biomarker concentrations were compared by t-test. The expression of genes coding for the same biomarkers were investigated in 1-year surveillance graft biopsies (n = 60). In patients treated with paricalcitol circulating osteoprotegerin levels increased by 0.19 ng/ml, compared with a 0.05 ng/ml increase in controls (p = 0.030). In graft tissue, a 21% higher median gene expression level of TNFRSF11B coding for osteoprotegerin was found in paricalcitol-treated patients compared with controls (p = 0.026). Paricalcitol treatment did not significantly affect the blood- or tissue levels of any other investigated inflammatory marker. In RTRs, paricalcitol treatment might increase both circulating and tissue levels of osteoprotegerin, a modulator of calcification, but potential anti-inflammatory treatment effects in RTRs are likely very modest. [NCT01694160 (2012/107D)]; [www.clinicaltrials.gov].
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Affiliation(s)
- Hege Kampen Pihlstrøm
- Department of Surgery, Inflammation Medicine and Transplantation, Section of Nephrology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- * E-mail:
| | - Thor Ueland
- Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- K.G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Tromsø, Norway
| | - Annika E. Michelsen
- Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Pål Aukrust
- Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Department of Surgery, Inflammation Medicine and Transplantation, Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Rikshospitalet, Oslo, Norway
| | - Franscesca Gatti
- Department of Pathology, Oslo University Hospital, Oslo, Norway
- K.G. Jebsen Inflammation Research Centre, Laboratory of Immunohistochemistry and Immunopathology, University of Oslo, Oslo, Norway
| | - Clara Hammarström
- Department of Pathology, Oslo University Hospital, Oslo, Norway
- K.G. Jebsen Inflammation Research Centre, Laboratory of Immunohistochemistry and Immunopathology, University of Oslo, Oslo, Norway
| | - Monika Kasprzycka
- Department of Pathology, Oslo University Hospital, Oslo, Norway
- K.G. Jebsen Inflammation Research Centre, Laboratory of Immunohistochemistry and Immunopathology, University of Oslo, Oslo, Norway
| | - Junbai Wang
- Department of Pathology, Oslo University Hospital, Oslo, Norway
| | - Guttorm Haraldsen
- Department of Pathology, Oslo University Hospital, Oslo, Norway
- K.G. Jebsen Inflammation Research Centre, Laboratory of Immunohistochemistry and Immunopathology, University of Oslo, Oslo, Norway
| | - Geir Mjøen
- Department of Surgery, Inflammation Medicine and Transplantation, Section of Nephrology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
| | - Dag Olav Dahle
- Department of Surgery, Inflammation Medicine and Transplantation, Section of Nephrology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
| | - Karsten Midtvedt
- Department of Surgery, Inflammation Medicine and Transplantation, Section of Nephrology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
| | - Ivar Anders Eide
- Division of Medicine, Department of Nephrology, Akershus University Hospital, Oslo, Norway
| | - Anders Hartmann
- Department of Surgery, Inflammation Medicine and Transplantation, Section of Nephrology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Hallvard Holdaas
- Department of Surgery, Inflammation Medicine and Transplantation, Section of Nephrology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
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Wang Y, Yang S, Zhou Q, Zhang H, Yi B. Effects of Vitamin D Supplementation on Renal Function, Inflammation and Glycemic Control in Patients with Diabetic Nephropathy: a Systematic Review and Meta-Analysis. Kidney Blood Press Res 2019; 44:72-87. [PMID: 30808855 DOI: 10.1159/000498838] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/05/2019] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND/AIMS Vitamin D (VD) is widely recognized as renal protective. However, whether VD supplementation provides benefit to patients with diabetic nephropathy (DN) remains controversial. Here, we performed a meta-analysis to systematically evaluate the impact of VD supplementation on indexes of renal function, inflammation and glycemic control in DN patients, and to explore the potential renal protective mechanism of VD. METHODS We searched Pubmed, Embase, Cochrane Library, and three major Chinese biomedical databases (CNKI, WANGFANG and VIP) for randomized controlled trials (RCTs) examining the effects of VD or its analogs in DN patients, published between September 2007 and July 2018. Quality assessment and data extraction were performed independently by two authors, according to the Cochrane systematic review methods. Meta-analysis based on the extracted results were performed via Revman 5.2 software. RESULTS We included 20 RCTs representing 1,464 patients with DN in this meta-analysis. VD supplementation significantly reduced 24-hour urine protein [MD = -0.26; 95% CI (-0.34, -0.17); P < 0.00001; I2 = 95%], UAER [MD = -67.36; 95% CI (-91.96, -42.76); P < 0.00001; I2 = 97%], hs-CRP [MD = -0.69; 95% CI (-0.86,-0.53); P < 0.00001; I2 = 0%], TNF-α [MD = -56.79; 95% CI (-77.05, -36.52); P < 0.00001; I2 = 89%] and IL-6 [MD = -0.73; 95% CI(-1.03, -0.44); P < 0.00001; I2 = 0%]. However, VD supplementation failed to decrease SCr [MD = -0.83; 95% CI (-3.67,2.02); P = 0.57; I2 = 0%] or increase eGFR [MD = 2.13; 95% CI (-2.06, 6.32); P = 0.32; I2 = 0%]. In addition, VD supplementation showed no impact on indexes of glycemic control, such as HbA1c [MD = 0.01; 95% CI (-0.09, 0.11); P = 0.84; I2 = 0%] and FBG [MD = -0.05; 95% CI (-0.29, 0.20); P = 0.70; I2 = 0%]. Analysis of 24-hour urine protein, SCr, eGFR, hs-CRP or HbA1c revealed no difference between subgroups based on the type of VD supplementation, including calcitriol, alfacalcidol and vitamin D3, and the dose or duration of calcitriol usage. CONCLUSION In patients with DN, VD supplementation provides beneficial effects on 24-hour urine protein and inflammation indexes, but not on SCr, eGFR or glycemic control indexes. More RCTs that comprehensively evaluate the impact of VD supplementation on indexes of renal function, inflammation and glycemic control in DN atients are required in order to reach conclusive results.
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Affiliation(s)
- Yangyang Wang
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Shikun Yang
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Qianying Zhou
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Hao Zhang
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Bin Yi
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, China,
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Donate-Correa J, Henríquez-Palop F, Martín-Núñez E, Hernández-Carballo C, Ferri C, Pérez-Delgado N, Muros-de-Fuentes M, Mora-Fernández C, Navarro-González JF. Anti-inflammatory profile of paricalcitol in kidney transplant recipients. Nefrologia 2017; 37:622-629. [PMID: 28623033 DOI: 10.1016/j.nefroe.2017.11.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2016] [Revised: 03/15/2017] [Accepted: 03/27/2017] [Indexed: 11/25/2024] Open
Abstract
BACKGROUND AND OBJECTIVES Paricalcitol, a selective vitamin D receptor activator, is used to treat secondary hyperparathyroidism in kidney transplant patients. Experimental and clinical studies in non-transplant kidney disease patients have found this molecule to have anti-inflammatory properties. In this exploratory study, we evaluated the anti-inflammatory profile of paricalcitol in kidney-transplant recipients. METHODS Thirty one kidney transplant recipients with secondary hyperparathyroidism completed 3 months of treatment with oral paricalcitol (1μg/day). Serum concentrations and gene expression levels of inflammatory cytokines in peripheral blood mononuclear cells were analysed at the beginning and end of the study. RESULTS Paricalcitol significantly decreased parathyroid hormone levels with no changes in calcium and phosphorous. It also reduced serum concentrations of interleukin (IL)-6 and tumour necrosis factor-alpha (TNF-α) by 29% (P<0.05) and 9.5% (P<0.05) compared to baseline, respectively. Furthermore, gene expression levels of IL-6 and TNF-α in peripheral blood mononuclear cells decreased by 14.1% (P<0.001) and 34.1% (P<0.001), respectively. The ratios between pro-inflammatory cytokines (TNF-α and IL-6) and anti-inflammatory cytokines (IL-10), both regarding serum concentrations and gene expression, also experienced a significant reduction. CONCLUSIONS Paricalcitol administration to kidney transplant recipients has been found to have beneficial effects on inflammation, which may be associated with potential clinical benefits.
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Affiliation(s)
- Javier Donate-Correa
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, España; Unidad de Investigación, Hospital Universitario de Canarias, Santa Cruz de Tenerife, España.
| | - Fernando Henríquez-Palop
- Servicio de Nefrología, Hospital Universitario Doctor Negrín, Las Palmas de Gran Canaria, España
| | - Ernesto Martín-Núñez
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, España
| | - Carolina Hernández-Carballo
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, España
| | - Carla Ferri
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, España
| | - Nayra Pérez-Delgado
- Servicio de Análisis Clínicos, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, España
| | - Mercedes Muros-de-Fuentes
- Servicio de Análisis Clínicos, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, España
| | - Carmen Mora-Fernández
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, España
| | - Juan F Navarro-González
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, España; Servicio de Nefrología, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, España.
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Donate-Correa J, Henríquez-Palop F, Martín-Núñez E, Hernández-Carballo C, Ferri C, Pérez-Delgado N, Muros-de-Fuentes M, Mora-Fernández C, Navarro-González JF. Anti-inflammatory profile of paricalcitol in kidney transplant recipients. Nefrologia 2017. [PMID: 28623033 DOI: 10.1016/j.nefro.2017.03.028] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND AND OBJECTIVES Paricalcitol, a selective vitamin D receptor activator, is used to treat secondary hyperparathyroidism in kidney transplant patients. Experimental and clinical studies in non-transplant kidney disease patients have found this molecule to have anti-inflammatory properties. In this exploratory study, we evaluated the anti-inflammatory profile of paricalcitol in kidney-transplant recipients. METHODS Thirty one kidney transplant recipients with secondary hyperparathyroidism completed 3 months of treatment with oral paricalcitol (1μg/day). Serum concentrations and gene expression levels of inflammatory cytokines in peripheral blood mononuclear cells were analysed at the beginning and end of the study. RESULTS Paricalcitol significantly decreased parathyroid hormone levels with no changes in calcium and phosphorous. It also reduced serum concentrations of interleukin (IL)-6 and tumour necrosis factor-alpha (TNF-α) by 29% (P<0.05) and 9.5% (P<0.05) compared to baseline, respectively. Furthermore, gene expression levels of IL-6 and TNF-α in peripheral blood mononuclear cells decreased by 14.1% (P<0.001) and 34.1% (P<0.001), respectively. The ratios between pro-inflammatory cytokines (TNF-α and IL-6) and anti-inflammatory cytokines (IL-10), both regarding serum concentrations and gene expression, also experienced a significant reduction. CONCLUSIONS Paricalcitol administration to kidney transplant recipients has been found to have beneficial effects on inflammation, which may be associated with potential clinical benefits.
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Affiliation(s)
- Javier Donate-Correa
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, España; Unidad de Investigación, Hospital Universitario de Canarias, Santa Cruz de Tenerife, España.
| | - Fernando Henríquez-Palop
- Servicio de Nefrología, Hospital Universitario Doctor Negrín, Las Palmas de Gran Canaria, España
| | - Ernesto Martín-Núñez
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, España
| | - Carolina Hernández-Carballo
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, España
| | - Carla Ferri
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, España
| | - Nayra Pérez-Delgado
- Servicio de Análisis Clínicos, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, España
| | - Mercedes Muros-de-Fuentes
- Servicio de Análisis Clínicos, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, España
| | - Carmen Mora-Fernández
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, España
| | - Juan F Navarro-González
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, España; Servicio de Nefrología, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, España.
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Anti-Inflammatory Effects of Vitamin D on Human Immune Cells in the Context of Bacterial Infection. Nutrients 2016; 8:nu8120806. [PMID: 27973447 PMCID: PMC5188461 DOI: 10.3390/nu8120806] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2016] [Revised: 11/24/2016] [Accepted: 12/07/2016] [Indexed: 12/31/2022] Open
Abstract
Vitamin D induces a diverse range of biological effects, including important functions in bone health, calcium homeostasis and, more recently, on immune function. The role of vitamin D during infection is of particular interest given data from epidemiological studies suggesting that vitamin D deficiency is associated with an increased risk of infection. Vitamin D has diverse immunomodulatory functions, although its role during bacterial infection remains unclear. In this study, we examined the effects of 1,25(OH)₂D₃, the active metabolite of vitamin D, on peripheral blood mononuclear cells (PBMCs) and purified immune cell subsets isolated from healthy adults following stimulation with the bacterial ligands heat-killed pneumococcal serotype 19F (HK19F) and lipopolysaccharide (LPS). We found that 1,25(OH)₂D₃ significantly reduced pro-inflammatory cytokines TNF-α, IFN-γ, and IL-1β as well as the chemokine IL-8 for both ligands (three- to 53-fold), while anti-inflammatory IL-10 was increased (two-fold, p = 0.016) in HK19F-stimulated monocytes. Levels of HK19F-specific IFN-γ were significantly higher (11.7-fold, p = 0.038) in vitamin D-insufficient adults (<50 nmol/L) compared to sufficient adults (>50 nmol/L). Vitamin D also shifted the pro-inflammatory/anti-inflammatory balance towards an anti-inflammatory phenotype and increased the CD14 expression on monocytes (p = 0.008) in response to LPS but not HK19F stimulation. These results suggest that 1,25(OH)₂D₃ may be an important regulator of the inflammatory response and supports further in vivo and clinical studies to confirm the potential benefits of vitamin D in this context.
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Meireles MS, Kamimura MA, Dalboni MA, Giffoni de Carvalho JT, Aoike DT, Cuppari L. Effect of cholecalciferol on vitamin D-regulatory proteins in monocytes and on inflammatory markers in dialysis patients: A randomized controlled trial. Clin Nutr 2016; 35:1251-1258. [DOI: 10.1016/j.clnu.2016.04.014] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2015] [Revised: 03/31/2016] [Accepted: 04/05/2016] [Indexed: 01/08/2023]
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Asemi Z, Samimi M, Siavashani MA, Mazloomi M, Tabassi Z, Karamali M, Jamilian M, Esmaillzadeh A. Calcium-Vitamin D Co-supplementation Affects Metabolic Profiles, but not Pregnancy Outcomes, in Healthy Pregnant Women. Int J Prev Med 2016; 7:49. [PMID: 27076887 PMCID: PMC4809130 DOI: 10.4103/2008-7802.177895] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2015] [Accepted: 11/22/2015] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Pregnancy is associated with unfavorable metabolic profile, which might in turn result in adverse pregnancy outcomes. The current study was designed to evaluate the effects of calcium plus Vitamin D administration on metabolic status and pregnancy outcomes in healthy pregnant women. METHODS This randomized double-blind placebo-controlled clinical trial was performed among 42 pregnant women aged 18-40 years who were at week 25 of gestation. Subjects were randomly allocated to consume either 500 mg calcium-200 IU cholecalciferol supplements (n = 21) or placebo (n = 21) for 9 weeks. Blood samples were obtained at the onset of the study and after 9-week trial to determine related markers. Post-delivery, the newborn's weight, length, and head circumference were measured during the first 24 h after birth. RESULTS Consumption of calcium-Vitamin D co-supplements resulted in a significant reduction of serum high-sensitivity C-reactive protein levels compared with placebo (-1856.8 ± 2657.7 vs. 707.1 ± 3139.4 μg/mL, P = 0.006). We also found a significant elevation of plasma total antioxidant capacity (89.3 ± 118.0 vs. -9.4 ± 164.9 mmol/L, P = 0.03), serum 25-hydroxyvitamin D (2.5 ± 3.5 vs. -1.7 ± 1.7 ng/mL, P < 0.0001), and calcium levels (0.6 ± 0.6 vs. -0.1 ± 0.4 mg/dL, P < 0.0001). The supplementation led to a significant decrease in diastolic blood pressure (-1.9 ± 8.3 vs. 3.1 ± 5.2 mmHg, P = 0.02) compared with placebo. No significant effect of calcium-Vitamin D co-supplements was seen on other metabolic profiles. We saw no significant change of the co-supplementation on pregnancy outcomes as well. CONCLUSIONS Although calcium-Vitamin D co-supplementation for 9 weeks in pregnant women resulted in improved metabolic profiles, it did not affect pregnancy outcomes.
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Affiliation(s)
- Zatollah Asemi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
| | - Mansooreh Samimi
- Department of Gynecology and Obstetrics, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Mehrnush Amiri Siavashani
- Department of Gynecology and Obstetrics, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran
| | - Maryam Mazloomi
- Department of Gynecology and Obstetrics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Zohreh Tabassi
- Department of Gynecology and Obstetrics, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Maryam Karamali
- Department of Gynecology and Obstetrics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mehri Jamilian
- Endocrinology and Metabolism Research Center, Arak University of Medical Sciences, Arak, Iran; Department of Gynecology and Obstetrics, School of Medicine, Arak University of Medical Sciences, Arak, Iran
| | - Ahmad Esmaillzadeh
- Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran; Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran; Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
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Effects of Citral on Lipopolysaccharide-Induced Inflammation in Human Umbilical Vein Endothelial Cells. Inflammation 2015; 39:663-71. [DOI: 10.1007/s10753-015-0292-0] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
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Wamberg L, Pedersen SB, Rejnmark L, Richelsen B. Causes of Vitamin D Deficiency and Effect of Vitamin D Supplementation on Metabolic Complications in Obesity: a Review. Curr Obes Rep 2015; 4:429-40. [PMID: 26353882 DOI: 10.1007/s13679-015-0176-5] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Obese subjects are often characterized by low plasma 25-hydroxy-vitamin D (25OHD) levels. Many explanations for this association have been proposed. Low plasma 25OHD is associated with obesity-related comorbidities such as insulin resistance, type 2 diabetes mellitus, and low-grade inflammation. In this review, we discuss the proposed mechanisms for low 25OHD in obesity and explore the results of recent RCTs on vitamin D (VD) supplementation on obesity and its metabolic complications such as insulin resistance and type 2 diabetes. Although the results from these clinical randomized controlled trials vary, the general picture is that VD treatment of obese individuals does not seem to be an effective treatment of obesity-related metabolic complications.
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Affiliation(s)
- Louise Wamberg
- Department of Internal Medicine and Endocrinology MEA, Aarhus University Hospital, Tage- Hansens Gade 2, DK-8000, Aarhus, Denmark.
| | - Steen B Pedersen
- Department of Internal Medicine and Endocrinology MEA, Aarhus University Hospital, Tage- Hansens Gade 2, DK-8000, Aarhus, Denmark.
| | - Lars Rejnmark
- Department of Internal Medicine and Endocrinology MEA, Aarhus University Hospital, Tage- Hansens Gade 2, DK-8000, Aarhus, Denmark.
| | - Bjørn Richelsen
- Department of Internal Medicine and Endocrinology MEA, Aarhus University Hospital, Tage- Hansens Gade 2, DK-8000, Aarhus, Denmark.
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12
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Afsar B, Agca E, Turk S. Comparison of erythropoietin resistance in hemodialysis patients using calcitriol, cinacalcet, or paricalcitol. J Clin Pharmacol 2015; 55:1280-5. [PMID: 26032009 DOI: 10.1002/jcph.556] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2015] [Accepted: 05/20/2015] [Indexed: 11/07/2022]
Abstract
The erythropoiesis-stimulating agent (ESA) hyporesponsiveness index (EHRI) calculated as the weekly dose of EPO divided by weight (kg) divided by hemoglobin level (g/dL) has been considered useful to assess ESA resistance. Recent evidence suggests that active vitamin D, cinacalcet, and paricalcitol use may be related with lower ESA resistance. We conducted this observational cross-sectional study to investigate ESA resistance calculated by the EHRI among patients using calcitriol, cinacalcet, and paricalcitol. Participants underwent a medical history taken, physical examination, measurement of biochemical analysis, calculation of dialysis adequacy, and EHRI. Sixty-five patients did not receive any treatment regarding vitamin D, paricalcitol, and cinacalcet (group 1), 41 were taking only vitamin D (group 2), 50 were taking only paricalcitol (group 3), 19 were taking only cinacalcet (group 4), and 21 were taking paricalcitol + cinacalcet (group 5). The EHRI values for groups 1, 2, 3, 4, and 5 were 11.36 ± 8.72, 11.58 ± 5.72, 8.29 ± 5.54, 9.49 ± 4.61, and 8.91 ± 4.44 respectively (P =.034). Post hoc analysis showed that the EHRI differed between group 1 and group 3 (P =.017) and between group 2 and group 3 (P =.006). In linear regression analysis, use of paricalcitol was independently associated with EHRI. In conclusion, paricalcitol use was associated with lower EHRI levels as a measure of ESA resistance.
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Affiliation(s)
- Baris Afsar
- Konya Numune State Hospital, Department of Nephrology, Konya, Turkey
| | - Erhan Agca
- Konya Numune State Hospital, Department of Nephrology, Konya, Turkey
| | - Suleyman Turk
- Selcuklu Faculty of Medicine, Selcuk University, Department of Nephrology, Konya, Turkey
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13
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Cozzolino M. Vitamin D: something new under the sun. Clin Kidney J 2015; 5:285-7. [PMID: 25874081 PMCID: PMC4393484 DOI: 10.1093/ckj/sfs080] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2012] [Accepted: 06/11/2012] [Indexed: 12/29/2022] Open
Affiliation(s)
- Mario Cozzolino
- Renal Division, Department of Health Sciences , University of Milan, San Paolo Hospital , Milan , Italy
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14
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Eleftheriadis T, Pissas G, Antoniadi G, Liakopoulos V, Stefanidis I. Factors affecting effectiveness of vaccination against hepatitis B virus in hemodialysis patients. World J Gastroenterol 2014; 20:12018-12025. [PMID: 25232238 PMCID: PMC4161789 DOI: 10.3748/wjg.v20.i34.12018] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2013] [Revised: 01/29/2014] [Accepted: 04/08/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) is a major global health problem. Despite the success of the general measures against blood transmitted infections in hemodialysis (HD) units, the prevalence of HBV infection among the HD patients is still high. Thus vaccination against HBV is indicating in this population. However, compared with the general population the seroprotection achieved in HD patients remains relatively low, at about 70%. In this review patient, HD procedure and vaccine-associated factors that affect the efficacy of HBV vaccination are analyzed. Also alternative routes of HBV vaccine administration as well as new and more immunogenic vaccine formulations are discussed. However, besides scientific progress, vigilance of HD physicians and staff regarding the general measures against the transmission of blood borne infections and the vaccination against HBV is also required for reducing the prevalence of this viral infection.
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15
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Hansen D, Rasmussen K, Rasmussen LM, Bruunsgaard H, Brandi L. The influence of vitamin D analogs on calcification modulators, N-terminal pro-B-type natriuretic peptide and inflammatory markers in hemodialysis patients: a randomized crossover study. BMC Nephrol 2014; 15:130. [PMID: 25112372 PMCID: PMC4136403 DOI: 10.1186/1471-2369-15-130] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2014] [Accepted: 08/07/2014] [Indexed: 12/22/2022] Open
Abstract
Background The risk of cardiovascular disease is tremendously high in dialysis patients. Dialysis patients treated with vitamin D analogs show decreased cardiovascular morbidity and mortality compared with untreated patients. We examined the influence of two common vitamin D analogs, alfacalcidol and paricalcitol, on important cardiovascular biomarkers in hemodialysis patients. Anti-inflammatory effects and the influence on regulators of vascular calcification as well as markers of heart failure were examined. Methods In 57 chronic hemodialysis patients enrolled in a randomized crossover trial comparing paricalcitol and alfacalcidol, we examined the changes in osteoprotegerin, fetuin-A, NT-proBNP, hs-Crp, IL-6 and TNF-α, during 16 weeks of treatment. Results NT-proBNP and osteoprotegerin increased comparably in the paricalcitol and alfacalcidol-treated groups. Fetuin-A increased significantly in the alfacalcidol-treated group compared with the paricalcitol-treated group (difference 32.84 μmol/l (95% C.I.; range 0.21–67.47)) during the first treatment period. No difference was found between the groups during the second treatment period, and IL-6, TNF-α and hs-Crp were unchanged in both treatment groups. Conclusions Paricalcitol and alfacalcidol modulate regulators of vascular calcification. Alfacalcidol may increase the level of the calcification inhibitor fetuin-A. We did not find any anti-inflammatory effect or difference in changes of NT-proBNP. Trial registry ClinicalTrials.gov NCT00469599 May 3 2007.
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Affiliation(s)
- Ditte Hansen
- Department of Nephrology, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
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16
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Al-Daghri NM, Guerini FR, Al-Attas OS, Alokail MS, Alkharfy KM, Draz HM, Agliardi C, Costa AS, Saulle I, Mohammed AK, Biasin M, Clerici M. Vitamin D receptor gene polymorphisms are associated with obesity and inflammosome activity. PLoS One 2014; 9:e102141. [PMID: 25020064 PMCID: PMC4096505 DOI: 10.1371/journal.pone.0102141] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2014] [Accepted: 06/13/2014] [Indexed: 01/29/2023] Open
Abstract
To explore the mechanisms underlying the suggested role of the vitamin D/vitamin D receptor (VDR) complex in the pathogenesis of obesity we performed genetic and immunologic analyses in obese and non-obese Saudi individuals without other concomitant chronic diseases. Genomic DNA was genotyped for gene single nucleotide polymorphisms (SNPs) of VDR by allelic discrimination in 402 obese (body mass index –BMI≥30 kg/m2) and 489 non-obese (BMI<30 kg/m2) Saudis. Q-PCR analyses were performed using an ABI Prism 7000 Sequence Detection System. The inflammosome pathway was analysed by PCR, cytokines and plasma lipopolysaccaride (LPS) concentrations with ELISA assays. Results showed that the VDR SNPs rs731236 (G) (TaqI) and rs1544410 (T) (Bsm-I) minor allele polymorphisms are significantly more frequent in obese individuals (p = 0.009, β = 0.086 and p = 0.028, β = 0.072, respectively). VDR haplotypes identified are positively (GTA) (p = 0.008, β = 1.560); or negatively (ACC) (p = 0.044, β = 0.766) associated with obesity and higher BMI scores. The GTA "risk" haplotype was characterized by an up-regulation of inflammosome components, a higher production of proinflammatory cytokines (p<0.05) and a lower VDR expression. Plasma LPS concentration was also increased in GTA obese individuals (p<0.05), suggesting an alteration of gut permeability leading to microbial translocation. Data herein indicate that polymorphisms affecting the vitamin D/VDR axis play a role in obesity that is associated with an ongoing degree of inflammation, possibly resulting from alterations of gut permeability and microbial translocation. These results could help the definition of VDR fingerprints that predict an increased risk of developing obesity and might contribute to the identification of novel therapeutic strategies for this metabolic condition.
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Affiliation(s)
- Nasser M. Al-Daghri
- Biomarkers Research Program, Biochemistry Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia (KSA)
- Prince Mutaib Chair for Biomarkers of Osteoporosis, College of Science, King Saud University, Riyadh, KSA
- Center of Excellence in Biotechnology Research, King Saud University, Riyadh, KSA
- * E-mail:
| | - Franca R. Guerini
- Don Gnocchi Foundation, ONLUS, Milano and Università degli Studi di Milano, Milano, Italy
| | - Omar S. Al-Attas
- Biomarkers Research Program, Biochemistry Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia (KSA)
- Prince Mutaib Chair for Biomarkers of Osteoporosis, College of Science, King Saud University, Riyadh, KSA
- Center of Excellence in Biotechnology Research, King Saud University, Riyadh, KSA
| | - Majed S. Alokail
- Biomarkers Research Program, Biochemistry Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia (KSA)
- Prince Mutaib Chair for Biomarkers of Osteoporosis, College of Science, King Saud University, Riyadh, KSA
- Center of Excellence in Biotechnology Research, King Saud University, Riyadh, KSA
| | - Khalid M. Alkharfy
- Biomarkers Research Program, Biochemistry Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia (KSA)
- Prince Mutaib Chair for Biomarkers of Osteoporosis, College of Science, King Saud University, Riyadh, KSA
- Clinical Pharmacy Department, College of Pharmacy, King Saud University, Riyadh, KSA
| | - Hossam M. Draz
- Biomarkers Research Program, Biochemistry Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia (KSA)
- INRS-Institute Armand Frappier, University of Quebec, Laval, Quebec, Canada
| | - Cristina Agliardi
- Don Gnocchi Foundation, ONLUS, Milano and Università degli Studi di Milano, Milano, Italy
| | - Andrea S. Costa
- Don Gnocchi Foundation, ONLUS, Milano and Università degli Studi di Milano, Milano, Italy
| | - Irma Saulle
- Department of Biomedical and Clinical Sciences, Università degli Studi di Milano, Milano, Italy
| | - Abdul Khader Mohammed
- Biomarkers Research Program, Biochemistry Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia (KSA)
| | - Mara Biasin
- Department of Biomedical and Clinical Sciences, Università degli Studi di Milano, Milano, Italy
| | - Mario Clerici
- Biomarkers Research Program, Biochemistry Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia (KSA)
- Don Gnocchi Foundation, ONLUS, Milano and Università degli Studi di Milano, Milano, Italy
- Department of Biomedical and Clinical Sciences, Università degli Studi di Milano, Milano, Italy
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Wöbke TK, Sorg BL, Steinhilber D. Vitamin D in inflammatory diseases. Front Physiol 2014; 5:244. [PMID: 25071589 PMCID: PMC4078458 DOI: 10.3389/fphys.2014.00244] [Citation(s) in RCA: 124] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2014] [Accepted: 06/12/2014] [Indexed: 02/06/2023] Open
Abstract
Changes in vitamin D serum levels have been associated with inflammatory diseases, such as inflammatory bowel disease (IBD), rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis (MS), atherosclerosis, or asthma. Genome- and transcriptome-wide studies indicate that vitamin D signaling modulates many inflammatory responses on several levels. This includes (i) the regulation of the expression of genes which generate pro-inflammatory mediators, such as cyclooxygenases or 5-lipoxygenase, (ii) the interference with transcription factors, such as NF-κB, which regulate the expression of inflammatory genes and (iii) the activation of signaling cascades, such as MAP kinases which mediate inflammatory responses. Vitamin D targets various tissues and cell types, a number of which belong to the immune system, such as monocytes/macrophages, dendritic cells (DCs) as well as B- and T cells, leading to individual responses of each cell type. One hallmark of these specific vitamin D effects is the cell-type specific regulation of genes involved in the regulation of inflammatory processes and the interplay between vitamin D signaling and other signaling cascades involved in inflammation. An important task in the near future will be the elucidation of the regulatory mechanisms that are involved in the regulation of inflammatory responses by vitamin D on the molecular level by the use of techniques such as chromatin immunoprecipitation (ChIP), ChIP-seq, and FAIRE-seq.
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Affiliation(s)
- Thea K Wöbke
- Institute of Pharmaceutical Chemistry, Goethe University Frankfurt Frankfurt, Germany
| | - Bernd L Sorg
- Institute of Pharmaceutical Chemistry, Goethe University Frankfurt Frankfurt, Germany
| | - Dieter Steinhilber
- Institute of Pharmaceutical Chemistry, Goethe University Frankfurt Frankfurt, Germany
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18
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Reich KM, Fedorak RN, Madsen K, Kroeker KI. Vitamin D improves inflammatory bowel disease outcomes: Basic science and clinical review. World J Gastroenterol 2014; 20:4934-4947. [PMID: 24803805 PMCID: PMC4009525 DOI: 10.3748/wjg.v20.i17.4934] [Citation(s) in RCA: 82] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2013] [Revised: 11/13/2013] [Accepted: 12/13/2013] [Indexed: 02/06/2023] Open
Abstract
Vitamin D deficiency is commonly diagnosed among patients with inflammatory bowel disease (IBD). Patients with IBD are at risk of low bone density and increased fractures due to low vitamin D levels, long standing disease, and frequent steroid exposures; as a result, it is well established that vitamin D supplementation in this population is important. There is increasing support for the role of vitamin D in strengthening the innate immune system by acting as an immunomodulator and reducing inflammation in experimental and human IBD. The active form of vitamin D, 1,25(OH)D3, acts on T cells to promote T helper (Th)2/regulatory T responses over Th1/Th17 responses; suppresses dendritic cell inflammatory activity; induces antibacterial activity; and regulates cytokine production in favor of an anti-inflammatory response. Murine and human IBD studies support a therapeutic role of vitamin D in IBD. Risk factors for vitamin D deficiency in this population include decreased sunlight exposure, disease duration, smoking, and genetics. Vitamin D normalization is associated with reduced risk of relapse, reduced risk of IBD-related surgeries, and improvement in quality of life. Vitamin D is an inexpensive supplement which has been shown to improve IBD outcomes. However, further research is required to determine optimal serum vitamin D levels which will achieve beneficial immune effects, and stronger evidence is needed to support the role of vitamin D in inducing disease response and remission, as well as maintaining this improvement in patients’ disease states.
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19
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Differential influence of vitamin D analogs on left ventricular mass index in maintenance hemodialysis patients. Int J Artif Organs 2014; 37:118-25. [PMID: 24619898 DOI: 10.5301/ijao.5000289] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/15/2013] [Indexed: 01/02/2023]
Abstract
PURPOSE Secondary hyperparathyroidism (SHPT) is a common feature in maintenance hemodialysis (MHD) patients. Inadequate treatment of SHPT has been associated with cardiovascular complications, and vitamin D therapy might influence the development of cardiovascular diseases. In the present study, we aimed to evaluate the effects of intravenous paricalcitol and calcitriol treatments on left ventricular mass index changes in MHD patients. METHODS We conducted an observational study with a 12-month follow-up duration to compare the outcomes of intravenous paricalcitol and calcitriol treatments in MHD patients. Eighty patients with moderate to severe SHPT were enrolled in the study. All the patients had normalized total serum Ca concentration <10.5 mg/dL, serum calcium-phosphorus product (Ca × P) <75, and parathyroid hormone level (PTH) level ≥300 pg/mL at the begining of the follow-up period. RESULTS The patients were divided into a paricalcitol group (n = 40) and a calcitriol group (n = 40). The demographic, clinical, and biochemical characteristics of the patients were similar at baseline. We observed significantly superior control of SHPT; lesser frequency of hypercalcemia and hyperphosphatemia, and Ca × P level elevations; and interruption of vitamin D treatment in the paricalcitol group. Moreover, we found no significant change in left ventricular mass index in the paricalcitol group, but found a significantly increased left ventricular mass index in the calcitriol group during the follow-up period (from 136.6 ± 35.2 g/m2 to 132.9 ± 40.4 g/m2 vs. from 137.2 ± 30.1 g/m2 to 149.4 ± 31.0 g/m2; p<0.044). CONCLUSION We observed that, compared with calcitriol therapy, paricalcitol therapy reduced the PTH concentrations more effectively without causing hypercalcemia and hyperphosphatemia and might have a substantial beneficial effect on the development of left ventricular hypertrophy.
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20
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Donate-Correa J, Domínguez-Pimentel V, Méndez-Pérez ML, Muros-de-Fuentes M, Mora-Fernández C, Martín-Núñez E, Cazaña-Pérez V, Navarro-González JF. Selective vitamin D receptor activation as anti-inflammatory target in chronic kidney disease. Mediators Inflamm 2014; 2014:670475. [PMID: 24511210 PMCID: PMC3913352 DOI: 10.1155/2014/670475] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2013] [Revised: 11/18/2013] [Accepted: 12/09/2013] [Indexed: 11/29/2022] Open
Abstract
Paricalcitol, a selective vitamin D receptor (VDR) activator used for treatment of secondary hyperparathyroidism in chronic kidney disease (CKD), has been associated with survival advantages, suggesting that this drug, beyond its ability to suppress parathyroid hormone, may have additional beneficial actions. In this prospective, nonrandomised, open-label, proof-of-concept study, we evaluated the hypothesis that selective vitamin D receptor activation with paricalcitol is an effective target to modulate inflammation in CKD patients. Eight patients with an estimated glomerular filtration rate between 15 and 44 mL/min/1.73 m(2) and an intact parathyroid hormone (PTH) level higher than 110 pg/mL received oral paricalcitol (1 μg/48 hours) as therapy for secondary hyperparathyroidism. Nine patients matched by age, sex, and stage of CKD, but a PTH level <110 pg/mL, were enrolled as a control group. Our results show that five months of paricalcitol administration were associated with a reduction in serum concentrations of hs-CRP (13.9%, P < 0.01), TNF-α (11.9%, P = 0.01), and IL-6 (7%, P < 0.05), with a nonsignificant increase of IL-10 by 16%. In addition, mRNA expression levels of the TNFα and IL-6 genes in peripheral blood mononuclear cells decreased significantly by 30.8% (P = 0.01) and 35.4% (P = 0.01), respectively. In conclusion, selective VDR activation is an effective target to modulate inflammation in CKD.
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Affiliation(s)
- J. Donate-Correa
- Research Unit, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain
- GEENDIAB (Grupo Español para el Estudio de la Nefropatía Diabética) and REDINREN (RD12/0021/0019), Spain
| | - V. Domínguez-Pimentel
- Nephrology Service, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain
| | - M. L. Méndez-Pérez
- Nephrology Service, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain
| | - M. Muros-de-Fuentes
- GEENDIAB (Grupo Español para el Estudio de la Nefropatía Diabética) and REDINREN (RD12/0021/0019), Spain
- Clinical Analysis Service, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain
| | - C. Mora-Fernández
- Research Unit, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain
- GEENDIAB (Grupo Español para el Estudio de la Nefropatía Diabética) and REDINREN (RD12/0021/0019), Spain
| | - E. Martín-Núñez
- Research Unit, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain
| | - V. Cazaña-Pérez
- Research Unit, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain
| | - J. F. Navarro-González
- Research Unit, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain
- GEENDIAB (Grupo Español para el Estudio de la Nefropatía Diabética) and REDINREN (RD12/0021/0019), Spain
- Nephrology Service, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain
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Cozzolino M, Stucchi A, Rizzo MA, Soldati L, Cusi D, Ciceri P, Brenna I, Elli F, Gallieni M. Reprint of: Vitamin D receptor activation and prevention of arterial ageing. Nutr Metab Cardiovasc Dis 2013; 23 Suppl 1:S31-S36. [PMID: 23199645 DOI: 10.1016/j.numecd.2012.11.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2011] [Revised: 03/20/2012] [Accepted: 03/21/2012] [Indexed: 01/02/2023]
Abstract
In chronic kidney disease (CKD) patients, cardiovascular (CV) morbidity and mortality rate is higher than in the general population, because of frequently concomitant hypertension, peripheral vascular disease, heart failure, vascular calcification (VC), diabetes and mineral bone disease. Recently, another important factor associated to CV risk in CKD has been deeply investigated: vitamin D deficiency. Vitamin D Receptors (VDRs) are present in several systems and tissues and VDR activation is associated to positive effects, resulting in better blood pressure control and prevention of diabetic nephropathy. Unfortunately, the natural, non-selective vitamin D receptor activator (VDRA), calcitriol, is associated to higher serum calcium and phosphate levels, thus worsening CV risk in CKD. Recent data showed that the selective VDRA paricalcitol might have ameliorative CV effects. The potential positive impact of the use of paricalcitol on diabetic nephropathy, cardiac disease, hypertension, and VC may open new paths in the fight against CV disease in CKD patients.
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Affiliation(s)
- M Cozzolino
- Renal Division, DMCO, University of Milan, San Paolo Hospital, Via A. di Rudinì 8, 20142 Milan, Italy.
| | - A Stucchi
- Renal Division, DMCO, University of Milan, San Paolo Hospital, Via A. di Rudinì 8, 20142 Milan, Italy
| | - M A Rizzo
- Nephrology and Dialysis Unit, San Carlo Borromeo Hospital, Milan, Italy
| | - L Soldati
- Renal Division, DMCO, University of Milan, San Paolo Hospital, Via A. di Rudinì 8, 20142 Milan, Italy
| | - D Cusi
- Renal Division, DMCO, University of Milan, San Paolo Hospital, Via A. di Rudinì 8, 20142 Milan, Italy
| | - P Ciceri
- Renal Division, DMCO, University of Milan, San Paolo Hospital, Via A. di Rudinì 8, 20142 Milan, Italy
| | - I Brenna
- Renal Division, DMCO, University of Milan, San Paolo Hospital, Via A. di Rudinì 8, 20142 Milan, Italy
| | - F Elli
- Renal Division, DMCO, University of Milan, San Paolo Hospital, Via A. di Rudinì 8, 20142 Milan, Italy
| | - M Gallieni
- Nephrology and Dialysis Unit, San Carlo Borromeo Hospital, Milan, Italy
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Icardi A, Paoletti E, De Nicola L, Mazzaferro S, Russo R, Cozzolino M. Renal anaemia and EPO hyporesponsiveness associated with vitamin D deficiency: the potential role of inflammation. Nephrol Dial Transplant 2013; 28:1672-9. [PMID: 23468534 DOI: 10.1093/ndt/gft021] [Citation(s) in RCA: 91] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Resistance to erythropoiesis-stimulating agents (ESAs) has been observed in a considerable proportion of patients with chronic kidney disease (CKD) and it is reportedly associated with adverse outcomes, such as increased cardiovascular morbidity, faster progression to end-stage renal disease (ESRD) and all-cause mortality. The major causes of ESA resistance include chronic inflammation producing suppressive cytokines of early erythroid progenitor proliferation. In addition, pro-inflammatory cytokines stimulate hepcidin synthesis thus reducing iron availability for late erythropoiesis. Recent studies showing an association in deficiencies of the vitamin D axis with low haemoglobin (Hb) levels and ESA resistance suggest a new pathophysiological co-factor of renal anaemia. The administration of either native or active vitamin D has been associated with an improvement of anaemia and reduction in ESA requirements. Notably, these effects are not related to parathyroid hormone (PTH) values and seem to be independent on PTH suppression. Another possible explanation may be that calcitriol directly stimulates erythroid progenitors; however, this proliferative effect by extra-renal activation of 1α-hydroxylase enzyme is only a hypothesis. The majority of studies concerning vitamin D deficiency or supplementation, and degree of renal anaemia, point out the prevalent role of inflammation in the mechanism underlying these associations. Immune cells express the vitamin D receptor (VDR) which in turn is involved in the modulation of innate and adaptive immunity. VDR activation inhibits the expression of inflammatory cytokines in stromal and accessory cells and up-regulates the lymphocytic release of interleukin-10 (IL-10) exerting both anti-inflammatory activity and proliferative effects on erythroid progenitors. In CKD patients, vitamin D deficiency may stimulate immune cells within the bone marrow micro-environment to produce cytokines, inducing impaired erythropoiesis. Immune activation involves the reticuloendothelial system, increasing hepcidin synthesis and functional iron deficiency. Consequences of this inflammatory cascade are erythropoietin (EPO) resistance and anaemia. Given the key role of inflammation in the response to EPO, the therapeutic use of agents with anti-cytokines properties, such as vitamin D and paricalcitol, may provide benefit in the prevention/treatment of ESA hyporesponsiveness.
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Affiliation(s)
- Andrea Icardi
- Nephrology and Dialysis Unit, La Colletta and Villa Scassi Hospitals-ASL 3, Arenzano and Genoa, Italy
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Izquierdo MJ, Cavia M, Muñiz P, de Francisco ALM, Arias M, Santos J, Abaigar P. Paricalcitol reduces oxidative stress and inflammation in hemodialysis patients. BMC Nephrol 2012. [PMID: 23186077 PMCID: PMC3520723 DOI: 10.1186/1471-2369-13-159] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Treatment with selective vitamin D receptor activators such as paricalcitol have been shown to exert an anti-inflammatory effect in patients on hemodialysis, in addition to their action on mineral metabolism and independently of parathyroid hormone (PTH) levels. The objective of this study was to evaluate the additional antioxidant capacity of paricalcitol in a clinical setting. METHODS The study included 19 patients with renal disease on hemodialysis, of whom peripheral blood was obtained for analysis at baseline and three months after starting intravenous paricalcitol treatment. The following oxidizing and inflammatory markers were quantified: malondialdehyde (MDA), nitrites and carbonyl groups, indoleamine 2,3-dioxygenase (IDO), tumor necrosis factor alfa (TNF-α), interleukin-6 (IL-6), interleukin-18 (IL-18) and C-reactive protein (CRP). Of the antioxidants and anti-inflammatory markers, superoxide dismutase (SOD), catalase, reduced glutathione (GSH), thioredoxin, and interleukin-10 (IL-10) levels were obtained. RESULTS Baseline levels of oxidation markers MDA, nitric oxide and protein carbonyl groups significantly decreased after three months on paricalcitol treatment, while levels of GSH, thioredoxin, catalase and SOD activity significantly increased. After paricalcitol treatment, levels of the inflammatory markers CRP, TNF-α, IL-6 and IL-18 were significantly reduced in serum and the level of anti-inflammatory cytokine IL-10 was increased. CONCLUSIONS In renal patients undergoing hemodialysis, paricalcitol treatment significantly reduces oxidative stress and inflammation, two well known factors leading to cardiovascular damage.
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Affiliation(s)
- María Jesús Izquierdo
- Nephrology Service, Complejo Asistencial Universitario de Burgos, C/ Fuenteovejuna 138, Burgos, 09006, Spain.
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Yang L, Ma J, Zhang X, Fan Y, Wang L. Protective role of the vitamin D receptor. Cell Immunol 2012; 279:160-6. [PMID: 23246677 DOI: 10.1016/j.cellimm.2012.10.002] [Citation(s) in RCA: 62] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2012] [Revised: 09/16/2012] [Accepted: 10/17/2012] [Indexed: 02/06/2023]
Abstract
Vitamin D receptor (VDR) is found in most tissues, not just those participating in the classic actions of vitamin D such as bone, gut, and kidney. The nonclassic actions are therefore potential targets for the active metabolite of vitamin D, 1,25(OH)₂D₃. This review is intended to highlight the actions of VDR in role of protection. Medline is searched for articles describing actions of VDR on secondary hyperparathyroidism, diabetic nephropathy, hypertension and atherosclerosis. VDR exerts its protective activities through the following mechanisms: inhibition of renin-angiotensin system (RAS); regulation of proliferation and differentiation; reduction of proteinuria; anti-inflammation and anti-fibrosis. The nonclassic actions of VDR provide a number of potential new clinical applications for 1,25(OH)₂D₃ and its analogs. We believe 1,25(OH)₂D₃/VDR can be of particular value in the prevention of kidney-related diseases.
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Affiliation(s)
- Lina Yang
- Department of Nephrology, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning, PR China
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Calcitriol downregulates TNF-α and IL-6 expression in cultured placental cells from preeclamptic women. Cytokine 2012; 61:245-50. [PMID: 23103122 DOI: 10.1016/j.cyto.2012.10.001] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2012] [Revised: 08/17/2012] [Accepted: 10/01/2012] [Indexed: 11/21/2022]
Abstract
Placenta is an important source and target of hormones that contribute to immunological tolerance and maintenance of pregnancy. In preeclampsia (PE), placental calcitriol synthesis is low; whereas pro-inflammatory cytokines levels are increased, threatening pregnancy outcome. Previously, we showed that calcitriol inhibits Th-1 cytokines under experimental inflammatory conditions in normal trophoblasts. However, a study of the regulation of inflammatory cytokines by calcitriol in trophoblasts from a natural inflammatory condition, such as PE, is still lacking. Therefore, the aim of the present study was to investigate calcitriol effects upon TNF-α, IFN-γ, IL-6 and IL-1β in cultured placental cells from preeclamptic women by using qPCR and ELISA. Placentas were collected after cesarean section from preeclamptic women and enriched trophoblastic preparations were cultured in the absence or presence of different calcitriol concentrations during 24h. In these cell cultures, pro-inflammatory cytokines TNF-α and IL-6 secretion and mRNA expression were downregulated by calcitriol (P<0.05). No significant effects of calcitriol upon IFN-γ and IL-1β were observed. In addition, basal expression of TNF-α, IL-6 and IL-1β decreased as the cells formed syncytia. Our study supports an important autocrine/paracrine role of placental calcitriol in controlling adverse immunological responses at the feto-maternal interface, particularly in gestational pathologies associated with exacerbated inflammatory responses such as preeclampsia.
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Cozzolino M, Stucchi A, Rizzo MA, Soldati L, Cusi D, Ciceri P, Brenna I, Elli F, Gallieni M. Vitamin D receptor activation and prevention of arterial ageing. Nutr Metab Cardiovasc Dis 2012; 22:547-552. [PMID: 22633189 DOI: 10.1016/j.numecd.2012.03.010] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2011] [Revised: 03/20/2012] [Accepted: 03/21/2012] [Indexed: 01/10/2023]
Abstract
In chronic kidney disease (CKD) patients, cardiovascular (CV) morbidity and mortality rate is higher than in the general population, because of frequently concomitant hypertension, peripheral vascular disease, heart failure, vascular calcification (VC), diabetes and mineral bone disease. Recently, another important factor associated to CV risk in CKD has been deeply investigated: vitamin D deficiency. Vitamin D Receptors (VDRs) are present in several systems and tissues and VDR activation is associated to positive effects, resulting in better blood pressure control and prevention of diabetic nephropathy. Unfortunately, the natural, non-selective vitamin D receptor activator (VDRA), calcitriol, is associated to higher serum calcium and phosphate levels, thus worsening CV risk in CKD. Recent data showed that the selective VDRA paricalcitol might have ameliorative CV effects. The potential positive impact of the use of paricalcitol on diabetic nephropathy, cardiac disease, hypertension, and VC may open new paths in the fight against CV disease in CKD patients.
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Affiliation(s)
- M Cozzolino
- Renal Division, DMCO, University of Milan, San Paolo Hospital, Via A. di Rudinì 8, Milan, Italy.
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Zhu H, Guo D, Li K, Pedersen-White J, Stallmann-Jorgensen IS, Huang Y, Parikh S, Liu K, Dong Y. Increased telomerase activity and vitamin D supplementation in overweight African Americans. Int J Obes (Lond) 2011; 36:805-9. [PMID: 21986705 DOI: 10.1038/ijo.2011.197] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE We aimed to investigate whether vitamin D supplementation modulates peripheral blood mononuclear cell (PBMC) telomerase activity in overweight African Americans. DESIGN A double blind, randomized and placebo-controlled clinical trial (#NCT01141192) was recently conducted. SUBJECTS AND METHODS African-American adults were randomly assigned to either the placebo, or the vitamin D group (60,000 IU per month (equivalent to ~2000 IU per day) oral vitamin D3 supplementation). Fresh PBMCs were collected from 37 subjects (18 in the placebo group and 19 in the vitamin D group), both at baseline and 16 weeks. PBMC telomerase activity was measured by the telomeric repeat amplification protocol. RESULTS Serum 25 hydroxyvitamin D levels increased from 40.7±15.7 at baseline to 48.1±17.5 nmol l(-1) at posttest (P=0.004) in the placebo group, and from 35.4±11.3 at baseline to 103.7±31.5 nmol l(-1) at posttests (P<0.0001) in the vitamin D group. In the vitamin D group, PBMC telomerase activity increased by 19.2% from baseline (1.56±0.29 absorbance reading unit (AU)) to posttest (1.86±0.42 AU, P<0.0001). The significance persisted after controlling for age, sex and body mass index (P=0.039). PBMC telomerase activity in the placebo group did not change from baseline (1.43±0.26 AU) to posttest (1.46±0.27 AU, P=0.157). CONCLUSION Vitamin D supplementation significantly increased PBMC telomerase activity in overweight African Americans. Our data suggest that vitamin D may improve telomere maintenance and prevent cell senescence and counteract obesity-induced acceleration of cellular aging.
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Affiliation(s)
- H Zhu
- Georgia Prevention Institute, Department of Pediatrics, Georgia Health Sciences University, Augusta, GA 30912, USA.
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Gravellone L, Rizzo MA, Martina V, Mezzina N, Regalia A, Gallieni M. Vitamin d receptor activators and clinical outcomes in chronic kidney disease. Int J Nephrol 2011; 2011:419524. [PMID: 21647319 PMCID: PMC3106992 DOI: 10.4061/2011/419524] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2011] [Accepted: 03/14/2011] [Indexed: 01/27/2023] Open
Abstract
Vitamin D deficiency appears to be an underestimated risk factor for cardiovascular disease in patients with chronic kidney disease. Evidence from both basic science and clinical studies supports the possible protective role of vitamin D beyond its effect on mineral metabolism. Toxicity of pharmacologic doses of active vitamin D metabolites, in particular calcitriol, is mainly due to the possibility of positive calcium and phosphorus balance. Therefore, vitamin D analogs have been developed, which suppress PTH secretion and synthesis with reduced calcemic and phosphatemic effects. Observational studies suggest that in hemodialysis patients the use of a vitamin D receptor (VDR) activator, such as calcitriol, doxercalciferol, paricalcitol, or alfacalcidol, is associated with a reduced mortality when compared with nonusers of any VDR activator. In this article the existing literature on the topic is reviewed, although a more robust answer to the question of whether or not VDR activators have beneficial effects in hemodialysis patients will hopefully come from a randomized controlled trial.
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Affiliation(s)
- Luciana Gravellone
- Specialty School of Nephrology, DMCO, University of Milano Via di Rudini 8, 20142 Milano, Italy
- Nephrology and Dialysis Unit, San Carlo Borromeo Hospital, Via Pio II 3, 20153 Milano, Italy
| | - Maria Antonietta Rizzo
- Specialty School of Nephrology, DMCO, University of Milano Via di Rudini 8, 20142 Milano, Italy
- Nephrology and Dialysis Unit, San Carlo Borromeo Hospital, Via Pio II 3, 20153 Milano, Italy
| | - Valentina Martina
- Specialty School of Nephrology, DMCO, University of Milano Via di Rudini 8, 20142 Milano, Italy
- Nephrology and Dialysis Unit, San Carlo Borromeo Hospital, Via Pio II 3, 20153 Milano, Italy
| | - Nicoletta Mezzina
- Specialty School of Nephrology, DMCO, University of Milano Via di Rudini 8, 20142 Milano, Italy
- Nephrology and Dialysis Unit, San Carlo Borromeo Hospital, Via Pio II 3, 20153 Milano, Italy
| | - Anna Regalia
- Nephrology and Dialysis Unit, San Carlo Borromeo Hospital, Via Pio II 3, 20153 Milano, Italy
| | - Maurizio Gallieni
- Specialty School of Nephrology, DMCO, University of Milano Via di Rudini 8, 20142 Milano, Italy
- Nephrology and Dialysis Unit, San Carlo Borromeo Hospital, Via Pio II 3, 20153 Milano, Italy
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Abstract
Vitamin D deficiency results in abnormal mineralization of bones and has resulted in prevention programs for children with supplementation when they are breast fed. Further activities of vitamin D relate to defence of microbial infections, e.g. tuberculosis, prevention of cancer, contractility of muscle cells and counteraction of congestive heart failure. Given early reports in the 1960s on deleterious effects of vitamin D supplementation in rodents, that is ectopic media ossification of arterial vessels, a pro-atherogenic function had been anticipated for humans as well. However, cross-sectional studies reveal that vitamin D deficiency in humans is associated with elevated blood pressure and propagation of atherogenesis. These contradictory findings on the progression of atherosclerosis may be reconciled by dissecting the activation mechanism(s) of vitamin D in rodents versus humans. Notably, novel findings convincingly indicate that vitamin D exerts anti-inflammatory effects. In conclusion, vitamin D supplementation in adults may be regarded as simple means with few potential side effects to prevent atherogenesis or halt its progression and combat arterial hypertension. Adjustment of vitamin D dosing regimens is required in patients with chronic kidney disease; however, prospective clinical trials are urgently needed to guide these recommendations with evidence.
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