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Eissa H, Abdelsalam EM, Mokbel SA, Elhadedy NH, Khalil RM, AbdElfattah AAM, Abdel Ghaffar DM, El Nashar EM, Hassan AH, Al-Zahrani NS, Aldahhan RA, Yassin NAE. Vitamin D supplementation as a prophylactic therapy in the management of pre-eclampsia: Focus on VEGF, Ki67, oxidative stress markers in correlation to placental ultra structure. Life Sci 2025; 372:123605. [PMID: 40194761 DOI: 10.1016/j.lfs.2025.123605] [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: 01/28/2025] [Revised: 03/21/2025] [Accepted: 04/01/2025] [Indexed: 04/09/2025]
Abstract
BACKGROUND Pre-eclampsia (PE) is a progressive hypertension condition that manifests in the second or third trimester of pregnancy and causes significant proteinuria. A lack of vitamin D (Vit. D) is linked to different pregnancy problems, including impaired placental development. Vitamin D has been shown to enhance fetal growth and lower the incidence of PE. AIM OF THE WORK To better understand the pathophysiological mechanisms behind the PE disease and the therapeutic approaches used to manage it, this study examines the role of Vit. D in placental ischemia and its regulatory effects in Nitro L-arginine Methyl Ester (L-NAME) animal model of PE. METHODS Fifty female rats in the estrus stage were mated with 30 male rats. Thirty female rats were pregnant and divided into three equal groups: control, Preeclampsia group (PE); using L-NAME for induction of PE, and Vit. D group from 7th day then induction by L-NAME at 10th day till end of pregnancy. Mean arterial Bp, proteinuria, oxidative stress markers, histological structure and immunohistochemical expression of Ki67 and VEGF, Morphometric study, and transmission electron microscopy(TEM) were assessed. The results of the current study suggested that, Vit. D supplementation could lower blood pressure, reduce oxidative stress, and restore angiogenic balance through vascular endothelial growth factor (VEGF) and Ki67. CONCLUSION For the first time, we conclude that vitamin D supplementation may not only have direct effects on blood pressure regulation and angiogenic hemostasis but also recover placental function, actually contributing to the prevention or management of PE.
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Affiliation(s)
- Hanan Eissa
- Department of Clinical Pharmacology, Mansoura University, Mansoura, Egypt.
| | | | - Somaia A Mokbel
- Department of Clinical Pharmacology, Mansoura University, Mansoura, Egypt.
| | - Nada H Elhadedy
- Department of Clinical Pathology, Mansoura University, Mansoura, Egypt
| | - Rania M Khalil
- Department of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt.
| | - Amany AbdElfattah Mohamed AbdElfattah
- Department of Medical Histology & Cell Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt; Department of Basic Medical Sciences, Faculty of Medicine, King Salman International University, South Sinai, Egypt.
| | - Dalia M Abdel Ghaffar
- Department of Physiology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
| | - Eman Mohamad El Nashar
- Department of Anatomy, College Medicine, King Khalid University, Abha 62529, Saudi Arabia.
| | - Alshehri Hanan Hassan
- Endocrinology and Diabetes Section, Internal Medicine Department, College of Medicine, King Khalid University, Abha 62529, Saudi Arabia.
| | - Norah Saeed Al-Zahrani
- Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha 62529, Saudi Arabia.
| | - Rashid A Aldahhan
- Department of Anatomy, College of Medicine, Imam Abdulrahman Bin Faisal University, P.O. Box 2114, Dammam 31451, Saudi Arabia.
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Mahmoudi L, Izadpanah P, Asadi S. The effect of calcitriol and cholecalciferol on inflammatory markers in periprocedural myocardial injury: A randomized controlled trial. Medicine (Baltimore) 2025; 104:e42103. [PMID: 40228253 PMCID: PMC11999415 DOI: 10.1097/md.0000000000042103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Accepted: 03/28/2025] [Indexed: 04/16/2025] Open
Abstract
BACKGROUND Inflammation is an important factor in the development of cardiac injury during and after percutaneous coronary intervention (PCI). Vitamin D receptors play a significant role in the cardiovascular system and have anti-inflammatory effects. Hence, our goal was to evaluate the impact of calcitriol and cholecalciferol as vitamin D receptors agonists on inflammatory biomarkers in patients who are undergoing elective PCI. METHODS In this controlled clinical trial, patients undergoing elective PCI were randomly assigned to receive either calcitriol and cholecalciferol or were placed in the control group from July 2021 to November 2022. Calcitriol and cholecalciferol were administered at doses of 1 mcg and 300,000 international units, respectively, before the procedure. High-sensitive C-reactive protein (hs-CRP) was evaluated as the main inflammatory biomarker and other relevant clinical and laboratory data were also included. RESULTS During the study, 180 patients were allocated into three groups, each consisting of 60 patients, with a mean age of 62.26 ± 8.73 years. The prevalence of the underlying conditions was not different among the groups. After 24 hours, hs-CRP levels were lower (P = .012), and a significantly lower increase from baseline was observed (P = .003) in the group that received calcitriol. However, no significant differences were observed in Troponin I and creatine kinase-MB levels (P > .05). CONCLUSIONS Administration of calcitriol was associated with significantly lower levels of hs-CRP, the main cardiac inflammatory marker, in patients undergoing elective PCI. Further clinical studies with a larger sample size are needed to assess the clinical impact of this anti-inflammatory effect.
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Affiliation(s)
- Laleh Mahmoudi
- Department of Clinical Pharmacy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Peyman Izadpanah
- Department of Cardiovascular Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Sara Asadi
- Department of Clinical Pharmacy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
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Strubbe M, David K, Peene B, Eeckhout B, Van der Schueren B, Decallonne B, Vangoitsenhoven R, Vanderschueren D, Antonio L. No longer to be ignored: Hypophosphatemia following intravenous iron administration. Rev Endocr Metab Disord 2025; 26:125-135. [PMID: 39648248 DOI: 10.1007/s11154-024-09926-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/01/2024] [Indexed: 12/10/2024]
Abstract
Intravenous iron supplementation is increasingly used to safely and effectively correct iron deficiency anemia, but some formulations are linked to a renal phosphate wasting syndrome which is mediated by fibroblast growth factor 23. Unawareness among prescribers and the nonspecific clinical symptoms of hypophosphatemia result in underreporting of this complication. Even though it is often an asymptomatic and self-limiting condition, accumulating evidence from case reports and dedicated randomized controlled trials show that IV iron induced hypophosphatemia may be associated with clinical symptoms. If hypophosphatemia is not recognized and treated, a metabolic bone disease phenotype may develop, pathophysiologically reminiscent of hypophosphatemic rickets as seen in X-linked hypophosphatemic rickets or oncogenic osteomalacia. This syndrome is particularly, but not uniquely, associated with formulations containing ferric carboxymaltose, probably due to specific chemical characteristics of its carbohydrate moiety. Risk factors include repeated infusion, severity of iron deficiency, as well as normal kidney function. Coexisting vitamin D deficiency or hyperparathyroidism increase the risk of metabolic bone disease. Complications can be easily prevented by an early diagnosis and switching to another IV iron formulation. In this review, we describe the epidemiology and pathophysiology of this condition, to raise awareness among prescribing clinicians.
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Affiliation(s)
- Matthijs Strubbe
- Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium
| | - Karel David
- Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium
| | - Bernard Peene
- Department of Endocrinology, Ziekenhuis Geel, Geel, Belgium
| | - Bert Eeckhout
- Department of Endocrinology, Ziekenhuis Geel, Geel, Belgium
| | - Bart Van der Schueren
- Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium
- Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Brigitte Decallonne
- Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium
- Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Roman Vangoitsenhoven
- Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium
- Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Dirk Vanderschueren
- Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium
- Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Leen Antonio
- Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium.
- Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium.
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Devraj K, Kulkarni O, Liebner S. Regulation of the blood-brain barrier function by peripheral cues in health and disease. Metab Brain Dis 2024; 40:61. [PMID: 39671124 PMCID: PMC11645320 DOI: 10.1007/s11011-024-01468-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Accepted: 09/12/2024] [Indexed: 12/14/2024]
Abstract
The blood-brain barrier (BBB) is formed by microvascular endothelial cells which are ensembled with pericytes, astrocytes, microglia and neurons in the neurovascular unit (NVU) that is crucial for neuronal function. Given that the NVU and the BBB are highly dynamic and regulated structures, their integrity is continuously challenged by intrinsic and extrinsic factors. Herein, factors from peripheral organs such as gonadal and adrenal hormones may influence vascular function also in CNS endothelial cells in a sex- and age-dependent manner. The communication between the periphery and the CNS likely takes place in specific areas of the brain among which the circumventricular organs have a central position due to their neurosensory or neurosecretory function, owing to physiologically leaky blood vessels. In acute and chronic pathological conditions like liver, kidney, pulmonary disease, toxins and metabolites are generated that reach the brain via the circulation and may directly or indirectly affect BBB functionality via the activation of the immunes system. For example, chronic kidney disease (CKD) currently affects more than 840 million people worldwide and is likely to increase along with western world comorbidities of the cardio-vascular system in continuously ageing societies. Toxins leading to the uremic syndrome, may further lead to neurological complications such as cognitive impairment and uremic encephalopathy. Here we summarize the effects of hormones, toxins and inflammatory reactions on the brain vasculature, highlighting the urgent demand for mechanistically exploring the communication between the periphery and the CNS, focusing on the BBB as a last line of defense for brain protection.
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Affiliation(s)
- Kavi Devraj
- Department of Biological Sciences, Birla Institute of Technology & Science, Pilani, Hyderabad, 500078, Telangana, India.
| | - Onkar Kulkarni
- Metabolic Disorders and Neuroscience Research Laboratory, Department of Pharmacy, Birla Institute of Technology & Science, Pilani, Hyderabad, 500078, Telangana, India
| | - Stefan Liebner
- Institute of Neurology (Edinger Institute), University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany.
- Excellence Cluster Cardio-Pulmonary Institute (CPI), Partner Site Frankfurt, Frankfurt am Main, Germany.
- German Center for Cardiovascular Research (DZHK), Partner Site Frankfurt/Mainz, Frankfurt, Germany.
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Shen B, Liu B, Wang Y, Wang R, Gu D. Severe Vitamin D Deficiency is Associated with Mortality Risk in Critically Ill Patients with Acute Kidney Injury. Int J Gen Med 2024; 17:5153-5162. [PMID: 39539929 PMCID: PMC11559243 DOI: 10.2147/ijgm.s477114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2024] [Accepted: 10/08/2024] [Indexed: 11/16/2024] Open
Abstract
Purpose Deficiency in vitamin D is associated with adverse outcomes in several health conditions. However, the specific impact of vitamin D levels on mortality in acute kidney injury (AKI) patients remains inadequately explored. This study aims to investigate the association between serum vitamin D concentrations and mortality risk in critically ill patients diagnosed with AKI. We hypothesize that severe vitamin D deficiency is associated with an increased risk of 90-day all-cause mortality in these patients. Patients and Methods This study retrospectively enrolled 259 adult AKI patients admitted to the intensive care unit (ICU) at The Fifth Clinical Medical College of Henan University of Chinese Medicine (Zhengzhou People's Hospital) between July 2021 and June 2023. Based on 25-hydroxyvitamin D (25-OHD) levels, they were categorized into 4 groups: severe deficiency (<10 ng/mL), deficiency (10-20 ng/mL), insufficiency (20-30 ng/mL), and sufficiency (>30 ng/mL). Multivariate survival analysis using Cox's regression model was used to analyze the impact of vitamin D concentrations on the 90-day all-cause mortality risk after controlling for potential confounders. Results The 90-day all-cause mortality rate was the highest in patients with severe deficiency (50.8%), followed by those with deficiency (35.0%), insufficiency (23.9%), and sufficiency (12.2%). Multivariate Cox regression showed that compared with sufficiency, severe deficiency (HR=3.34, 95% CI: 1.14-9.77; P=0.03) was independently associated with a higher risk of 90-day all-cause mortality, but deficiency and insufficiency were not significantly associated with 90-day all-cause mortality risk. Conclusion Severe vitamin D deficiency (<10 ng/mL) significantly increases the risk of mortality in AKI patients, underlining the need for monitoring and potentially supplementing vitamin D in this population.
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Affiliation(s)
- Beili Shen
- The Fifth Clinical Medical College of Henan University of Chinese Medicine (Zhengzhou People’s Hospital), Zhengzhou, Henan, 450003, People’s Republic of China
| | - Bianling Liu
- The Fifth Clinical Medical College of Henan University of Chinese Medicine (Zhengzhou People’s Hospital), Zhengzhou, Henan, 450003, People’s Republic of China
| | - Yanhui Wang
- The Fifth Clinical Medical College of Henan University of Chinese Medicine (Zhengzhou People’s Hospital), Zhengzhou, Henan, 450003, People’s Republic of China
| | - Rui Wang
- The Fifth Clinical Medical College of Henan University of Chinese Medicine (Zhengzhou People’s Hospital), Zhengzhou, Henan, 450003, People’s Republic of China
| | - Dongfeng Gu
- The Fifth Clinical Medical College of Henan University of Chinese Medicine (Zhengzhou People’s Hospital), Zhengzhou, Henan, 450003, People’s Republic of China
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Renteria KM, Constantine E, Teoh CM, Cooper A, Lozano N, Bauer S, Koh GY. Combination of vitamin D 3 and fructooligosaccharides upregulates colonic vitamin D receptor in C57BL/6J mice and affects anxiety-related behavior in a sex-specific manner. Nutr Res 2024; 125:16-26. [PMID: 38432179 DOI: 10.1016/j.nutres.2024.02.003] [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: 10/02/2023] [Revised: 02/07/2024] [Accepted: 02/08/2024] [Indexed: 03/05/2024]
Abstract
Depression and anxiety disorders are among the most common mental health disorders that affect US adults today, frequently related to vitamin D (VD) insufficiency. Along with VD, growing evidence suggests gut microbiota likely play a role in neuropsychiatric disorders. Here, we investigated if modulation of gut microbiota would disrupt host VD status and promote behaviors related to depression and anxiety in adult mice. Six-week-old male and female C57BL/6J mice (n = 10/mice/group) were randomly assigned to receive (1) control diet (CTR), control diet treated with antibiotics (AB), control diet with total 5000 IU of VD (VD), VD treated with antibiotics (VD + AB), VD supplemented with 5% w/w fructooligosaccharides (FOS; VF), and VF diet treated with antibiotics (VF + AB), respectively, for 8 weeks. Our study demonstrated that VD status was not affected by antibiotic regimen. VD alone ameliorates anxiety-related behavior in female mice, and that combination with FOS (i.e., VF) did not further improve the outcome. Male mice, in contrast, exhibit greater anxiety with VF, but not VD, when compared with CTR mice. Colonic VD receptor was elevated in VF-treated mice in both sexes, compared with CTR, which was positively correlated to colonic TPH1, a rate-limiting enzyme for serotonin synthesis. Taken together, our data indicate that the effect of VF on anxiety-related behavior is sex-specific, which may partially be attributed to the activation of colonic VD signaling and subsequent serotonin synthesis. The synergistic or additive effect of VD and FOS on mood disorders remained to be investigated.
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Affiliation(s)
- Karisa M Renteria
- Nutrition and Foods Program, School of Family and Consumer Sciences, Texas State University, San Marcos, TX 78666, USA
| | - Ethan Constantine
- Department of Biology, Texas State University, San Marcos, TX 78666, USA
| | - Chin May Teoh
- Nutrition and Foods Program, School of Family and Consumer Sciences, Texas State University, San Marcos, TX 78666, USA
| | - Analynn Cooper
- Nutrition and Foods Program, School of Family and Consumer Sciences, Texas State University, San Marcos, TX 78666, USA
| | - Nissi Lozano
- Nutrition and Foods Program, School of Family and Consumer Sciences, Texas State University, San Marcos, TX 78666, USA
| | - Spenser Bauer
- Nutrition and Foods Program, School of Family and Consumer Sciences, Texas State University, San Marcos, TX 78666, USA
| | - Gar Yee Koh
- Nutrition and Foods Program, School of Family and Consumer Sciences, Texas State University, San Marcos, TX 78666, USA.
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Hasan M, Reyer H, Oster M, Trakooljul N, Ponsuksilli S, Magowan E, Fischer DC, Wimmers K. Exposure to artificial ultraviolet-B light mediates alterations on the hepatic transcriptome and vitamin D metabolism in pigs. J Steroid Biochem Mol Biol 2024; 236:106428. [PMID: 37984748 DOI: 10.1016/j.jsbmb.2023.106428] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Revised: 10/28/2023] [Accepted: 11/17/2023] [Indexed: 11/22/2023]
Abstract
In the currently prevailing pig husbandry systems, the vitamin D status is almost exclusively dependent on dietary supply. Additional endogenous vitamin D production after exposure to ultraviolet-B (UVB) light might allow the animals to utilize minerals in a more efficient manner, as well as enable the production of functional vitamin D-enriched meat for human consumption. In this study, growing pigs (n = 16) were subjected to a control group or to a daily narrowband UVB exposure of 1 standard erythema dose (SED) for a period of 9 weeks until slaughter at a body weight of 105 kg. Transcriptomic profiling of liver with emphasis on the associated effects on vitamin D metabolism due to UVB exposure were evaluated via RNA sequencing. Serum was analyzed for vitamin D status and health parameters such as minerals and biochemical markers. The serum concentration of calcidiol, but not calcitriol, was significantly elevated in response to UVB exposure after 17 days on trial. No effects of UVB exposure were observed on growth performance and blood test results. At slaughter, the RNA sequencing analyses following daily UVB exposure revealed 703 differentially expressed genes (DEGs) in liver tissue (adjusted p-value < 0.01). Results showed that molecular pathways for vitamin D synthesis (CYP2R1) rather than cholesterol synthesis (DHCR7) were preferentially initiated in liver. Gene enrichment (p < 0.05) was observed for reduced cholesterol/steroid biosynthesis, SNARE interactions in vesicular transport, and CDC42 signaling. Taken together, dietary vitamin D supply can be complemented via endogenous production after UVB exposure in pig husbandry, which could be considered in the development of functional foods.
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Affiliation(s)
- Maruf Hasan
- Research Institute for Farm Animal Biology (FBN), Dummerstorf, Germany
| | - Henry Reyer
- Research Institute for Farm Animal Biology (FBN), Dummerstorf, Germany
| | - Michael Oster
- Research Institute for Farm Animal Biology (FBN), Dummerstorf, Germany
| | - Nares Trakooljul
- Research Institute for Farm Animal Biology (FBN), Dummerstorf, Germany
| | | | - Elizabeth Magowan
- Agri-Food and Biosciences Institute, Large Park, Hillsborough, Co Down, BT26 6DR, United Kingdom
| | - Dagmar-Christiane Fischer
- Department of Pediatrics, Rostock University Medical Center, Ernst-Heydemann-Str. 8, 18057 Rostock, Germany
| | - Klaus Wimmers
- Research Institute for Farm Animal Biology (FBN), Dummerstorf, Germany; Faculty of Agricultural and Environmental Sciences, University Rostock, Rostock, Germany.
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8
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Dusso A, Bauerle KT, Zhang RM, Bernal-Mizrachi C. Vitamin D and renal disease. FELDMAN AND PIKE'S VITAMIN D 2024:587-618. [DOI: 10.1016/b978-0-323-91338-6.00029-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Yang TA, Chen JY, Lin CA, Chen YC, Yu W, Huang HY, Xiong XJ, Li WC. Sex differences in the association between vitamin D and early-stage chronic kidney disease: A population-based study. Nutr Res 2023; 117:48-55. [PMID: 37473660 DOI: 10.1016/j.nutres.2023.05.004] [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: 12/27/2022] [Revised: 05/15/2023] [Accepted: 05/16/2023] [Indexed: 07/22/2023]
Abstract
Vitamin D deficiency (VDD) is commonly observed in people with late-stage chronic kidney disease (CKD) and end-stage renal disease; it has also been associated with the progression of kidney disease. We hypothesized that VDD played a role in early-stage chronic kidney disease as well. Thus, this cross-sectional study aimed to evaluate the association between serum 25-hydroxyvitamin D concentration and CKD stages 1 through 3 (early-stage CKD) in a relatively healthy population in China. A total of 3142 Chinese individuals were included in this cross-sectional study. VDD was observed in 108 (5.6%) males and 307 (25.33%) females. We found a significant inverse association between serum 25(OH)D concentration with CKD stages in both sexes. Furthermore, VDD was associated with CKD stages 1 through 3 in males (adjusted odds ratio, 15.84; 95% confidence interval, 7.85-31.98; P < .001), but not in females. Vitamin D status should be evaluated in people who are newly diagnosed with CKD stages 1 through 3 or decreased estimated glomerular filtration rate, especially in males.
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Affiliation(s)
- Ting-An Yang
- Department of Family Medicine, Chang-Gung Memorial Hospital, Linkou Branch, Taoyuan City 333423, Taiwan; Department of Family Medicine, New Taipei Municipal TuCheng Hospital (Built and Operated by Chang Gung Medical Foundation), New Taipei City 236017, Taiwan
| | - Jau-Yuan Chen
- Department of Family Medicine, Chang-Gung Memorial Hospital, Linkou Branch, Taoyuan City 333423, Taiwan; College of Medicine, Chang Gung University, Taoyuan City 333323, Taiwan
| | - Chieh-An Lin
- Department of Family Medicine, Chang-Gung Memorial Hospital, Linkou Branch, Taoyuan City 333423, Taiwan
| | - Yi-Chuan Chen
- Department of Family Medicine, Chang-Gung Memorial Hospital, Linkou Branch, Taoyuan City 333423, Taiwan; College of Medicine, Chang Gung University, Taoyuan City 333323, Taiwan
| | - Wei Yu
- Department of Health Management, Xiamen Chang-Gung Hospital, Xiamen, China
| | - Hsiung Ying Huang
- Department of Pulmonary and Critical Care Medicine, Xiamen Chang-Gung Hospital, Xiamen, China
| | - Xue-Jie Xiong
- Department of Oncology, Xiamen Chang-Gung Hospital, Xiamen, China
| | - Wen-Cheng Li
- Department of Family Medicine, Chang-Gung Memorial Hospital, Linkou Branch, Taoyuan City 333423, Taiwan; College of Medicine, Chang Gung University, Taoyuan City 333323, Taiwan; Department of Health Management, Xiamen Chang-Gung Hospital, Xiamen, China.
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Mandal SK, Tare M, Deepa PR. COVID-19 infection and metabolic comorbidities: Mitigating role of nutritional sufficiency and drug - nutraceutical combinations of vitamin D. HUMAN NUTRITION & METABOLISM 2023; 31:200179. [PMID: 38620788 PMCID: PMC9762046 DOI: 10.1016/j.hnm.2022.200179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 12/12/2022] [Accepted: 12/14/2022] [Indexed: 12/24/2022]
Abstract
The vulnerability of human health is amplified in recent times with global increase in non-communicable diseases (due to lifestyle changes and environmental insults) and infectious diseases (caused by newer pathogens and drug-resistance strains). Clinical management of diseases is further complicated by disease severity caused by other comorbid factors. Drug-based therapy may not be the sole approach, particularly in scenarios like the COVID-19 pandemic, where there is no specific drug against SARS-CoV-2. Nutritional interventions are significant in armouring human populations in disease prevention, and as adjunctive therapy for disease alleviation. Amidst ongoing clinical trials to determine the efficacy of Vit. D against infections and associated complications, this review examines the pleiotropic benefits of nutritional adequacy of vitamin D (Vit. D) in combating viral infections (COVID-19), its severity and complications due to co-morbidities (obesity, diabetes, stroke and Kawasaki disease), based on research findings and clinical studies. Supplements of Vit. D in combination with other nutrients, and drugs, are suggested as promising preventive-health and adjunct-treatment strategies in the clinical management of viral infections with metabolic comorbidities.
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Affiliation(s)
- Sumit Kumar Mandal
- Department of Biological Sciences, Birla Institute of Technology and Science, Pilani, Pilani Campus, Rajasthan, India
| | - Meghana Tare
- Department of Biological Sciences, Birla Institute of Technology and Science, Pilani, Pilani Campus, Rajasthan, India
| | - P R Deepa
- Department of Biological Sciences, Birla Institute of Technology and Science, Pilani, Pilani Campus, Rajasthan, India
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Megalin and Vitamin D Metabolism—Implications in Non-Renal Tissues and Kidney Disease. Nutrients 2022; 14:nu14183690. [PMID: 36145066 PMCID: PMC9506339 DOI: 10.3390/nu14183690] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Revised: 09/02/2022] [Accepted: 09/06/2022] [Indexed: 11/17/2022] Open
Abstract
Megalin is an endocytic receptor abundantly expressed in proximal tubular epithelial cells and other calciotropic extrarenal cells expressing vitamin D metabolizing enzymes, such as bone and parathyroid cells. The receptor functions in the uptake of the vitamin D-binding protein (DBP) complexed to 25 hydroxyvitamin D3 (25(OH)D3), facilitating the intracellular conversion of precursor 25(OH)D3 to the active 1,25 dihydroxyvitamin D3 (1,25(OH)2D3). The significance of renal megalin-mediated reabsorption of 25(OH)D3 and 1,25(OH)2D3 has been well established experimentally, and other studies have demonstrated relevant roles of extrarenal megalin in regulating vitamin D homeostasis in mammary cells, fat, muscle, bone, and mesenchymal stem cells. Parathyroid gland megalin may regulate calcium signaling, suggesting intriguing possibilities for megalin-mediated cross-talk between calcium and vitamin D regulation in the parathyroid; however, parathyroid megalin functionality has not been assessed in the context of vitamin D. Within various models of chronic kidney disease (CKD), megalin expression appears to be downregulated; however, contradictory results have been observed between human and rodent models. This review aims to provide an overview of the current knowledge of megalin function in the context of vitamin D metabolism, with an emphasis on extrarenal megalin, an area that clearly requires further investigation.
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Ding R, Jiang Y, Yang Y, Shi Y, Ji Y, Zhen T, Fu Z, Bao X, Tan J, Zhang S, Li J, Xing K, Zhou X, Zhu S. Calcitriol ameliorates renal injury with high-salt diet-induced hypertension by upregulating GLIS2 expression and AMPK/mTOR-regulated autophagy. Gene 2022; 820:146239. [PMID: 35114278 DOI: 10.1016/j.gene.2022.146239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Revised: 11/03/2021] [Accepted: 01/18/2022] [Indexed: 11/24/2022]
Abstract
The goal of the present study was to investigate the protective effect of calcitriol on high-salt diet-induced hypertension. The hypertension rat model was established by a long-term high-salt diet (8% NaCl). Rats were treated with calcitriol, losartan, or their combination. Histological staining was used to confirm renal pathology. Global transcriptome analysis of renal tissues was performed, and the mechanism of the therapeutic effect of calcitriol was analysed by functional annotation and pathway analysis of the differentially expressed genes (DEGs) as well as by Western blotting analysis. The core genes for potential therapeutic regulation were identified through the coexpression gene network. For in vitro HK-2 cell experiments, small interfering RNA (siRNA) was used to knockdown key a transcription factor (TF) Glis2 to validate the therapeutic target of calcitriol. MAPK1 and CXCL12 expression was downregulated and the apoptosis pathway was significantly enriched by calcitriol treatment. The western blotting results showed that calcitriol treatment increased AMPK phosphorylation and decreased downstream mTOR phosphorylation, which was accompanied by a decrease in autophagy protein p62 expression and an increase in LC3-II/I expression. GLIS2 was identified as a specific therapeutic target for calcitriol. GLIS2 expression was upregulated by calcitriol and confirmed by HK-2 cells in vitro. Our omics data show that calcitriol can alleviate oxidative stress and fibrosis. Moreover, calcitriol can regulate the CXCL12/ERK1/2 cascade to inhibit the inflammatory response and renal cell apoptosis and induce renal autophagy through the AMPK/mTOR pathway. Our study partially elucidate the pathogenesis and treatment mechanism underlying hypertension, and provide new insights into the treatment of hypertension.
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Affiliation(s)
- Ruifeng Ding
- School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China
| | - Yufeng Jiang
- Department of Nephrology, Shuguang Hospital, Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200021, China; Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, Shanghai, China
| | - Yi Yang
- Cinoasia Institute, Shanghai 200438, China
| | - Yong Shi
- Cinoasia Institute, Shanghai 200438, China
| | - Yang Ji
- Cinoasia Institute, Shanghai 200438, China
| | | | | | - Xunxia Bao
- Cinoasia Institute, Shanghai 200438, China
| | - Jia Tan
- School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China
| | - Shuyong Zhang
- School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China
| | - Jiahui Li
- School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China
| | | | - Xinli Zhou
- School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China.
| | - Sibo Zhu
- School of Life Sciences, Fudan University, Shanghai 200438, China.
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13
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Oristrell J, Oliva JC, Casado E, Subirana I, Domínguez D, Toloba A, Balado A, Grau M. Vitamin D supplementation and COVID-19 risk: a population-based, cohort study. J Endocrinol Invest 2022; 45:167-179. [PMID: 34273098 PMCID: PMC8285728 DOI: 10.1007/s40618-021-01639-9] [Citation(s) in RCA: 84] [Impact Index Per Article: 28.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Accepted: 07/12/2021] [Indexed: 12/15/2022]
Abstract
PURPOSE To analyze the associations between cholecalciferol or calcifediol supplementation, serum 25-hydroxyvitamin D (25OHD) levels and COVID-19 outcomes in a large population. METHODS All individuals ≥ 18 years old living in Barcelona-Central Catalonia (n = 4.6 million) supplemented with cholecalciferol or calcifediol from April 2019 to February 2020 were compared with propensity score-matched untreated controls. Outcome variables were SARS-CoV2 infection, severe COVID-19 and COVID-19 mortality occuring during the first wave of the pandemic. Demographical data, comorbidities, serum 25OHD levels and concomitant pharmacological treatments were collected as covariates. Associations between cholecalciferol or calcifediol use and outcome variables were analyzed using multivariate Cox proportional regression. RESULTS Cholecalciferol supplementation (n = 108,343) was associated with slight protection from SARS-CoV2 infection (n = 4352 [4.0%] vs 9142/216,686 [4.2%] in controls; HR 0.95 [CI 95% 0.91-0.98], p = 0.004). Patients on cholecalciferol treatment achieving 25OHD levels ≥ 30 ng/ml had lower risk of SARS-CoV2 infection, lower risk of severe COVID-19 and lower COVID-19 mortality than unsupplemented 25OHD-deficient patients (56/9474 [0.6%] vs 96/7616 [1.3%]; HR 0.66 [CI 95% 0.46-0.93], p = 0.018). Calcifediol use (n = 134,703) was not associated with reduced risk of SARS-CoV2 infection or mortality in the whole cohort. However, patients on calcifediol treatment achieving serum 25OHD levels ≥ 30 ng/ml also had lower risk of SARS-CoV2 infection, lower risk of severe COVID-19, and lower COVID-19 mortality compared to 25OHD-deficient patients not receiving vitamin D supplements (88/16276 [0.5%] vs 96/7616 [1.3%]; HR 0.56 [CI 95% 0.42-0.76], p < 0.001). CONCLUSIONS In this large, population-based study, we observed that patients supplemented with cholecalciferol or calcifediol achieving serum 25OHD levels ≥ 30 ng/ml were associated with better COVID-19 outcomes.
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Affiliation(s)
- J Oristrell
- Internal Medicine Service, Corporació Sanitària Parc Taulí, Parc Taulí s/n, 08208, Sabadell, Barcelona, Catalonia.
- Institut d'Investigació i Innovació I3PT, Sabadell, Catalonia.
- Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Catalonia.
| | - J C Oliva
- Institut d'Investigació i Innovació I3PT, Sabadell, Catalonia
| | - E Casado
- Rheumatology Service, Corporació Sanitària Parc Taulí, Parc Taulí s/n, 08208, Sabadell, Barcelona, Catalonia.
| | - I Subirana
- CIBER of Epidemiology and Public Health (CIBERESP), Barcelona, Catalonia
- Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Catalonia
| | - D Domínguez
- Agència de Qualitat i Avaluació Sanitària, Generalitat de Catalunya, Barcelona, Catalonia
| | - A Toloba
- Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Catalonia
| | - A Balado
- Internal Medicine Service, Corporació Sanitària Parc Taulí, Parc Taulí s/n, 08208, Sabadell, Barcelona, Catalonia
| | - M Grau
- CIBER of Epidemiology and Public Health (CIBERESP), Barcelona, Catalonia
- Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Catalonia
- Department of Medicine, University of Barcelona, Barcelona, Catalonia
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14
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Dusso AS, Bauerle KT, Bernal-Mizrachi C. Non-classical Vitamin D Actions for Renal Protection. Front Med (Lausanne) 2021; 8:790513. [PMID: 34950686 PMCID: PMC8688743 DOI: 10.3389/fmed.2021.790513] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Accepted: 11/15/2021] [Indexed: 11/17/2022] Open
Abstract
Chronic Kidney Disease (CKD), a disorder that affects 11% of the world's population, is characterized by an acceleration in skeletal, immune, renal, and cardiovascular aging that increases the risk of cardiovascular mortality by 10- to 20-fold, compared to that in individuals with normal renal function. For more than two decades, the progressive impairment in renal capacity to maintain normal circulating levels of the hormonal form of vitamin D (1,25-dihydroxyvitamin D or calcitriol) was considered the main contributor to the reduced survival of CKD patients. Accordingly, calcitriol administration was the treatment of choice to attenuate the progression of secondary hyperparathyroidism (SHPT) and its adverse impact on bone health and vascular calcification. The development of calcitriol analogs, designed to mitigate the resistance to calcitriol suppression of PTH associated with CKD progression, demonstrated survival benefits unrelated to the control of SHPT or skeletal health. The exhaustive search for the pathophysiology behind survival benefits associated with active vitamin D analogs has identified novel anti-inflammatory, anti-hypertensive, anti-aging actions of the vitamin D endocrine system. A major paradigm shift regarding the use of calcitriol or active vitamin D analogs to improve survival in CKD patients emerged upon demonstration of a high prevalence of vitamin D (not calcitriol) deficiency at all stages of CKD and, more significantly, that maintaining serum levels of the calcitriol precursor, 25(OH)vitamin D, above 23 ng/ml delayed CKD progression. The cause of vitamin D deficiency in CKD, however, is unclear since vitamin D bioactivation to 25(OH)D occurs mostly at the liver. Importantly, neither calcitriol nor its analogs can correct vitamin D deficiency. The goals of this chapter are to present our current understanding of the pathogenesis of vitamin D deficiency in CKD and of the causal link between defective vitamin D bioactivation to calcitriol and the onset of molecular pathways that promote CKD progression independently of the degree of SHPT. An understanding of these mechanisms will highlight the need for identification of novel sensitive biomarkers to assess the efficacy of interventions with vitamin D and/or calcitriol(analogs) to ameliorate CKD progression in a PTH-independent manner.
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Affiliation(s)
- Adriana S. Dusso
- Division of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States
| | - Kevin T. Bauerle
- Division of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States
- Department of Medicine, VA Medical Center, St. Louis, MO, United States
| | - Carlos Bernal-Mizrachi
- Division of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States
- Department of Medicine, VA Medical Center, St. Louis, MO, United States
- Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, United States
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15
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Ul Afshan F, Nissar B, Chowdri NA, Ganai BA. Relevance of vitamin D 3 in COVID-19 infection. GENE REPORTS 2021; 24:101270. [PMID: 34250314 PMCID: PMC8260490 DOI: 10.1016/j.genrep.2021.101270] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 05/28/2021] [Accepted: 07/01/2021] [Indexed: 12/15/2022]
Abstract
SARS-CoV-2 virus, the main culprit for COVID-19 disaster, has triggered a gust of curiosity both in the mechanism of action of this infection as well as potential risk factors for disease generation and regimentation. The prime focus of the present review, which is basically a narrative one, is in utilizing the current concepts of vitamin D3 as an agent with myriad functions, one of them being immunocompetence and a promising weapon for both innate and adaptive immunity against COVID-19 infection. Some of the manifestations of SARS-CoV-2 virus such as Acute Respiratory Distress Syndrome (ARDS) overlap with the pathophysiological effects that are overcome due to already established role of vitamin D3 e.g., amelioration of cytokine outburst. Additionally, the cardiovascular complications due to COVID-19 infection may also be connected to vitamin D3 levels and the activity of its active forms. Eventually, we summarise the clinical, observational and epidemiological data of the respiratory diseases including COVID-19 disease and try to bring its association with the potential role of vitamin D3, in particular, the activity of its active forms, circulating levels and its supplementation, against dissemination of this disease.
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Affiliation(s)
- Falaque Ul Afshan
- Department of Biochemistry, University of Kashmir, Hazratbal, Srinagar, J&K 190006, India
| | - Bushra Nissar
- Department of Biochemistry, University of Kashmir, Hazratbal, Srinagar, J&K 190006, India
| | | | - Bashir Ahmad Ganai
- Centre For Research and Development, University of Kashmir, Hazratbal, Srinagar, J&K 190006, India
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16
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Kang NR, Ahn YH, Park E, Lee KH, Baek HS, Kim SH, Cho H, Cho MH, Shin JI, Lee JH, Cheong HI, Kang HG, Park YS, Ha IS, Moon DS, Han KH. Intellectual Functioning of Pediatric Patients with Chronic Kidney Disease: Results from the KNOW-Ped CKD. J Korean Med Sci 2021; 36:e138. [PMID: 34032031 PMCID: PMC8144594 DOI: 10.3346/jkms.2021.36.e138] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Accepted: 04/14/2021] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND Chronic kidney disease (CKD) has a negative impact on growth and development in children and is a risk factor for neurocognitive impairment; however, there is limited research on the cognitive function of children and adolescents with CKD. This study therefore aimed to investigate the mean intelligence and risk factors for low intelligence in children and adolescents with CKD. METHODS Eighty-one patients with CKD under 18 years old were included in the KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease (KNOW-Ped CKD). Participants completed either the Wechsler Intelligence Scale for Children (6-16 years), or Wechsler Adult Intelligence Scale (> 16 years). RESULTS The mean full-scale intelligence quotient (IQ) was 91 ± 19; 24.7% of participants scored a full-scale IQ below 80. Participants with a short stature (height Z scores < -1.88), failure to thrive (weight Z scores < -1.65), more severe CKD stage (≥ IIIb), longer duration of CKD (≥ 5 years), and those who were Medicare or Medicaid beneficiaries, had significantly lower mean full-scale IQs. CONCLUSION On linear regression analysis, the association between the full-scale IQ, and longer duration of CKD and growth failure, remained significant after controlling for demographic and clinical variables. It is therefore necessary to investigate cognitive impairment in pediatric patients with CKD who exhibit growth failure or for a longer postmorbid period. It is believed that early interventions, such as kidney transplantation, will have a positive effect on IQ in children with CKD, as the disease negatively affects IQ due to poor glomerular filtration rate over time. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02165878.
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Affiliation(s)
- Na Ri Kang
- Department of Psychiatry, College of Medicine, Jeju National University, Jeju, Korea
| | - Yo Han Ahn
- Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea
| | - Eujin Park
- Department of Pediatrics, Hallym University Kangnam Sacred Heart Hospital, Seoul, Korea
| | - Keum Hwa Lee
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea
| | - Hee Sun Baek
- Department of Pediatrics, Kyungpook National University, School of Medicine, Daegu, Korea
| | - Seong Heon Kim
- Department of Pediatrics, Pusan National University Children's Hospital, Yangsan, Korea
| | - Heeyeon Cho
- Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Min Hyun Cho
- Department of Pediatrics, Kyungpook National University, School of Medicine, Daegu, Korea
| | - Jae Il Shin
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea
| | - Joo Hoon Lee
- Department of Pediatrics, Asan Medical Center Childrens' Hospital, University of Ulsan College of Medicine, Seoul, Korea
| | - Hae Il Cheong
- Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea
| | - Hee Gyung Kang
- Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea
- Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea
| | - Young Seo Park
- Department of Pediatrics, Asan Medical Center Childrens' Hospital, University of Ulsan College of Medicine, Seoul, Korea
| | - Il Soo Ha
- Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea
- Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea
| | - Duk Soo Moon
- Department of Psychiatry, College of Medicine, Jeju National University, Jeju, Korea
| | - Kyoung Hee Han
- Department of Pediatrics, College of Medicine, Jeju National University, Jeju, Korea.
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17
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dos Santos MS, Canale D, Bernardo DRD, Shimizu MHM, Seguro AC, Volpini RA, de Bragança AC. The Restoration of Vitamin D Levels Slows the Progression of Renal Ischemic Injury in Rats Previously Deficient in Vitamin D. Front Med (Lausanne) 2021; 8:625647. [PMID: 33869246 PMCID: PMC8049292 DOI: 10.3389/fmed.2021.625647] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Accepted: 03/04/2021] [Indexed: 11/13/2022] Open
Abstract
Chronic kidney disease (CKD) remains a global public health problem. The initial damage after ischemia/reperfusion (I/R) injury plays an important role in the pathogenesis of acute kidney injury (AKI) and predisposition to CKD. Several studies have been showing that nontraditional risk factors such as AKI and hypovitaminosis D could also be involved in CKD progression. Vitamin D deficiency (VDD) is associated with hemodynamic changes, activation of inflammatory pathways and renal disease progression (RDP) following I/R-AKI. Strategies for prevention and/or slowing RDP have been determined and the sufficiency of vitamin D has been emerging as a renoprotective factor in many diseases. Therefore, we investigated the effect of the restoration of vitamin D levels in the progression of I/R injury (IRI) in rats previously deficient in vitamin D. On day 30, male Wistar rats were submitted to bilateral 45 min IRI and divided into three groups: IRI, standard diet for 120 days; VDD+IRI, vitamin D-free diet for 120 days; and VDD+IRI+R, vitamin D-free diet in the first 30 days and just after I/R, we reintroduced the standard diet in the last 90 days. After the 120-day protocol, VDD+IRI+R rats presented an improvement in the renal function and renal protein handling followed by a smaller fractional interstitial area. Furthermore, those animals exhibited a reestablishment regarding the hemodynamic parameters and plasma levels of aldosterone, urea and PTH. In addition, the restoration of vitamin D levels reestablished the amount of MCP1 and the renal expressions of CD68+ and CD3+ cells in the VDD+IRI+R rats. Also, VDD+IRI+R rats showed a restoration regarding the amount of collagen type III and renal expressions of fibronectin, vimentin and α-SMA. Such changes were also accompanied by a reestablishment on the renal expression of VDR, Klotho, JG12, and TGF-β1. Our findings indicate that the restoration of vitamin D levels not only improved the renal function and hemodynamics but also reduced the inflammation and fibrosis lesions observed in I/R-AKI associated with VDD. Thus, monitoring of vitamin D status as well as its replacement in the early stages of kidney injury may be a therapeutic alternative in the mitigation of renal disease progression.
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Affiliation(s)
- Michele Santiago dos Santos
- Laboratorio de Investigacao Medica 12 (LIM12), Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Daniele Canale
- Laboratorio de Investigacao Medica 12 (LIM12), Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | | | | | - Antonio Carlos Seguro
- Laboratorio de Investigacao Medica 12 (LIM12), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Rildo Aparecido Volpini
- Laboratorio de Investigacao Medica 12 (LIM12), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Ana Carolina de Bragança
- Laboratorio de Investigacao Medica 12 (LIM12), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
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18
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Makris K, Bhattoa HP, Cavalier E, Phinney K, Sempos CT, Ulmer CZ, Vasikaran SD, Vesper H, Heijboer AC. Recommendations on the measurement and the clinical use of vitamin D metabolites and vitamin D binding protein - A position paper from the IFCC Committee on bone metabolism. Clin Chim Acta 2021; 517:171-197. [PMID: 33713690 DOI: 10.1016/j.cca.2021.03.002] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 01/10/2021] [Accepted: 03/04/2021] [Indexed: 02/08/2023]
Abstract
Vitamin D, an important hormone with a central role in calcium and phosphate homeostasis, is required for bone and muscle development as well as preservation of musculoskeletal function. The most abundant vitamin D metabolite is 25-hydroxyvitamin D [25(OH)D], which is currently considered the best marker to evaluate overall vitamin D status. 25(OH)D is therefore the most commonly measured metabolite in clinical practice. However, several other metabolites, although not broadly measured, are useful in certain clinical situations. Vitamin D and all its metabolites are circulating in blood bound to vitamin D binding protein, (VDBP). This highly polymorphic protein is not only the major transport protein which, along with albumin, binds over 99% of the circulating vitamin D metabolites, but also participates in the transport of the 25(OH)D into the cell via a megalin/cubilin complex. The accurate measurement of 25(OH)D has proved a difficult task. Although a reference method and standardization program are available for 25(OH)D, the other vitamin D metabolites still lack this. Interpretation of results, creation of clinical supplementation, and generation of therapeutic guidelines require not only accurate measurements of vitamin D metabolites, but also the accurate measurements of several other "molecules" related with bone metabolism. IFCC understood this priority and a committee has been established with the task to support and continue the standardization processes of vitamin D metabolites along with other bone-related biomarkers. In this review, we present the position of this IFCC Committee on Bone Metabolism on the latest developments concerning the measurement and standardization of vitamin D metabolites and its binding protein, as well as clinical indications for their measurement and interpretation of the results.
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Affiliation(s)
- Konstantinos Makris
- Clinical Biochemistry Department, KAT General Hospital, 14561 Athens, Greece; Laboratory for Research of the Musculoskeletal System "Th. Garofalidis", Medical School, University of Athens, Athens, Greece.
| | - Harjit P Bhattoa
- Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Etienne Cavalier
- Department of Clinical Chemistry, University of Liège, CHU de Liège, Domaine du Sart-Tilman, B-4000 Liège, Belgium
| | - Karen Phinney
- Biomolecular Measurement Division, National Institute of Standards and Technology, Gaithersburg, MD, USA
| | - Christopher T Sempos
- Coordinator, Vitamin D Standardization Program (VDSP), Havre de Grace, MD 21078, USA
| | - Candice Z Ulmer
- Clinical Chemistry Branch, Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Samuel D Vasikaran
- PathWest Laboratory Medicine, Fiona Stanley Hospital, Murdoch, WA, Australia
| | - Hubert Vesper
- Clinical Chemistry Branch, Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Annemieke C Heijboer
- Department of Clinical Chemistry, Endocrine Laboratory, Amsterdam Gastroenterology Endocrinology & Metabolism, Vrije Universiteit Amsterdam and University of Amsterdam, Amsterdam UMC, Amsterdam, Netherlands
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19
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Tapper M, McGrowder DA, Dilworth L, Soyibo A. Cystatin C, Vitamin D and Thyroid Function Test Profile in Chronic Kidney Disease Patients. Diseases 2021; 9:diseases9010005. [PMID: 33401560 PMCID: PMC7838907 DOI: 10.3390/diseases9010005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Revised: 12/22/2020] [Accepted: 12/27/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND The progression of chronic kidney disease (CKD) is concomitant with complications, including thyroid dysfunction, dyslipidemia and cardiovascular diseases. The aim of this study is to determine serum cystatin C levels, and the prevalence of vitamin D deficiency and thyroid dysfunction in CKD patients. METHODS A cross-sectional study was conducted involving 140 CKD patients (stages 1-5) that were referred to a renal clinic. Demographic data was collected and thyroid function tests, serum 25-OH-vitamin D, cystatin C levels, and routine biochemistry tests were determined using cobas 6000 analyzer. RESULTS 129 (92.1%) of CKD patients had elevated serum cystatin C levels and there was a stepwise increase from stage 1-5. Overt hypothyroidism was present in one patient and nine had subclinical hypothyroidism. There was a stepwise reduction in serum 25-OH-vitamin D levels from stage 2-5, 31 (22.1%) had vitamin D insufficiency and 31 (22.1%) presented with deficiency. CONCLUSIONS 25-OH-vitamin D deficiency and thyroid disorders are exhibited in chronic kidney disease patients and the severity of the former rises with disease progression, as indicated by elevated cystatin C levels. Routine screening and timely intervention is recommended so as to reduce the risk of cardiovascular diseases.
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Affiliation(s)
- Marlene Tapper
- Department of Pathology, Faculty of Medical Sciences, The University of the West Indies, Kingston 7, Jamaica; (M.T.); (L.D.)
| | - Donovan A. McGrowder
- Department of Pathology, Faculty of Medical Sciences, The University of the West Indies, Kingston 7, Jamaica; (M.T.); (L.D.)
- Correspondence:
| | - Lowell Dilworth
- Department of Pathology, Faculty of Medical Sciences, The University of the West Indies, Kingston 7, Jamaica; (M.T.); (L.D.)
| | - Adedamola Soyibo
- Department of Medicine, Faculty of Medical Sciences, The University of the West Indies, Kingston 7, Jamaica;
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20
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Niculescu DA, Deacu LG, Caragheorgheopol A, Popescu N, Ghemigian A, Procopiuc C, Rosca R, Poiana C. Combined Effects of Vitamin D Status, Renal Function and Age on Serum Parathyroid Hormone Levels. Front Endocrinol (Lausanne) 2021; 12:657991. [PMID: 33995282 PMCID: PMC8120293 DOI: 10.3389/fendo.2021.657991] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Accepted: 04/14/2021] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Vitamin D status and renal function are well-known independent predictors of serum parathyroid hormone (PTH) levels. We aimed to describe the combined effects of 25-hydroxy vitamin D (25(OH)D), glomerular filtration rate (GFR) and age on serum PTH levels across the whole clinical spectrum. METHODS We retrieved from our endocrinology center database all PTH measurement between 2012 and 2020 for which a simultaneous measurement of serum 25(OH)D, calcium and creatinine was available. Age, sex and diagnosis were available for all subjects. Intact PTH was measured using the same electrochemiluminescence assay. RESULTS There were 6,444 adults and 701 children without a diagnosis of hyper- or hypoparathyroidism or abnormal serum calcium levels. In adults with 25(OH)D≥12 ng/mL multiple regression models showed that serum PTH was negatively correlated with both 25(OH)D and GFR. Regression (-0.68 and -1.59 vs. -0.45 and -0.22 respectively), partial correlation (-0.16 and -0.35 vs. -0.12 and -0.10 respectively) and determination coefficients (0.14 vs. 0.031) were higher in CKD than in normal renal function. In subjects with 25(OH)D<12 ng/mL, GFR was the only significant predictor in those with CKD (β-coefficient=-2.5, r=-0.55) and 25(OH)D was the only significant predictor in those with normal renal function (β-coefficient=-2.05, r=-0.11). Increasing age was associated with higher PTH levels only in those with normal renal function and 25(OH)D≥12 ng/mL. CONCLUSIONS We showed that declining vitamin D and renal function have additive effects on serum PTH in subjects without vitamin D deficiency. In vitamin D deficient subjects this dependency is stronger but is not additive anymore.
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Affiliation(s)
- Dan Alexandru Niculescu
- Department of Endocrinology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Department of Pituitary and Neuroendocrine Disorders, C. I. Parhon National Institute of Endocrinology, Bucharest, Romania
- *Correspondence: Dan Alexandru Niculescu,
| | - Laura Georgiana Deacu
- Department of Pituitary and Neuroendocrine Disorders, C. I. Parhon National Institute of Endocrinology, Bucharest, Romania
| | - Andra Caragheorgheopol
- Research Laboratory, C. I. Parhon National Institute of Endocrinology, Bucharest, Romania
| | - Nicoleta Popescu
- Biochemistry Department, C. I. Parhon National Institute of Endocrinology, Bucharest, Romania
| | - Adina Ghemigian
- Department of Gonadal Disorders, C. I. Parhon National Institute of Endocrinology, Bucharest, Romania
| | - Camelia Procopiuc
- Department of Pediatric Endocrinology, C. I. Parhon National Institute of Endocrinology, Bucharest, Romania
| | - Roxana Rosca
- Department of Adrenal and Bone Disorders, C. I. Parhon National Institute of Endocrinology, Bucharest, Romania
| | - Catalina Poiana
- Department of Endocrinology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Department of Pituitary and Neuroendocrine Disorders, C. I. Parhon National Institute of Endocrinology, Bucharest, Romania
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21
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Vitamin D and sleep duration: Is there a bidirectional relationship? Horm Mol Biol Clin Investig 2020; 41:/j/hmbci.ahead-of-print/hmbci-2020-0025/hmbci-2020-0025.xml. [DOI: 10.1515/hmbci-2020-0025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2020] [Accepted: 10/26/2020] [Indexed: 11/15/2022]
Abstract
Abstract
Vitamin D contributes to numerous physiological processes within the body but primarily calcium and bone homeostasis. Emerging evidence highlights a novel role for vitamin D in maintaining and regulating optimal sleep. Sleep is a known regulator of bone health, highlighting the interconnectedness between vitamin D concentrations, sleep duration and bone metabolism. It is possible that the relationship between sleep length and vitamin D is bidirectional, with vitamin D playing a role in sleep health and conversely, sleep affecting vitamin D levels. Nevertheless, limited information on the direction of the interaction is available, and much remains to be learned concerning the complex relationship between insufficient sleep duration and vitamin D deficiency. Given the potential to implement interventions to improve sleep and vitamin D supplementation, understanding this relationship further could represent a novel way to support and improve health.
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22
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Zafalon RVA, Ruberti B, Rentas MF, Amaral AR, Vendramini THA, Chacar FC, Kogika MM, Brunetto MA. The Role of Vitamin D in Small Animal Bone Metabolism. Metabolites 2020; 10:E496. [PMID: 33287408 PMCID: PMC7761812 DOI: 10.3390/metabo10120496] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 11/09/2020] [Accepted: 11/10/2020] [Indexed: 12/14/2022] Open
Abstract
Dogs and cats have differences in vitamin D metabolism compared to other mammalian species, as they are unable to perform vitamin D cutaneous synthesis through sun exposure. Therefore, they are dependent on the dietary intake of this nutrient. The classic functions of vitamin D are to stimulate intestinal calcium and phosphate absorption, renal calcium and phosphate reabsorption and regulate bone mineral metabolism. Thus, it is an important nutrient for calcium and phosphorus homeostasis. This review highlights the evidence of the direct and indirect actions of vitamin D on bone mineral metabolism, the consequences of nutritional imbalances of this nutrient in small animals, as well as differences in vitamin D metabolism between different size dogs.
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Affiliation(s)
- Rafael Vessecchi Amorim Zafalon
- Pet Nutrology Research Center, Nutrition and Production Department, School of Veterinary Medicine and Animal Science, University of São Paulo, Jardim Elite, Pirassununga 13635-900, Brazil; (R.V.A.Z.); (M.F.R.); (T.H.A.V.)
| | - Bruna Ruberti
- Small Animal Internal Medicine Service, Veterinary Teaching Hospital, School of Veterinary Medicine and Animal Science, University of São Paulo, Cidade Universitária, São Paulo 05508-270, Brazil; (B.R.); (M.M.K.)
| | - Mariana Fragoso Rentas
- Pet Nutrology Research Center, Nutrition and Production Department, School of Veterinary Medicine and Animal Science, University of São Paulo, Jardim Elite, Pirassununga 13635-900, Brazil; (R.V.A.Z.); (M.F.R.); (T.H.A.V.)
| | - Andressa Rodrigues Amaral
- Veterinary Nutrology Service, Veterinary Teaching Hospital, School of Veterinary Medicine and Animal Science, University of São Paulo, Cidade Universitária, São Paulo 05508-270, Brazil;
| | - Thiago Henrique Annibale Vendramini
- Pet Nutrology Research Center, Nutrition and Production Department, School of Veterinary Medicine and Animal Science, University of São Paulo, Jardim Elite, Pirassununga 13635-900, Brazil; (R.V.A.Z.); (M.F.R.); (T.H.A.V.)
| | - Fernanda Chicharo Chacar
- Department of Internal Medicine, Federal Institute of Education, Science and Technology of South of Minas Gerais, IFSULDEMINAS, Muzambinho 37890-000, Brazil;
| | - Marcia Mery Kogika
- Small Animal Internal Medicine Service, Veterinary Teaching Hospital, School of Veterinary Medicine and Animal Science, University of São Paulo, Cidade Universitária, São Paulo 05508-270, Brazil; (B.R.); (M.M.K.)
| | - Marcio Antonio Brunetto
- Pet Nutrology Research Center, Nutrition and Production Department, School of Veterinary Medicine and Animal Science, University of São Paulo, Jardim Elite, Pirassununga 13635-900, Brazil; (R.V.A.Z.); (M.F.R.); (T.H.A.V.)
- Veterinary Nutrology Service, Veterinary Teaching Hospital, School of Veterinary Medicine and Animal Science, University of São Paulo, Cidade Universitária, São Paulo 05508-270, Brazil;
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23
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Bilezikian JP, Bikle D, Hewison M, Lazaretti-Castro M, Formenti AM, Gupta A, Madhavan MV, Nair N, Babalyan V, Hutchings N, Napoli N, Accili D, Binkley N, Landry DW, Giustina A. MECHANISMS IN ENDOCRINOLOGY: Vitamin D and COVID-19. Eur J Endocrinol 2020; 183:R133-R147. [PMID: 32755992 PMCID: PMC9494342 DOI: 10.1530/eje-20-0665] [Citation(s) in RCA: 256] [Impact Index Per Article: 51.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 07/27/2020] [Accepted: 08/04/2020] [Indexed: 12/18/2022]
Abstract
The SARS-CoV-2 virus responsible for the COVID-19 pandemic has generated an explosion of interest both in the mechanisms of infection leading to dissemination and expression of this disease, and in potential risk factors that may have a mechanistic basis for disease propagation or control. Vitamin D has emerged as a factor that may be involved in these two areas. The focus of this article is to apply our current understanding of vitamin D as a facilitator of immunocompetence both with regard to innate and adaptive immunity and to consider how this may relate to COVID-19 disease. There are also intriguing potential links to vitamin D as a factor in the cytokine storm that portends some of the most serious consequences of SARS-CoV-2 infection, such as the acute respiratory distress syndrome. Moreover, cardiac and coagulopathic features of COVID-19 disease deserve attention as they may also be related to vitamin D. Finally, we review the current clinical data associating vitamin D with SARS-CoV-2 infection, a putative clinical link that at this time must still be considered hypothetical.
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Affiliation(s)
- John P Bilezikian
- Endocrinology Division, Department of Medicine, New York-Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, USA
| | - Daniel Bikle
- Endocrine Unit, Veterans Affairs Medical Center, University of California, San Francisco, California, USA
| | - Martin Hewison
- Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
| | - Marise Lazaretti-Castro
- Division of Endocrinology, Escola Paulista de Medicina – Universidade Federal de Sao Paulo (EPM-UNIFESP), Sao Paulo, Brazil
| | - Anna Maria Formenti
- Institute of Endocrine and Metabolic Sciences, San Raffaele, Vita-Salute University and IRCCS Hospital, Milano, Italy
| | - Aakriti Gupta
- Division of Cardiology, Department of Medicine, NewYork-Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, USA
- Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, USA
- Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, Connecticut, USA
| | - Mahesh V Madhavan
- Division of Cardiology, Department of Medicine, NewYork-Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, USA
- Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, USA
| | - Nandini Nair
- Endocrinology Division, Department of Medicine, New York-Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, USA
| | | | | | - Nicola Napoli
- Unit of Endocrinology and Diabetes, Campus Bio-Medico University of Rome, Rome, Italy
- Division of Bone and Mineral Diseases, Washington University in St Louis, St Louis, Missouri, USA
| | - Domenico Accili
- Endocrinology Division, Department of Medicine, New York-Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, USA
| | - Neil Binkley
- University of Wisconsin, Madison, Wisconsin, USA
| | - Donald W Landry
- Division of Nephrology, Department of Medicine, NewYork-Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, USA
| | - Andrea Giustina
- Institute of Endocrine and Metabolic Sciences, San Raffaele, Vita-Salute University and IRCCS Hospital, Milano, Italy
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24
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Podkowińska A, Formanowicz D. Chronic Kidney Disease as Oxidative Stress- and Inflammatory-Mediated Cardiovascular Disease. Antioxidants (Basel) 2020; 9:E752. [PMID: 32823917 PMCID: PMC7463588 DOI: 10.3390/antiox9080752] [Citation(s) in RCA: 163] [Impact Index Per Article: 32.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 08/08/2020] [Accepted: 08/10/2020] [Indexed: 12/12/2022] Open
Abstract
Generating reactive oxygen species (ROS) is necessary for both physiology and pathology. An imbalance between endogenous oxidants and antioxidants causes oxidative stress, contributing to vascular dysfunction. The ROS-induced activation of transcription factors and proinflammatory genes increases inflammation. This phenomenon is of crucial importance in patients with chronic kidney disease (CKD), because atherosclerosis is one of the critical factors of their cardiovascular disease (CVD) and increased mortality. The effect of ROS disrupts the excretory function of each section of the nephron. It prevents the maintenance of intra-systemic homeostasis and leads to the accumulation of metabolic products. Renal regulatory mechanisms, such as tubular glomerular feedback, myogenic reflex in the supplying arteriole, and the renin-angiotensin-aldosterone system, are also affected. It makes it impossible for the kidney to compensate for water-electrolyte and acid-base disturbances, which progress further in the mechanism of positive feedback, leading to a further intensification of oxidative stress. As a result, the progression of CKD is observed, with a spectrum of complications such as malnutrition, calcium phosphate abnormalities, atherosclerosis, and anemia. This review aimed to show the role of oxidative stress and inflammation in renal impairment, with a particular emphasis on its influence on the most common disturbances that accompany CKD.
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Affiliation(s)
| | - Dorota Formanowicz
- Department of Clinical Biochemistry and Laboratory Medicine, Poznan University of Medical Sciences, Rokietnicka 8, 60-806 Poznan, Poland
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Tizhe EV, Ibrahim NDG, Fatihu MY, Ambali SF, Igbokwe IO, Tizhe UD. Effect of zinc supplementation on chronic hepatorenal toxicity following oral exposure to glyphosate-based herbicide (Bushfire®) in rats. J Int Med Res 2020; 48:300060520925343. [PMID: 32865084 PMCID: PMC7469744 DOI: 10.1177/0300060520925343] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2020] [Accepted: 04/17/2020] [Indexed: 11/17/2022] Open
Abstract
OBJECTIVES To assess the effects of zinc pretreatment on hepatorenal toxicity following chronic exposure to glyphosate-based herbicides in male rats. METHODS Following zinc pretreatment (50 mg/kg and 100 mg/kg), 14.4 to 750 mg/kg of oral glyphosate (Bushfire® herbicide) was administered daily for 36 weeks. Thereafter, serum samples were obtained following jugular venipuncture. Liver and kidney samples were processed for histopathological examination. RESULTS Serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase activity as well as levels of bicarbonate, calcium, creatinine were significantly increased following chronic exposure to Bushfire®. Serum levels of sodium, potassium, chloride, total protein, albumin, globulin and urea were unchanged. Moderate to severe coagulative necrosis of hepatocytes as well as glomerular and renal tubular necrosis were observed in herbicide-treated rats. Zinc pretreatment reduced the elevation of serum enzymes associated with hepatobiliary lesions, abrogated hypercalcemia and metabolic alkalosis, and mitigated serum accumulation of creatinine following Bushfire® exposure, but was ineffective in completely preventing histological lesions. CONCLUSION Chronic Bushfire® exposure in rats caused hepatorenal toxicity. The effects of exposure on serum parameters were ameliorated by zinc pretreatment, but the histopathological changes associated with toxicity persisted in milder forms in zinc-pretreated animals.
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Affiliation(s)
- Emmanuel Vandi Tizhe
- Department of Veterinary Microbiology and Pathology, Faculty of Veterinary Medicine, University of Jos, Jos, Plateau State, Nigeria
| | - Najume Dogon-Giginya Ibrahim
- Department of Veterinary Pathology, Faculty of Veterinary Medicine, Ahmadu Bello University, Zaria, Kaduna State, Nigeria
| | - Mohammed Yakasai Fatihu
- Department of Veterinary Pathology, Faculty of Veterinary Medicine, Ahmadu Bello University, Zaria, Kaduna State, Nigeria
| | - Suleiman Folorunsho Ambali
- Department of Veterinary Physiology and Pharmacology, Faculty of Veterinary Medicine, University of Ilorin, Ilorin, Kwara State, Nigeria
| | - Ikechukwu Onyebuchi Igbokwe
- Department of Veterinary Pathology, Faculty of Veterinary Medicine, University of Maiduguri, Maiduguri, Borno State, Nigeria
| | - Ussa Delia Tizhe
- Department of Veterinary Medicine, Faculty of Veterinary Medicine, Ahmadu Bello University, Zaria, Kaduna State, Nigeria
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Imafuku T, Watanabe H, Satoh T, Matsuzaka T, Inazumi T, Kato H, Tanaka S, Nakamura Y, Nakano T, Tokumaru K, Maeda H, Mukunoki A, Takeo T, Nakagata N, Tanaka M, Matsushita K, Tsuchiya S, Sugimoto Y, Shimano H, Fukagawa M, Maruyama T. Advanced Oxidation Protein Products Contribute to Renal Tubulopathy via Perturbation of Renal Fatty Acids. ACTA ACUST UNITED AC 2020; 1:781-796. [DOI: 10.34067/kid.0000772019] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Accepted: 06/01/2020] [Indexed: 11/27/2022]
Abstract
BackgroundRenal proximal tubulopathy plays a crucial role in kidney disease, but its molecular mechanism is incompletely understood. Because proximal tubular cells consume a lot of energy during reabsorption, the relationship between fatty acids (FAs) and proximal tubulopathy has been attracting attention. The purpose of this study is to investigate the association between change in renal FA composition and tubulopathy.MethodsMice with cisplatin-induced nephrotoxicity were used as a model of AKI and 5/6-nephrectomized mice were used as a model of CKD. Renal FA composition in mice was measured by GC-MS. Human tubular epithelial cells (HK-2 cells) were used for in vitro studies.ResultsIn kidneys of AKI mice, increased stearic acid (C18:0) and decreased palmitic acid (C16:0) were observed, accompanied by increased expression of the long-chain FA elongase Elovl6. Similar results were also obtained in CKD mice. We show that C18:0 has higher tubular toxicity than C16:0 via induction of ER stress. Using adenovirus-expressing Elovl6 or siRNA for Elovl6 in HK-2 cells, we demonstrated that increased Elovl6 expression contributes to tubulopathy via increasing C18:0. Elovl6 knockout suppressed the increased serum creatinine levels, renal ER stress, and inflammation that would usually result after 5/6 nephrectomy. Advanced oxidation protein products (AOPPs), specifically an oxidized albumin, was found to induce Elovl6 via the mTORC1/SREBP1 pathway.ConclusionsAOPPs may contribute to renal tubulopathy via perturbation of renal FAs through induction of Elovl6. The perturbation of renal FAs induced by the AOPPs-Elovl6 system could be a potential target for the treatment of tubulopathy.
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27
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Makris K, Sempos C, Cavalier E. The measurement of vitamin D metabolites: part I-metabolism of vitamin D and the measurement of 25-hydroxyvitamin D. Hormones (Athens) 2020; 19:81-96. [PMID: 31919677 DOI: 10.1007/s42000-019-00169-7] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Accepted: 12/16/2019] [Indexed: 12/14/2022]
Abstract
It has been more than 80 years since the discovery of vitamin D and its ability to cure rickets in children. Vitamin D is a secosteroid and comes in two distinct forms, vitamin D2 and vitamin D3. During the last 40 years, the synthesis and metabolism of vitamin D were elucidated and more than 50 metabolites of vitamin D have been discovered, though commercial measurement procedures have been developed for only a few of them. The clinical significance of vitamin D in calcium and phosphorus homeostasis is well appreciated. However, recent epidemiological data have indicated that it has several extra-skeletal physiologic actions which are still a matter of scientific debate. Both research findings and the debate around the interpretation of the research results have created increased interest in more measurements of vitamin D. With the ever growing family of measurable vitamin D metabolites and the measuring techniques comes a question: What metabolic product will provide the right answers and which is the best way to measure it. The right choice of analytical technique is connected with the question of which metabolite we aim to measure, what is its serum concentration, and the purpose of the measurement. The aim of the first part of this review is to provide a brief overview of vitamin D metabolism and a more detailed analysis of the existing methods and the status of standardization for the measurement of 25-hydroxyvitamin D.
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Affiliation(s)
- Konstantinos Makris
- Clinical Biochemistry Department, KAT General Hospital, Kifissia, Athens, Greece.
| | - Christopher Sempos
- Vitamin D Standardization Program (VDSP), Havre de Grace, MD, 21078, USA
| | - Etienne Cavalier
- Department of Clinical Chemistry, University of Liege, CHU de Liege, Liege, Belgium
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28
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Hou YC, Lu CL, Zheng CM, Liu WC, Yen TH, Chen RM, Lin YF, Chao CT, Lu KC. The Role of Vitamin D in Modulating Mesenchymal Stem Cells and Endothelial Progenitor Cells for Vascular Calcification. Int J Mol Sci 2020; 21:2466. [PMID: 32252330 PMCID: PMC7177675 DOI: 10.3390/ijms21072466] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Revised: 03/26/2020] [Accepted: 03/30/2020] [Indexed: 12/12/2022] Open
Abstract
Vascular calcification, which involves the deposition of calcifying particles within the arterial wall, is mediated by atherosclerosis, vascular smooth muscle cell osteoblastic changes, adventitial mesenchymal stem cell osteoblastic differentiation, and insufficiency of the calcification inhibitors. Recent observations implied a role for mesenchymal stem cells and endothelial progenitor cells in vascular calcification. Mesenchymal stem cells reside in the bone marrow and the adventitial layer of arteries. Endothelial progenitor cells that originate from the bone marrow are an important mechanism for repairing injured endothelial cells. Mesenchymal stem cells may differentiate osteogenically by inflammation or by specific stimuli, which can activate calcification. However, the bioactive substances secreted from mesenchymal stem cells have been shown to mitigate vascular calcification by suppressing inflammation, bone morphogenetic protein 2, and the Wingless-INT signal. Vitamin D deficiency may contribute to vascular calcification. Vitamin D supplement has been used to modulate the osteoblastic differentiation of mesenchymal stem cells and to lessen vascular injury by stimulating adhesion and migration of endothelial progenitor cells. This narrative review clarifies the role of mesenchymal stem cells and the possible role of vitamin D in the mechanisms of vascular calcification.
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Affiliation(s)
- Yi-Chou Hou
- Division of Nephrology, Department of Medicine, Cardinal-Tien Hospital, New Taipei City 231, Taiwan;
- School of Medicine, Fu-Jen Catholic University, New Taipei City 234, Taiwan;
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; (C.-M.Z.); (W.-C.L.); (Y.-F.L.)
| | - Chien-Lin Lu
- School of Medicine, Fu-Jen Catholic University, New Taipei City 234, Taiwan;
- Division of Nephrology, Department of Medicine, Fu-Jen Catholic University Hospital, New Taipei City 243, Taiwan
| | - Cai-Mei Zheng
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; (C.-M.Z.); (W.-C.L.); (Y.-F.L.)
- Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
- Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei 235, Taiwan
| | - Wen-Chih Liu
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; (C.-M.Z.); (W.-C.L.); (Y.-F.L.)
- Division of Nephrology, Department of Internal Medicine, Tungs’ Taichung Metroharbor Hospital, Taichung City 43304, Taiwan
| | - Tzung-Hai Yen
- Department of Nephrology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan;
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Ruei-Ming Chen
- Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan;
| | - Yuh-Feng Lin
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; (C.-M.Z.); (W.-C.L.); (Y.-F.L.)
- Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
- Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei 235, Taiwan
| | - Chia-Ter Chao
- Graduate Institute of Toxicology, National Taiwan University College of Medicine, Taipei 104, Taiwan
- Nephrology division, Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital BeiHu Branch, Taipei 108, Taiwan
| | - Kuo-Cheng Lu
- School of Medicine, Fu-Jen Catholic University, New Taipei City 234, Taiwan;
- Division of Nephrology, Department of Medicine, Fu-Jen Catholic University Hospital, New Taipei City 243, Taiwan
- Division of Nephrology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, and School of Medicine, Buddhist Tzu Chi University, Hualien, Taiwan
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Giustina A, Adler RA, Binkley N, Bollerslev J, Bouillon R, Dawson-Hughes B, Ebeling PR, Feldman D, Formenti AM, Lazaretti-Castro M, Marcocci C, Rizzoli R, Sempos CT, Bilezikian JP. Consensus statement from 2 nd International Conference on Controversies in Vitamin D. Rev Endocr Metab Disord 2020; 21:89-116. [PMID: 32180081 PMCID: PMC7113202 DOI: 10.1007/s11154-019-09532-w] [Citation(s) in RCA: 173] [Impact Index Per Article: 34.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The 2nd International Conference on Controversies in Vitamin D was held in Monteriggioni (Siena), Italy, September 11-14, 2018. The aim of this meeting was to address ongoing controversies and timely topics in vitamin D research, to review available data related to these topics and controversies, to promote discussion to help resolve lingering issues and ultimately to suggest a research agenda to clarify areas of uncertainty. Several issues from the first conference, held in 2017, were revisited, such as assays used to determine serum 25-hydroxyvitamin D [25(OH)D] concentration, which remains a critical and controversial issue for defining vitamin D status. Definitions of vitamin D nutritional status (i.e. sufficiency, insufficiency and deficiency) were also revisited. New areas were reviewed, including vitamin D threshold values and how they should be defined in the context of specific diseases, sources of vitamin D and risk factors associated with vitamin D deficiency. Non-skeletal aspects related to vitamin D were also discussed, including the reproductive system, neurology, chronic kidney disease and falls. The therapeutic role of vitamin D and findings from recent clinical trials were also addressed. The topics were considered by 3 focus groups and divided into three main areas: 1) "Laboratory": assays and threshold values to define vitamin D status; 2) "Clinical": sources of vitamin D and risk factors and role of vitamin D in non-skeletal disease and 3) "Therapeutics": controversial issues on observational studies and recent randomized controlled trials. In this report, we present a summary of our findings.
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Affiliation(s)
- A Giustina
- Chair of Endocrinology, School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
- Division of Endocrinology, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - R A Adler
- McGuire Veterans Affairs Medical Center and Virginia Commonwealth University School of Medicine, Richmond, VA, USA
| | - N Binkley
- Osteoporosis Clinical Research Program and Institute on Aging, University of Wisconsin-Madison, Madison, WI, USA
| | - J Bollerslev
- Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- Faculty of Medicine, University of Oslo, Oslo, Norway
| | - R Bouillon
- Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases, Metabolism and Ageing, Leuven, KU, Belgium
| | - B Dawson-Hughes
- Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA
| | - P R Ebeling
- Department of Medicine, School of Clinical Sciences, Monash University, Clayton, VIC, Australia
| | - D Feldman
- Department of Medicine, Endocrinology Division, Stanford University School of Medicine, Stanford, CA, USA
| | - A M Formenti
- Chair of Endocrinology, School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
- Division of Endocrinology, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - M Lazaretti-Castro
- Division of Endocrinology, Escola Paulista de Medicina - Universidade Federal de Sao Paulo (EPM-UNIFESP), Sao Paulo, Brazil
| | - C Marcocci
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - R Rizzoli
- Divison of Bone Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland
| | - C T Sempos
- Vitamin D Standardization Program LLC, Havre de Grace, MD, USA
| | - J P Bilezikian
- Department of Medicine, Endocrinology Division, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
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Kaur G, Singh J, Kumar J. Vitamin D and cardiovascular disease in chronic kidney disease. Pediatr Nephrol 2019; 34:2509-2522. [PMID: 30374603 PMCID: PMC6488464 DOI: 10.1007/s00467-018-4088-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Revised: 09/09/2018] [Accepted: 09/13/2018] [Indexed: 12/31/2022]
Abstract
Chronic kidney disease (CKD) is considered an independent risk factor for cardiovascular disease, with increased cardiovascular morbidity and mortality seen even in the early stages of CKD. Several studies have shown a high prevalence of vitamin D deficiency in individuals with CKD. Low vitamin D levels upregulate the renin-angiotensin-aldosterone system (RAAS), cause endothelial dysfunction, and increase inflammation. Epidemiological studies show an association between vitamin D deficiency and risk factors for cardiovascular disease, but a causal relationship has not been established. The high cardiovascular morbidity and mortality associated with CKD in adults requires therapies to decrease this elevated risk. However, results from several meta-analyses and randomized clinical trials in adults have not shown convincing evidence for the use of vitamin D therapy in improving cardiovascular outcomes. Lack of high-quality evidence from randomized clinical trials in children regarding the effectiveness and long-term safety of vitamin D treatment precludes any recommendations on its use to mitigate the cardiovascular burden of CKD.
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Affiliation(s)
- Gurpreet Kaur
- State University of New York Downstate Medical Center
| | | | - Juhi Kumar
- New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY, USA.
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Lee SM, Lee MH, Son YK, Kim SE, An WS. Combined Treatment with Omega-3 Fatty Acid and Cholecalciferol Increases 1,25-Dihydroxyvitamin D Levels by Modulating Dysregulation of Vitamin D Metabolism in 5/6 Nephrectomy Rats. Nutrients 2019; 11:nu11122903. [PMID: 31805709 PMCID: PMC6950759 DOI: 10.3390/nu11122903] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Revised: 11/25/2019] [Accepted: 11/26/2019] [Indexed: 12/19/2022] Open
Abstract
The protein 1α-hydroxylase (CYP27B1) was expressed in liver and omega-3 fatty acid (FA) elevated 1,25-dihydroxyvitamin D [1,25(OH)2D] levels in dialysis patients. The aim of this study was to determine whether omega-3 FA and cholecalciferol have effects on vitamin D metabolism related to CYP27B1 and 24-hydroxylase (CYP24) activities in the kidney and liver of 5/6 nephrectomy (Nx) rats. Male Sprague–Dawley rats were divided into the following groups: sham control, 5/6 Nx, 5/6 Nx treated with cholecalciferol, 5/6 Nx treated with omega-3 FA, and 5/6 Nx treated with cholecalciferol/omega-3 FA. CYP27B1 and CYP24 expression were measured in the liver and kidney. Further, 1,25(OH)2D and 25-hydroxyvitamin D [25(OH)D] levels were measured in serum. Among Nx groups, 1,25(OH)2D and 25(OH)D levels were lowest in the 5/6 Nx group. CYP24 expression was increased in the kidney of the 5/6 Nx rat model, which was found to be reversed by omega-3 FA or cholecalciferol/omega-3 FA supplementation. Decreased CYP27B1 expression was observed in the liver of the 5/6 Nx rats and its expression was recovered by supplementation with cholecalciferol/omega-3 FA. In conclusion, omega-3 FA and cholecalciferol may synergistically increase 1,25(OH)2D levels by inhibiting CYP24 expression in the kidney and liver and activating CYP27B1 expression in the liver of 5/6 Nx rats.
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Affiliation(s)
- Su Mi Lee
- Department of Internal Medicine, Dong-A University, Busan 49201, Korea; (S.M.L.); (Y.K.S.); (S.E.K.)
| | - Mi Hwa Lee
- Department of Anatomy and Cell Biology and Mitochondria Hub Regulation Center, Dong-A University, Busan 49201, Korea;
| | - Young Ki Son
- Department of Internal Medicine, Dong-A University, Busan 49201, Korea; (S.M.L.); (Y.K.S.); (S.E.K.)
| | - Seong Eun Kim
- Department of Internal Medicine, Dong-A University, Busan 49201, Korea; (S.M.L.); (Y.K.S.); (S.E.K.)
| | - Won Suk An
- Department of Internal Medicine, Dong-A University, Busan 49201, Korea; (S.M.L.); (Y.K.S.); (S.E.K.)
- Correspondence: ; Tel.: +82-51-240-2811; Fax: +82-51-242-5852
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Severe Hypocalcemia and Resulting Seizure Caused by Vitamin D Deficiency in an Older Patient Receiving Phenytoin: Eldecalcitol and Maxacalcitol Ointment as Potential Therapeutic Options for Hypocalcemia. Case Rep Nephrol 2019; 2019:3653276. [PMID: 31737385 PMCID: PMC6815596 DOI: 10.1155/2019/3653276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Revised: 07/26/2019] [Accepted: 08/07/2019] [Indexed: 11/17/2022] Open
Abstract
An 82-year-old man treated with phenytoin for the prevention of symptomatic epilepsy was hospitalized to treat consciousness disturbance, seizure, and hypocalcemia (serum calcium: 4.6 mg/dL). Serum 25-hydroxyvitamin D level was very low (5.4 ng/mL), whereas serum calcitriol level was normal (27 pg/mL) and serum intact parathyroid hormone level was increased (369 pg/mL). He was finally diagnosed with vitamin D deficiency associated with low sunlight exposure and long-term phenytoin use for symptomatic epilepsy: phenytoin is shown to accelerate catabolism of 25-hydroxyvitamin D. Combination treatment with eldecalcitol and maxacalcitol ointments successfully normalized corrected serum calcium level: both eldecalcitol and maxacalcitol are vitamin D receptor activators used for osteoporosis and psoriasis, respectively. Our case illustrates the importance of periodic serum calcium level monitoring in patients receiving anti-epileptic drugs and the usefulness of eldecalcitol and maxacalcitol ointment as a therapeutic option for hypocalcemia, especially in countries where native vitamin D and 25-hydroxyvitamin D are not available.
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Hu C, Wu X. Effect of Vitamin D Supplementation on Vascular Function and Inflammation in Patients with Chronic Kidney Disease: A Controversial Issue. Ther Apher Dial 2019; 24:265-274. [PMID: 31400089 DOI: 10.1111/1744-9987.13428] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2019] [Revised: 08/06/2019] [Accepted: 08/08/2019] [Indexed: 12/22/2022]
Abstract
Vitamin D deficiency is common in patients with CKD and is associated with vascular dysfunction and inflammation. In recent years, some randomized controlled trials have revealed the effect of vitamin D supplementation on vascular function and inflammation in CKD patients, but the results are inconsistent. Thus, in light of the controversy, we performed a systematic review and meta-analysis of the effect of vitamin D in patients with CKD. We searched the literature in multiple databases for clinical trials from the date of inception to December 2018. The standardized mean difference (SMD) effect size was pooled using fixed and random effects models. A total of 10 randomized controlled trials involving 579 patients were included in the meta-analysis; among these, 313 patients were treated with vitamin D, and the control group included 266 who received a placebo. This meta-analysis revealed no statistical significance in the levels of flow-mediated dilatation (SMD, 0.94; 95% CI, -0.33 to 2.21; P = 0.15); pulse wave velocity (SMD, -0.13; 95% CI, -0.38 to 0.13; P = 0.33); systolic BP (SMD, -0.04; 95% CI, -0.29 to 0.22; P = 0.77); diastolic BP (SMD, 0.01; 95% CI, -0.26 to 0.27; P = 0.97); and CRP (SMD, -0.09; 95% CI, -0.44 to 0.26; P = 0.61) between the vitamin D group and controls for patients with CKD. Short-term intervention with vitamin D was not associated with improvements in vascular function and inflammation, as measured by flow-mediated dilatation, pulse wave velocity, systolic BP, diastolic BP and CRP. This suggested that there is insufficient evidence to conclude the benefit of vitamin D supplementation on vascular function and inflammation in CKD patients.
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Affiliation(s)
- Chun Hu
- Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Xiaoyan Wu
- Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan, China
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Vitamin D Metabolic Ratio and Risks of Death and CKD Progression. Kidney Int Rep 2019; 4:1598-1607. [PMID: 31891001 PMCID: PMC6933450 DOI: 10.1016/j.ekir.2019.08.014] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Revised: 08/15/2019] [Accepted: 08/19/2019] [Indexed: 12/28/2022] Open
Abstract
Introduction Assessment of impaired vitamin D metabolism is limited by lack of functional measures. CYP24A1-mediated vitamin D clearance, calculated as the ratio of serum 24,25-dihydroxyvitamin D3 to 25-hydroxyvitamin D3 (the vitamin D metabolic ratio, VDMR), is induced by 1,25-dihydroxyvitamin D and may assess tissue-level activity. We tested associations of the VDMR with risks of death and progression to end-stage renal disease (ESRD) in patients with chronic kidney disease (CKD). Methods We studied participants from the Chronic Renal Insufficiency Cohort (CRIC), which included a random subset of 1080 CRIC participants plus additional participants who experienced ESRD or died (case cohort study design). Serum 24,25-dihydroxyvitamin D3 and 25-hydroxyvitamin D3 was measured 1 year after enrollment. The primary outcomes included death and progression to ESRD. Using inverse probability weighting, we tested associations of VDMR (24,25[OH]2D3/25[OH]D3) with risks of death and ESRD, adjusting for demographics, comorbidity, and kidney function (estimated glomerular filtration rate [eGFR] and urine protein-to-creatinine ratio [PCR]). Results There were a total of 708 ESRD events and 650 deaths events over mean (SD) follow-up periods of 4.9 (2.9) years and 6.5 (2.5) years, respectively. Lower VDMR was associated with increased risk of ESRD prior to adjusting for kidney function (hazard ratio [HR], 1.80 per 20 pg/ng lower VDMR; 95% confidence interval [CI], 1.56–2.08), but not with adjustment for kidney function (HR, 0.94 per 20 pg/ng; 95% CI, 0.81–1.10). Lower VDMR was associated with modestly increased mortality risk, including adjustment for kidney function (HR, 1.18 per 20 pg/ng; 95% CI, 1.02–1.36). Conclusion Lower VDMR, a measure of CYP24A1-mediated vitamin D clearance, was significantly associated with all-cause mortality but not with progression to ESRD in patients with CKD.
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Kleine CE, Obi Y, Streja E, Hsiung JT, Park C, Holick MF, Kalantar-Zadeh K. Seasonal variation of serum 25-hydroxyvitamin D and parameters of bone and mineral disorder in dialysis patients. Bone 2019; 124:158-165. [PMID: 30858148 DOI: 10.1016/j.bone.2019.03.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2018] [Revised: 02/20/2019] [Accepted: 03/04/2019] [Indexed: 12/18/2022]
Abstract
BACKGROUND Vitamin D deficiency is common among dialysis patients and may impact blood concentrations of calcium, phosphorus, intact parathyroid hormone (iPTH), and alkaline phosphatase (ALP). Seasonal variation of serum 25-hydroxyvitamin D [25(OH)D] concentrations has been well established for the general population; however, less is known about circannual variation in 25(OH)D as well as other parameters of mineral and bone disorder among dialysis patients. METHOD Based on 57,500 serum 25(OH)D measurements collected over two years from January 2009 to December 2010 among 25,025 dialysis patients, we evaluated the circannual variations in serum concentrations of 25(OH)D, calcium, phosphorus, iPTH, and ALP by a linear regression model with a cosinor function for the time period (month). We adjusted for potential confounders including case-mix variables, and ultraviolet index. RESULTS Serum 25(OH)D concentrations showed significant circannual variation and mean serum 25(OH)D was 3.2 ng/mL higher in summer than in winter. Furthermore, 25(OH)D concentration increased steadily by 1.3 ng/mL per year. While serum calcium concentrations showed statistically significant but clinically negligible seasonal variation (0.02 mg/dL in peak-trough difference), serum phosphorus did not follow such a pattern. Serum iPTH concentrations also showed a modest seasonal variation with 9% higher values in winter than in summer. Concordantly, ALP concentrations in the winter were 2% higher than in the summer time. Seasonal variation of 25(OH)D was greater in male (vs. female), African-American (vs. non-African-American), and younger (vs. older) dialysis patients. CONCLUSION Serum 25(OH)D and iPTH concentrations show seasonal variation among dialysis patients while the variation in other parameters of mineral and bone disorder was clinically irrelevant, if any. Serum 25(OH)D also showed a gradual increase over time. Clinicians and researchers should be aware of these changes when interpreting laboratory results in dialysis patients.
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Affiliation(s)
- Carola-Ellen Kleine
- Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine, Orange, CA, USA; Long Beach Veterans Affairs Healthcare System, Long Beach, CA, USA
| | - Yoshitsugu Obi
- Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine, Orange, CA, USA; Long Beach Veterans Affairs Healthcare System, Long Beach, CA, USA
| | - Elani Streja
- Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine, Orange, CA, USA; Long Beach Veterans Affairs Healthcare System, Long Beach, CA, USA
| | - Jui-Ting Hsiung
- Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine, Orange, CA, USA; Long Beach Veterans Affairs Healthcare System, Long Beach, CA, USA
| | - Christina Park
- Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine, Orange, CA, USA; Long Beach Veterans Affairs Healthcare System, Long Beach, CA, USA
| | - Michael F Holick
- Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Kamyar Kalantar-Zadeh
- Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine, Orange, CA, USA; Long Beach Veterans Affairs Healthcare System, Long Beach, CA, USA.
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Vatakencherry RMJ, Saraswathy L. Association between vitamin D and hypertension in people coming for health check up to a tertiary care centre in South India. J Family Med Prim Care 2019; 8:2061-2067. [PMID: 31334180 PMCID: PMC6618207 DOI: 10.4103/jfmpc.jfmpc_236_19] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 03/20/2019] [Accepted: 04/09/2019] [Indexed: 12/13/2022] Open
Abstract
INTRODUCTION Vitamin D has many effects apart from its role in calcium metabolism and bone health. Vitamin D is derived from endogenous ultraviolet-B induced vitamin D synthesis in the skin, and the current high prevalence of vitamin D deficiency in India, can be attributed to lifestyle related low sunlight exposure. Identification of the vitamin D receptor (VDR) in almost all human cells, suggests a role in extra skeletal diseases. Studies have shown that vitamin D deficiency is an independent risk factor for hypertension. AIM To evaluate the association between vitamin D and hypertension in people coming for health check up to a tertiary care center in South India. MATERIALS AND METHODS Study was carried out as a cross sectional study in a tertiary care hospital in South India. Participants (520) were both males and females (337 males and 183 females), between the age group of 20-60 years attending the comprehensive health check up clinic of our hospital. STATISTICAL ANALYSIS Statistical analysis was done using IBM SPSS statistics 20.0. RESULTS Severe vitamin D deficiency was highly prevalent in people with hypertension than in people without hypertension (P value <0.001). CONCLUSION Since India is a tropical country, till recently it was believed that vitamin D deficiency and its ill effects are uncommon. But it was found that, vitamin D deficiency was highly prevalent in people with hypertension in South India, emphasizing the need of early vitamin D supplementation. Therefore, to reduce cardiovascular morbidity, early identification of vitamin D deficiency and appropriate vitamin D supplementation may be of primary importance in population, especially like ours, having high prevalence.
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Affiliation(s)
- Rose Mary J. Vatakencherry
- Department of Physiology, Amrita School of Medicine, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham University, Kochi, Kerala
| | - L Saraswathy
- Department of Physiology, Amrita School of Medicine, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham University, Kochi, Kerala
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Moore LW, Suki WN, Lunsford KE, Sabek OM, Knight RJ, Gaber AO. Cross-sectional evaluation of the relationship between vitamin D status and supplement use across levels of kidney function in adults. BMJ Open 2019; 9:e022471. [PMID: 30798303 PMCID: PMC6398648 DOI: 10.1136/bmjopen-2018-022471] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2018] [Revised: 10/16/2018] [Accepted: 10/19/2018] [Indexed: 01/07/2023] Open
Abstract
OBJECTIVES The objective of this study was to assess vitamin D status of US non-pregnant adults using a standardised assay across 15 mL/min/1.73 m2 increments of kidney function, report the use of dietary supplements containing vitamin D and assess relationships between vitamin D and markers of bone resorption. DESIGN This study is a cross-sectional evaluation. SETTING The study is from the US National Health and Nutrition Evaluation Survey in 2001-2012. PARTICIPANTS The participants were non-institutionalised, non-pregnant adults, age ≥20 years. PRIMARY AND SECONDARY OUTCOME MEASURES The primary outcome measure was serum 25OHD evaluated using liquid chromatography-tandem mass spectroscopy traceable to international reference standards. Secondary outcome measures were use of dietary supplements containing vitamin D and the serum intact parathyroid hormone and bone-specific alkaline phosphatase in a subset of participants. RESULTS The median 25OHD concentration in 27 543 US non-pregnant adults was 25.7 ng/mL (range, 2.2-150.0 ng/mL). Vitamin D supplements were used by 38.0%; mean (SE)=757 (43) international units/day. The range of 25OHD concentration across groups, stratified by kidney function, was 23.0-28.1 ng/mL. The lowest concentration of 25OHD observed was in people with higher kidney function (23.0 ng/mL for estimated glomerular filtration rate >105 mL/min/1.73 m2). Only 24% of people not taking a dietary supplement had a 25OHD concentration >30 ng/mL. Serum intact parathyroid hormone inversely correlated with 25OHD within all kidney function groups. Bone-specific alkaline phosphatase was also negatively associated with 25OHD concentration. CONCLUSIONS These data indicate that 25OHD concentrations and supplement use may be suboptimal in a significant proportion of the population, across all kidney function levels. The response of bone resorption markers further suggests that 25OHD levels could be improved. Together, these data support a re-evaluation of the 25OHD concentration associated with health in adults.
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Affiliation(s)
- Linda W Moore
- Department of Surgery, Houston Methodist Hospital, Houston, Texas, USA
- Center for Outcomes Research, Houston Methodist Research Institute, Houston, TX, USA
| | - Wadi N Suki
- Department of Medicine, Houston Methodist Hospital, Houston, Texas, USA
| | - Keri E Lunsford
- Department of Surgery, Houston Methodist Hospital, Houston, Texas, USA
- Department of Surgery, Weill Cornell Medical College, Houston, Texas, USA
| | - Omaima M Sabek
- Department of Surgery, Houston Methodist Hospital, Houston, Texas, USA
- Department of Surgery, Weill Cornell Medical College, Houston, Texas, USA
| | - Richard J Knight
- Department of Surgery, Houston Methodist Hospital, Houston, Texas, USA
- Department of Surgery, Weill Cornell Medical College, Houston, Texas, USA
| | - A Osama Gaber
- Department of Surgery, Houston Methodist Hospital, Houston, Texas, USA
- Department of Surgery, Weill Cornell Medical College, Houston, Texas, USA
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Stancu S, Chiriac C, Maria D, Mota E, Mircescu G, Capusa C. NUTRITIONAL OR ACTIVE VITAMIN D FOR THE CORRECTION OF MINERAL METABOLISM ABNORMALITIES IN NON-DIALYSIS CHRONIC KIDNEY DISEASE PATIENTS? ACTA ENDOCRINOLOGICA (BUCHAREST, ROMANIA : 2005) 2018; 14:505-513. [PMID: 31149304 PMCID: PMC6516423 DOI: 10.4183/aeb.2018.505] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
CONTEXT Benefits of vitamin D therapies in chronic kidney disease (CKD) are debated. OBJECTIVE To compare the effects of medium-term native (VitD) and active (VDRA) vitamin D on parameters of mineral metabolism and arterial function in non-dialysis CKD. DESIGN Open-label, active comparator, randomized study. SUBJECTS AND METHODS Forty-eight adult patients, vitamin D naïve, CKD stage 3 to 5 with increased parathyroid hormone (iPTH) were randomized to receive either oral cholecalciferol 1000UI/day (n=24) or paricalcitol 1mcg/day (n=24) for 6 months. Median changes at end of study vs. baseline in serum calcidiol, iPTH, total alkaline phosphatase (ALP), and cardio-ankle vascular index (CAVI) were the efficacy parameters. RESULTS Higher increase in calcidiol (15.5 [95%CI 13.3; 17.2] vs. 0.4 [95%CI -6.1; 3.7]ng/mL, p<0.001) were found in VitD group. Conversely, the decline of iPTH (-35.2 [95%CI -83; 9] vs. 13.3 [95%CI -8.1; 35]pg/mL, p=0.008) and ALP (-34 [95%CI -58; -11] vs. -10 [95%CI -23; -2]U/L, p=0.02) were greater after paricalcitol. More subjects experienced iPTH decrease in VDRA group (71% vs. 39%, p=0.03). The variation in CAVI and the incidence of hypercalcemia and hyperphosphatemia were similar. CONCLUSIONS It seems that secondary hyperparathyroidism was more efficiently treated by VDRA, whereas cholecalciferol better corrected the calcidiol deficiency in non-dialysis CKD.
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Affiliation(s)
- S. Stancu
- “Carol Davila” University of Medicine and Pharmacy - Nephrology Department, Romania
- “Dr Carol Davila” Teaching Hospital of Nephrology, Bucharest, Romania
| | - C. Chiriac
- “Carol Davila” University of Medicine and Pharmacy - Nephrology Department, Romania
| | - D.T. Maria
- Emergency County Hospital - Nephrology Department, Craiova, Romania
| | - E. Mota
- Emergency County Hospital - Nephrology Department, Craiova, Romania
| | - G. Mircescu
- “Carol Davila” University of Medicine and Pharmacy - Nephrology Department, Romania
- “Dr Carol Davila” Teaching Hospital of Nephrology, Bucharest, Romania
| | - C. Capusa
- “Carol Davila” University of Medicine and Pharmacy - Nephrology Department, Romania
- “Dr Carol Davila” Teaching Hospital of Nephrology, Bucharest, Romania
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Giannini S, Mazzaferro S, Minisola S, De Nicola L, Rossini M, Cozzolino M. Raising awareness on the therapeutic role of cholecalciferol in CKD: a multidisciplinary-based opinion. Endocrine 2018; 59:242-259. [PMID: 28726185 PMCID: PMC5846860 DOI: 10.1007/s12020-017-1369-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2017] [Accepted: 06/27/2017] [Indexed: 12/19/2022]
Abstract
Vitamin D is recognized to play an essential role in health and disease. In kidney disease, vitamin D analogs have gained recognition for their involvement and potential therapeutic importance. Nephrologists are aware of the use of oral native vitamin D supplementation, however, uncertainty still exists with regard to the use of this treatment option in chronic kidney disease as well as clinical settings related to chronic kidney disease, where vitamin D supplementation may be an appropriate therapeutic choice. Two consecutive meetings were held in Florence in July and November 2016 comprising six experts in kidney disease (N = 3) and bone mineral metabolism (N = 3) to discuss a range of unresolved issues related to the use of cholecalciferol in chronic kidney disease. The panel focused on the following six key areas where issues relating to the use of oral vitamin D remain controversial: (1) vitamin D and parathyroid hormone levels in the general population, (2) cholecalciferol in chronic kidney disease, (3) vitamin D in cardiovascular disease, (4) vitamin D and renal bone disease, (5) vitamin D in rheumatological diseases affecting the kidney, (6) vitamin D and kidney transplantation.
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Affiliation(s)
- Sandro Giannini
- Department of Medicine, Clinica Medica 1, University of Padova, Padova, Italy
| | - Sandro Mazzaferro
- Department of Cardiovascular Respiratory Nephrologic Anesthetic and Geriatric Sciences, Sapienza University of Rome, Rome, Italy
| | - Salvatore Minisola
- Department of Internal Medicine and Medical Disciplines, Sapienza University of Rome, Rome, Italy
| | - Luca De Nicola
- Division of Nephrology, Second University of Naples, Naples, Italy
| | - Maurizio Rossini
- Department of Medicine, Rheumatology Unit, University of Verona, Verona, Italy
| | - Mario Cozzolino
- Department of Health Sciences, Renal Division and Laboratory of Experimental Nephrology, San Paolo Hospital, University of Milan, Milan, Italy.
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Kim HY, Lee YA, Jung HW, Gu MJ, Kim JY, Lee GM, Lee J, Yoon JY, Yang SW, Shin CH. A lack of association between vitamin D-binding protein and 25-hydroxyvitamin D concentrations in pediatric type 1 diabetes without microalbuminuria. Ann Pediatr Endocrinol Metab 2017; 22:247-252. [PMID: 29301185 PMCID: PMC5769838 DOI: 10.6065/apem.2017.22.4.247] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2017] [Revised: 06/02/2017] [Accepted: 06/26/2017] [Indexed: 12/12/2022] Open
Abstract
PURPOSE Vitamin D deficiency is reported to be more common in type 1 diabetes patients and might be associated with the increased urinary loss of vitamin D binding protein (VDBP) consequent to impaired 25-hydroxyvitamin D (25(OH)D) circulation. We aimed to evaluate the possible increased urinary loss of VDBP, a correlation between VDBP and circulating 25(OH)D level, and risk factors influencing low vitamin D level in pediatric type 1 diabetes patients without microalbuminuria. METHODS This is a cross-sectional study of subjects who visited Seoul National University Children's Hospital between January and March 2013. Forty-two type 1 diabetes patients and 29 healthy controls were included. Biochemical parameters including serum and urine VDBP concentrations were analyzed. RESULTS There was no significant difference in the frequency of vitamin D deficiency or serum 25(OH)D level between the 2 groups. The serum and urine VDBP concentrations did not show any difference between the 2 groups. Serum 25(OH) D level did not correlate with serum or urine VDBP. Multivariate regression analysis revealed that daylight outdoor hours (β=2.948, P=0.003) and vitamin D intake (β=2.865, P=0.003) affected the 25(OH)D level; the presence of type 1 diabetes or urinary VDBP excretion was not significant. CONCLUSIONS In pediatric type 1 diabetes patients, urinary VDBP excretion did not contribute to low serum 25(OH)D level in the setting of normoalbuminuria. The factors associated with 25(OH)D level during winter periods were daylight outdoor hours and vitamin D intake. Further studies including both micro- and macroalbuminuria patients with type 1 diabetes are warranted.
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Affiliation(s)
- Hwa Young Kim
- Department of Pediatrics, Kangwon National University Hospital, Chuncheon, Korea
| | - Young Ah Lee
- Department of Pediatrics, Seoul National University Children’s Hospital, Seoul, Korea
| | - Hae Woon Jung
- Department of Pediatrics, Kyung Hee University Medical Center, Seoul, Korea
| | - Min Jeoung Gu
- Department of Pediatrics, Seoul National University Children’s Hospital, Seoul, Korea
| | - Ji Young Kim
- Department of Pediatrics, Seoul National University Children’s Hospital, Seoul, Korea
| | - Gyung Min Lee
- Department of Pediatrics, Konyang University Hospital, Daejeon, Korea
| | - Jieun Lee
- Department of Pediatrics, Inje University Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea
| | - Ju Young Yoon
- Gyeongsang National University Hospital, Changwon, Korea
| | - Sei Won Yang
- Department of Pediatrics, Seoul National University Children’s Hospital, Seoul, Korea
| | - Choong Ho Shin
- Department of Pediatrics, Seoul National University Children’s Hospital, Seoul, Korea,Address for correspondence: Choong Ho Shin, MD, PhD https://orcid.org/0000-0002-9813-1134 Department of Pediatrics, Seoul National University Children’s Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea Tel: +82-2-2072-3357 Fax: +82-2-743-3455 E-mail:
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Mihajlovic M, Fedecostante M, Oost MJ, Steenhuis SKP, Lentjes EGWM, Maitimu-Smeele I, Janssen MJ, Hilbrands LB, Masereeuw R. Role of Vitamin D in Maintaining Renal Epithelial Barrier Function in Uremic Conditions. Int J Mol Sci 2017; 18:ijms18122531. [PMID: 29186865 PMCID: PMC5751134 DOI: 10.3390/ijms18122531] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2017] [Revised: 10/28/2017] [Accepted: 11/22/2017] [Indexed: 12/20/2022] Open
Abstract
As current kidney replacement therapies are not efficient enough for end-stage renal disease (ESRD) treatment, a bioartificial kidney (BAK) device, based on conditionally immortalized human proximal tubule epithelial cells (ciPTEC), could represent an attractive solution. The active transport activity of such a system was recently demonstrated. In addition, endocrine functions of the cells, such as vitamin D activation, are relevant. The organic anion transporter 1 (OAT-1) overexpressing ciPTEC line presented 1α-hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1) and vitamin D receptor (VDR), responsible for vitamin D activation, degradation and function, respectively. The ability to produce and secrete 1α,25-dihydroxy-vitamin D3, was shown after incubation with the precursor, 25-hydroxy-vitamin D3. The beneficial effect of vitamin D on cell function and behavior in uremic conditions was studied in the presence of an anionic uremic toxins mixture. Vitamin D could restore cell viability, and inflammatory and oxidative status, as shown by cell metabolic activity, interleukin-6 (IL-6) levels and reactive oxygen species (ROS) production, respectively. Finally, vitamin D restored transepithelial barrier function, as evidenced by decreased inulin-FITC leakage in biofunctionalized hollow fiber membranes (HFM) carrying ciPTEC-OAT1. In conclusion, the protective effects of vitamin D in uremic conditions and proven ciPTEC-OAT1 endocrine function encourage the use of these cells for BAK application.
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Affiliation(s)
- Milos Mihajlovic
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands.
| | - Michele Fedecostante
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands.
| | - Miriam J Oost
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands.
| | - Sonja K P Steenhuis
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands.
| | - Eef G W M Lentjes
- Department of Clinical Chemistry and Haematology, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands.
| | - Inge Maitimu-Smeele
- Department of Clinical Chemistry and Haematology, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands.
| | - Manoe J Janssen
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands.
| | - Luuk B Hilbrands
- Department of Nephrology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
| | - Rosalinde Masereeuw
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands.
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Levin A, Tang M, Perry T, Zalunardo N, Beaulieu M, Dubland JA, Zerr K, Djurdjev O. Randomized Controlled Trial for the Effect of Vitamin D Supplementation on Vascular Stiffness in CKD. Clin J Am Soc Nephrol 2017; 12:1447-1460. [PMID: 28550081 PMCID: PMC5586581 DOI: 10.2215/cjn.10791016] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2016] [Accepted: 04/17/2017] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND OBJECTIVES Vitamin D is implicated in vascular health in CKD. This study compared placebo, calcifediol, and calcitriol treatment with changes in vascular stiffness, BP, proteinuria, mineral metabolism parameters, C-reactive protein, and fibroblast growth factor 23 in patients with stable CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We conducted a double-blind, randomized controlled trial in out-patient CKD clinics in Vancouver, Canada, from February of 2011 to August of 2014, enrolling 119 patients with an eGFR of 15-45 ml/min per 1.73 m2. Change in pulse wave velocity (PWV) was measured after 6 months of treatment with a fixed dose of oral calcifediol (5000 IU 25-hydroxyvitamin D3), calcitriol (0.5 µg 1,25-dihydroxyvitamin D3), or placebo, thrice weekly. RESULTS Eighty-seven participants were evaluated. Mean age was 66 years, 71% were men, 40% were diabetic, and mean baseline PWV was 11.5 m/s (SD=3.9 m/s). After 6 months, the PWV decreased in the calcifediol group (mean change, -1.1; 95% confidence interval [95% CI], -2.2 to 0.1 m/s), remained unchanged in the calcitriol group (mean change, 0.2; 95% CI, -0.9 to 1.4 m/s), and increased in the placebo group (mean change, 1.1; 95% CI, -0.1 to 2.2 m/s). The overall P value for between-arm changes was 0.03. Absolute PWV change was significantly different between groups (P=0.04): the combined vitamin D treatment group saw decreased PWV (mean change, -0.4; 95% CI, -1.2 to 0.4 m/s) whereas the placebo group saw increased PWV (mean change, +1.1; 95% CI, -0.1 to 2.2 m/s). The treatment group demonstrated significantly decreased serum parathyroid hormone (mean difference, -0.5; 95% CI, -0.7 to -0.3 ln[pg/ml]; P<0.001) and increased calcium (mean difference, 0.4; 95% CI, -0.1 to 0.7 mg/dl; P=0.02). In observational analysis, participants in the highest 25-hydroxyvitamin D tertile at trial end had significant decreases in PWV (mean change, -1.0; 95% CI, -2.0 to 0.0 m/s) compared with the middle and lowest tertiles (P<0.01). Side effects were minor and rare. CONCLUSIONS Six months of supplemental vitamin D analogs at fixed doses may achieve a reduction of PWV in patients with advanced CKD. Because the treatment effect was attenuated when baseline PWV was included as a covariate, these findings should be replicated in larger populations and further studied.
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Affiliation(s)
- Adeera Levin
- Division of Nephrology
- Department of Medicine, and
| | - Mila Tang
- Nephrology Research, St. Paul's Hospital, and
- BC Renal Agency, Vancouver, Canada
| | | | | | - Monica Beaulieu
- Division of Nephrology
- Department of Medicine, and
- BC Renal Agency, Vancouver, Canada
| | - Joshua A. Dubland
- Department of Medicine, and
- Centre for Heart and Lung Innovation, University of British Columbia
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Galassi A, Bellasi A, Ciceri P, Pivari F, Conte F, Cozzolino M. Calcifediol to treat secondary hyperparathyroidism in patients with chronic kidney disease. Expert Rev Clin Pharmacol 2017; 10:1073-1084. [DOI: 10.1080/17512433.2017.1371011] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- Andrea Galassi
- Department of Health Sciences, Renal Division, University of Milan, Milan, Italy
| | - Antonio Bellasi
- Department of Health Sciences, Renal Division, University of Milan, Milan, Italy
- Renal & Dialysis Unit ASST Lariana, S. Anna Hospital, Como, Italy
| | - Paola Ciceri
- Department of Health Sciences, Renal Division, University of Milan, Milan, Italy
| | - Francesca Pivari
- Department of Health Sciences, Renal Division, University of Milan, Milan, Italy
| | - Ferruccio Conte
- Department of Health Sciences, Renal Division, University of Milan, Milan, Italy
| | - Mario Cozzolino
- Department of Health Sciences, Renal Division, University of Milan, Milan, Italy
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Caravaca F, Caravaca-Fontán F, Azevedo L, Luna E. Changes in renal function after discontinuation of vitamin D analogues in advanced chronic kidney disease. Nefrologia 2017; 38:179-189. [PMID: 28676189 DOI: 10.1016/j.nefro.2017.05.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Revised: 04/25/2017] [Accepted: 05/22/2017] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND In routine clinical practice, the prescription of vitamin D analogues (VDA) in patients with chronic kidney disease (CKD) is often associated with a decline of the estimated renal function. The reason for this is not fully understood. AIMS To analyse the effects of VDA discontinuation in advanced CKD and to determine the factors associated with changes in renal function. MATERIAL AND METHODS Retrospective cohort study of adult patients with advanced CKD. The case subgroup was treated with VDA and this medication was discontinued at baseline (the first visit). The control subgroup was not treated with VDA and they were selected according to comparability principles for CKD progression by propensity score matching. The primary outcome measure was a change to both the estimated glomerular filtration rate (MDRD-GFR) and the measured glomerular filtration rate (mGFR by combined creatinine and urea clearances). Baseline parameters related to mineral metabolism and creatinine generation were analysed as potential determinants of renal function changes. RESULTS The study sample consisted of 67 cases and 67 controls. Renal function improved in 67% of cases and worsened in 72% of controls (p<0.0001). Changes in MDRD-GFR for the case subgroup and the control subgroup were +0.455±0.997 vs. -0.436±1.103ml/min/1.73 m2/month (p<0.0001), respectively. Total creatinine excretion was slightly higher in cases than in controls but the difference was not significant. According to multivariate logistic and linear regression analyses, baseline total serum calcium was one of the best determinants of both renal function recovery (Odds ratio=3.49; p=0.001), and of the extent of renal function recovery (beta=0.276; p=0.001). CONCLUSIONS Discontinuation of VDA treatment in CKD patients is associated with significant recovery of estimated renal function. The extent of these changes is mainly associated with baseline total serum calcium.
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Affiliation(s)
| | | | - Lilia Azevedo
- Servicio de Nefrología, Hospital Infanta Cristina, Badajoz, España
| | - Enrique Luna
- Servicio de Nefrología, Hospital Infanta Cristina, Badajoz, España
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Grübler MR, März W, Pilz S, Grammer TB, Trummer C, Müllner C, Schwetz V, Pandis M, Verheyen N, Tomaschitz A, Fiordelisi A, Laudisio D, Cipolletta E, Iaccarino G. Vitamin-D concentrations, cardiovascular risk and events - a review of epidemiological evidence. Rev Endocr Metab Disord 2017; 18:259-272. [PMID: 28451877 DOI: 10.1007/s11154-017-9417-0] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Vitamin D has long been established as an elemental factor of bone physiology. Beyond mineral metabolism, the expression of the vitamin D receptor has been identified throughout the cardiovascular (CV) system. Experimental studies showed beneficial effects of vitamin D on heart and vessels, but vitamin D intoxication in animals also led to hypercalcemia and vascular calcification. Our knowledge has been extended by epidemiological studies that showed that 25-hydroxyvitamin D (25(OH)D) levels are inversely associated with an increased CV risk itself, but also with established CV risk factors, such as arterial hypertension, endothelial dysfunction and atherosclerosis. Conversely, randomized controlled trials could not document significant and consistent effects of vitamin D supplementation on CV risk or events. Potential explanations may lie in differences in reference ranges or the possibility that low vitamin D in CV disease is only an epiphenomenon. In the latter case, the key question is why low 25(OH)D levels are such a strong predictor of health. While we wait for new data, the current conclusion is that vitamin D is a strong risk marker for CV risk factors and for CV diseases itself.
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Affiliation(s)
- Martin Robert Grübler
- Swiss Cardiovascular Centre Bern, Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse 8, 3010, Bern, Switzerland.
- Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria.
| | - Winfried März
- Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, and Rheumatology), Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
- Synlab Academy, Synlab Services GmbH, and Augsburg, Mannheim, Germany
| | - Stefan Pilz
- Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria
- Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, Netherlands
| | - Tanja B Grammer
- Mannheim Institute of Public Health, Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany
| | - Christian Trummer
- Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria
| | - Christian Müllner
- Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria
| | - Verena Schwetz
- Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria
| | - Marlene Pandis
- Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria
| | - Nicolas Verheyen
- Department of Internal Medicine, Division of Cardiology, Medical University of Graz, Graz, Austria
| | - Andreas Tomaschitz
- Department of Internal Medicine, Division of Cardiology, Medical University of Graz, Graz, Austria
- Bad Gleichenberg Clinic, Schweizereiweg 4, 8344, Bad Gleichenberg, Austria
| | | | | | - Ersilia Cipolletta
- Department of Medicine, Surgery Odontoiatrics-Scuola Medica Salernitana, University of Salerno, Salerno, Italy
| | - Guido Iaccarino
- Department of Medicine, Surgery Odontoiatrics-Scuola Medica Salernitana, University of Salerno, Salerno, Italy
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Jean G, Souberbielle JC, Chazot C. Vitamin D in Chronic Kidney Disease and Dialysis Patients. Nutrients 2017; 9:nu9040328. [PMID: 28346348 PMCID: PMC5409667 DOI: 10.3390/nu9040328] [Citation(s) in RCA: 202] [Impact Index Per Article: 25.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2017] [Revised: 03/15/2017] [Accepted: 03/20/2017] [Indexed: 12/17/2022] Open
Abstract
Vitamin D deficiency (<20 ng/mL) and insufficiency (20–29 ng/mL) are common among patients with chronic kidney disease (CKD) or undergoing dialysis. In addition to nutritional and sunlight exposure deficits, factors that affect vitamin D deficiency include race, sex, age, obesity and impaired vitamin D synthesis and metabolism. Serum 1,25(OH)2D levels also decrease progressively because of 25(OH)D deficiency, together with impaired availability of 25(OH)D by renal proximal tubular cells, high fibroblast growth factor (FGF)-23 and decreased functional renal tissue. As in the general population, this condition is associated with increased morbidity and poor outcomes. Together with the progressive decline of serum calcitriol, vitamin D deficiency leads to secondary hyperparathyroidism (SHPT) and its complications, tertiary hyperparathyroidism and hypercalcemia, which require surgical parathyroidectomy or calcimimetics. Kidney Disease Outcomes Quality Initiative (KDOQI) and Kidney Disease Improving Global Outcomes (KDIGO) experts have recognized that vitamin D insufficiency and deficiency should be avoided in CKD and dialysis patients by using supplementation to prevent SHPT. Many vitamin D supplementation regimens using either ergocalciferol or cholecalciferol daily, weekly or monthly have been reported. The benefit of native vitamin D supplementation remains debatable because observational studies suggest that vitamin D receptor activator (VDRA) use is associated with better outcomes and it is more efficient for decreasing the serum parathormone (PTH) levels. Vitamin D has pleiotropic effects on the immune, cardiovascular and neurological systems and on antineoplastic activity. Extra-renal organs possess the enzymatic capacity to convert 25(OH)D to 1,25(OH)2D. Despite many unanswered questions, much data support vitamin D use in renal patients. This article emphasizes the role of native vitamin D replacement during all-phases of CKD together with VDRA when SHPT persists.
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Affiliation(s)
- Guillaume Jean
- NephroCare Tassin Charcot, Sainte Foy les Lyon, 69110, France.
| | - Jean Claude Souberbielle
- Service d'explorations fonctionnelles, Hôpital Necker-Enfants malades, AP-HP, Paris 75015, France.
| | - Charles Chazot
- NephroCare Tassin Charcot, Sainte Foy les Lyon, 69110, France.
- F-CRIN, Investigation Network Initiative-Cardiovascular and Renal Clinical Trialist, Vandoeuvre-lès-Nancy 54500, France.
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The Impact of Homocysteine, Vitamin B12, and Vitamin D Levels on Functional Outcome after First-Ever Ischaemic Stroke. BIOMED RESEARCH INTERNATIONAL 2017; 2017:5489057. [PMID: 28424785 PMCID: PMC5382296 DOI: 10.1155/2017/5489057] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/11/2017] [Revised: 03/04/2017] [Accepted: 03/09/2017] [Indexed: 12/31/2022]
Abstract
We explored the relationship between acute ischaemic stroke (IS) early functional outcome and serum levels of homocysteine, vitamin B12, and D in a noninterventional prospective clinical study. We enrolled 50 patients with first-ever IS and performed laboratory tests and functional assessment at three time points: on admission and three and six months after stroke. Modified Rankin Scale (mRS), NIHSS scale, and Barthel index (BI) scores were assessed in all participants by trained examiner blinded to laboratory data. Patients did not receive treatment that might alter laboratory data. Admission NIHSS correlated with homocysteine levels (r = 0.304, p < 0.05), B12 level (r = −0.410, p < 0.01), and vitamin D levels (r = −0.465, p < 0.01). Functional outcome measures (BI and mRS) did not significantly correlate with homocysteine and vitamin D3 levels at 3 and 6 months. However, a positive correlation with vitamin B12 levels was detected for BI both at 3 and 6 months and mRS at 6 months. Higher serum vitamin B12 levels were associated with better functional outcome at follow-up.
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Hou YC, Liu WC, Zheng CM, Zheng JQ, Yen TH, Lu KC. Role of Vitamin D in Uremic Vascular Calcification. BIOMED RESEARCH INTERNATIONAL 2017; 2017:2803579. [PMID: 28286758 PMCID: PMC5329659 DOI: 10.1155/2017/2803579] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/01/2016] [Revised: 12/26/2016] [Accepted: 01/16/2017] [Indexed: 12/16/2022]
Abstract
The risk of cardiovascular death is 10 times higher in patients with CKD (chronic kidney disease) than in those without CKD. Vascular calcification, common in patients with CKD, is a predictor of cardiovascular mortality. Vitamin D deficiency, another complication of CKD, is associated with vascular calcification in patients with CKD. GFR decline, proteinuria, tubulointerstitial injury, and the therapeutic dose of active form vitamin D aggravate vitamin D deficiency and reduce its pleiotropic effect on the cardiovascular system. Vitamin D supplement for CKD patients provides a protective role in vascular calcification on the endothelium by (1) renin-angiotensin-aldosterone system inactivation, (2) alleviating insulin resistance, (3) reduction of cholesterol and inhibition of foam cell and cholesterol efflux in macrophages, and (4) modulating vascular regeneration. For the arterial calcification, vitamin D supplement provides adjunctive role in regressing proteinuria, reverse renal osteodystrophy, and restoring calcification inhibitors. Recently, adventitial progenitor cell has been linked to be involved in the vascular calcification. Vitamin D may provide a role in modulating adventitial progenitor cells. In summary, vitamin D supplement may provide an ancillary role for ameliorating uremic vascular calcification.
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Affiliation(s)
- Yi-Chou Hou
- Division of Nephrology, Department of Internal Medicine, Cardinal Tien Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
| | - Wen-Chih Liu
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Division of Nephrology, Department of Internal Medicine, Yonghe Cardinal Tien Hospital, New Taipei City, Taiwan
| | - Cai-Mei Zheng
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
| | - Jing-Quan Zheng
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Division of Critical Care Medicine, Department of Emergency Medicine-Critical Care Medicine (EM-CCM), Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
| | - Tzung-Hai Yen
- Department of Nephrology and Division of Clinical Toxicology and Toxicology Laboratory, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan
| | - Kuo-Cheng Lu
- Division of Nephrology, Department of Internal Medicine, Cardinal Tien Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
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Chung S, Kim M, Koh ES, Hwang HS, Chang YK, Park CW, Kim SY, Chang YS, Hong YA. Serum 1,25-dihydroxyvitamin D Better Reflects Renal Parameters Than 25-hydoxyvitamin D in Patients with Glomerular Diseases. Int J Med Sci 2017; 14:1080-1087. [PMID: 29104461 PMCID: PMC5666538 DOI: 10.7150/ijms.20452] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2017] [Accepted: 07/24/2017] [Indexed: 01/21/2023] Open
Abstract
Background: Impaired vitamin D metabolism may contribute to the development and progression of chronic kidney disease. The purpose of this study was to determine associations of circulating vitamin D with the degree of proteinuria and estimated glomerular filtration rate (eGFR) in patients with biopsy-proven glomerular diseases. Methods: Clinical and biochemical data including blood samples for 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) levels were collected from patients at the time of kidney biopsy. Results: Serum 25(OH)D levels were not different according to eGFR. However, renal function was significantly decreased with lower serum 1,25(OH)2D levels (P < 0.001). The proportions of nephrotic-range proteinuria and renal dysfunction (eGFR ≤ 60 mL/min/1.73 m2) progressively increased with declining 1,25(OH)2D but not 25(OH)D. Multivariable linear regression analysis showed that 25(OH)D was significantly correlated with serum albumin and total cholesterol (β = 0.224, P = 0.006; β = -0.263, P = 0.001) and 1,25(OH)2D was significantly correlated with eGFR, serum albumin and phosphorus (β = 0.202, P = 0.005; β = 0.304, P < 0.001; β = -0.161, P = 0.024). In adjusted multivariable linear regression, eGFR and 24hr proteinuria were independently correlated only with 1,25(OH)2D (β = 0.154, P = 0.018; β = -0.171, P = 0.012), but not 25(OH)D. The lower level of 1,25(OH)2D was associated with the frequent use of immunosuppressive agents (P < 0.001). Conclusion: It is noteworthy in these results that circulating 1,25(OH)2D may be superior to 25(OH)D as a marker of severity of glomerular diseases.
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Affiliation(s)
- Sungjin Chung
- Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.,Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Minyoung Kim
- Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Eun Sil Koh
- Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Hyeon Seok Hwang
- Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Yoon Kyung Chang
- Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Cheol Whee Park
- Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Suk Young Kim
- Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Yoon Sik Chang
- Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Yu Ah Hong
- Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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Agarwal G, Hirachan P, Gelfond J, Fanti P, Hura C, Bansal S. Ergocalciferol treatment does Not improve erythropoietin utilization and hospitalization rate in hemodialysis patients. BMC Nephrol 2016; 17:144. [PMID: 27717322 PMCID: PMC5055677 DOI: 10.1186/s12882-016-0359-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2016] [Accepted: 09/28/2016] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Vitamin D (25-hydroxyvitamin D; 25[OH]D) deficiency (VDD) is highly prevalent in chronic kidney disease. The aim of this study was to evaluate the effect of oral ergocalciferol supplementation on requirement of erythropoietin (EPO) and active vitamin D analogues, and hospitalization rate in maintenance hemodialysis (HD) patients. METHODS This retrospective cohort study included 186 patients who were on HD for 3 months and had 25(OH)D levels < 30 ng/ml. Over 1-year period, 107 patients were supplemented with protocol-based ergocalciferol (D2 group) and 79 were not (control). Parameters of erythropoiesis and bone-mineral metabolism, and monthly doses of EPO and paricalcitol were assessed at 6- and 12- months of ergocalciferol supplementation. Total hospitalizations were recorded for the same year. RESULTS Baseline characteristics were similar across two arms except higher serum ferritin, transferrin saturation and prevalence of stroke in D2 and higher coronary artery disease in control group with overall mean ± SD 25(OH)D level of 16.8 ± 7 ng/ml. At 12 months, 25(OH)D levels increased significantly in D2 group compared to control (30.5 ± 11.7 vs. 14.2 ± 9.3 ng/ml; p < 0.001). The EPO dose remained same with no difference in hemoglobin values between the two groups during the intervention period. On multivariate regression which included above variables there was no effect of ergocalciferol treatment on EPO dose (p = ns). Hospitalization rate was similar in two arms; however, ergocalciferol treatment inversely associated with paricalcitol dose (β ± SE = -10.4 ± 2.8; p < 0.001). CONCLUSIONS One-year of ergocalciferol supplementation was not associated with reduction in EPO requirement or hospitalization rate in HD patients with VDD. Further studies are warranted to determine definitive role of nutritional vitamin D in these patients.
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Affiliation(s)
- Gaurav Agarwal
- Department of Medicine, Division of Nephrology, University of Alabama at Birmingham School of Medicine, Birmingham, AL USA
| | - Padam Hirachan
- Department of Medicine, Division of Nephrology, University of Texas Health Sciences Center at San Antonio, 7703 Floyd Curl Drive, MSC 7882, San Antonio, TX 78229 USA
| | - Jonathan Gelfond
- Department of Epidemiology and Biostatistics, University of Texas Health Sciences Center at San Antonio, San Antonio, TX USA
| | - Paolo Fanti
- Department of Medicine, Division of Nephrology, University of Texas Health Sciences Center at San Antonio, 7703 Floyd Curl Drive, MSC 7882, San Antonio, TX 78229 USA
| | - Claudia Hura
- Department of Medicine, Division of Nephrology, University of Texas Health Sciences Center at San Antonio, 7703 Floyd Curl Drive, MSC 7882, San Antonio, TX 78229 USA
| | - Shweta Bansal
- Department of Medicine, Division of Nephrology, University of Texas Health Sciences Center at San Antonio, 7703 Floyd Curl Drive, MSC 7882, San Antonio, TX 78229 USA
- Renal Section, South Texas Veterans HealthCare System, San Antonio, TX USA
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