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Kotowska K, Wojciuk B, Sieńko J, Bogacz A, Stukan I, Drożdżal S, Czerny B, Tejchman K, Trybek G, Machaliński B, Kotowski M. The Role of Vitamin D Metabolism Genes and Their Genomic Background in Shaping Cyclosporine A Dosage Parameters after Kidney Transplantation. J Clin Med 2024; 13:4966. [PMID: 39201108 PMCID: PMC11355102 DOI: 10.3390/jcm13164966] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 08/12/2024] [Accepted: 08/19/2024] [Indexed: 09/02/2024] Open
Abstract
Background: Kidney transplantation is followed by immunosuppressive therapy involving calcineurin inhibitors (CNIs) such as cyclosporin A. However, long-term high CNIs doses can lead to vitamin D deficiency, and genetic variations influencing vitamin D levels can indirectly impact the necessary CNIs dosage. This study investigates the impact of genetic variations of vitamin D binding protein (DBP) rs2282679 and CYP2R1 hydroxylase rs10741657 polymorphisms on the cyclosporin A dosage in kidney transplant recipients. Additional polymorphisims of genes that are predicted to influence the pharmacogenetic profile were included. Methods: Gene polymorphisms in 177 kidney transplant recipients were analyzed using data mining techniques, including the Random Forest algorithm and Classification and Regression Trees (C&RT). The relationship between the concentration/dose (C/D) ratio of cyclosporin A and genetic profiles was assessed to determine the predictive value of DBP rs2282679 and CYP2R1 rs10741657 polymorphisms. Results: Polymorphic variants of the DBP (rs2282679) demonstrated a strong predictive value for the cyclosporin A C/D ratio in post-kidney transplantation patients. By contrast, the CYP2R1 polymorphism (rs10741657) did not show predictive significance. Additionally, the immune response genes rs231775 CTLA4 and rs1800896 IL10 were identified as predictors of cyclosporin A response, though these did not result in statistically significant differences. Conclusions:DBP rs2282679 polymorphisms can significantly predict the cyclosporin A C/D ratio, potentially enhancing the accuracy of CNI dosing. This can help identify patient groups at risk of vitamin D deficiency, ultimately improving the management of kidney transplant recipients. Understanding these genetic influences allows for more personalized and effective treatment strategies, contributing to better long-term outcomes for patients.
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Affiliation(s)
- Katarzyna Kotowska
- Clinic of Maxillofacial Surgery, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland
| | - Bartosz Wojciuk
- Department of Immunological Diagnostics, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland
| | - Jerzy Sieńko
- Institute of Physical Culture Sciences, University of Szczecin, 70-453 Szczecin, Poland
| | - Anna Bogacz
- Department of Personalized Medicine and Cell Therapy, Regional Blood Center, 60-354 Poznan, Poland
| | - Iga Stukan
- Department of General Pathology, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland
| | - Sylwester Drożdżal
- Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland
| | - Bogusław Czerny
- Department of General Pharmacology and Pharmacoeconomics, Pomeranian Medical University in Szczecin, 71-210 Szczecin, Poland
| | - Karol Tejchman
- Department of General Surgery and Transplantation, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland
| | - Grzegorz Trybek
- Department of Interdisciplinary Dentistry, Pomeranian Medical University, 70-204 Szczecin, Poland
| | - Bogusław Machaliński
- Department of General Pathology, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland
| | - Maciej Kotowski
- Department of General Surgery and Transplantation, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland
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Duan S, Lu F, Sun R, Chen C, Chen S, Geng L, Qian L, Pan Y, Zhang C, Zeng M, Sun B, Mao H, Zhang B, Xing C, Yuan Y. 25(OH)D level and vascular lesion scores in kidney histopathology as risk-stratification tool for predicting renal progression in people with type 2 diabetes. Diabetes Metab Syndr 2024; 18:103037. [PMID: 38744090 DOI: 10.1016/j.dsx.2024.103037] [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: 06/21/2023] [Revised: 05/02/2024] [Accepted: 05/03/2024] [Indexed: 05/16/2024]
Abstract
AIM To evaluate the potential of the combined individual vascular histopathological lesion and serum 25-hydroxy vitamin D [25(OH)D] level as predictors of outcomes in patients with diabetes and chronic kidney disease. METHODS A total of 190 patients with type 2 diabetes and kidney disease stages 1-4 were retrospectively included. Kaplan-Meier analysis and the log-rank test were performed to assess renal survival differences. And the time-dependent receiver operating characteristic analyses were used to characterize the predictive accuracy. Hazard ratios for vascular lesion scores and 25(OH)D levels with renal outcomes were estimated using Cox proportional hazards regression models with follow-up time. RESULTS Over a median follow-up of 23.78 (12.61, 37.14) months, 71 patients (37.4 %) experienced the renal outcomes. Enrolled patients with more severe vascular lesions had worse kidney function, heavier proteinuria, lower serum 25(OH)D levels, and higher prevalence of composite kidney outcomes. Baseline serum 25(OH)D was a significant independent risk factor for vascular lesion scores. The effect of serum 25(OH)D level on kidney prognosis was more pronounced in males and those with more exacerbated vascular lesions (score 2). The severity of vascular lesions and serum 25(OH)D levels were associated with unfavorable kidney outcomes. Accordingly, further time-dependent receiver operating characteristic curves confirmed that combined 25(OH)D level and vascular lesion score had a stable and reliable performance in renal outcomes prediction at short and long-term follow-up times. CONCLUSIONS 25(OH)D level and vascular lesion scores in kidney histopathology could serve as a useful risk-stratification tool for predicting renal progression in patients with type 2 diabetes.
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Affiliation(s)
- Suyan Duan
- Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China
| | - Fang Lu
- Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China
| | - Rui Sun
- Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China
| | - Chen Chen
- Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China
| | - Si Chen
- Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China
| | - Luhan Geng
- Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China
| | - Li Qian
- Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China
| | - Ying Pan
- Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China
| | - Chengning Zhang
- Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China
| | - Ming Zeng
- Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China
| | - Bin Sun
- Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China
| | - Huijuan Mao
- Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China
| | - Bo Zhang
- Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China.
| | - Changying Xing
- Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China.
| | - Yanggang Yuan
- Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China.
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Cui P, Hou H, Song B, Xia Z, Xu Y. Vitamin D and ischemic stroke - Association, mechanisms, and therapeutics. Ageing Res Rev 2024; 96:102244. [PMID: 38395199 DOI: 10.1016/j.arr.2024.102244] [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: 08/17/2023] [Revised: 02/07/2024] [Accepted: 02/19/2024] [Indexed: 02/25/2024]
Abstract
Confronting the rising tide of ischemic stroke and its associated mortality and morbidity with ageing, prevention and acute management of ischemic stroke is of paramount importance. Mounting observational studies have established a non-linear association of vitamin D status with cardiovascular diseases, including ischemic stroke. Paradoxically, current clinical trials fail to demonstrate the cardiovascular benefits of vitamin D supplementation. We aim to update recent clinical and experimental findings on the role of vitamin D in the disease course of ischemic stroke, from its onset, progression, recovery, to recurrence, and the established and alternative possible pathophysiological mechanisms. This review justifies the necessities to address stroke etiological subtypes and focus on vitamin D-deficient subjects for investigating the potential of vitamin D supplementation as a preventive and therapeutic approach for ischemic stroke. Well-powered clinical trials are warranted to determine the efficacy, safety, timing, target individuals, optimal dosages, and target 25OHD concentrations of vitamin D supplementation in the prevention and treatment of ischemic stroke.
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Affiliation(s)
- Pan Cui
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; NHC Key Laboratory of Prevention and Treatment of Cerebrovascular Diseases, Zhengzhou, Henan, China; Clinical Systems Biology Laboratories, Translation Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China
| | - Haiman Hou
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Bo Song
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; NHC Key Laboratory of Prevention and Treatment of Cerebrovascular Diseases, Zhengzhou, Henan, China
| | - Zongping Xia
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; NHC Key Laboratory of Prevention and Treatment of Cerebrovascular Diseases, Zhengzhou, Henan, China; Clinical Systems Biology Laboratories, Translation Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
| | - Yuming Xu
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; NHC Key Laboratory of Prevention and Treatment of Cerebrovascular Diseases, Zhengzhou, Henan, China; Henan Key Laboratory of Cerebrovascular Diseases, Zhengzhou University, Zhengzhou, Henan, China.
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Dey SK, Kumar S, Rani D, Maurya SK, Banerjee P, Verma M, Senapati S. Implications of vitamin D deficiency in systemic inflammation and cardiovascular health. Crit Rev Food Sci Nutr 2023; 64:10438-10455. [PMID: 37350746 DOI: 10.1080/10408398.2023.2224880] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/24/2023]
Abstract
Clinical, epidemiological, and molecular studies have sufficiently highlighted the vitality of vitamin D [25(OH)D and 1,25(OH)2D] in human health and wellbeing. Globally, vitamin D deficiency (VDD) has become a public health concern among all age groups. There is a very high prevalence of VDD per the estimates from several epidemiological studies on different ethnic populations. But, population-specific scales do not support these estimates to define VDD clinically and consistent genetic associations. However, clinical studies have shown the relevance of serum vitamin D screening and oral supplementation in improving health conditions, pointing toward a more prominent role of vitamin D in health and wellness. Routinely, the serum concentration of vitamin D is measured to determine the deficiency and is correlated with physiological conditions and clinical symptoms. Recent research points toward a more inclusive role of vitamin D in different disease pathologies and is not just limited to otherwise bone health and overall growth. VDD contributes to the natural history of systemic ailments, including cardiovascular and systemic immune diseases. Considering its significant impact on premature morbidity and mortality, there is a compelling need to comprehensively review and document the direct and indirect implications of VDD in immune system deregulation, systemic inflammatory conditions, and cardio-metabolism. The recommendations from this review call for furthering our research concerning vitamin D and its direct and indirect implications.
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Affiliation(s)
- Sanjay Kumar Dey
- Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India
| | - Shashank Kumar
- Department of Biochemistry, Central University of Punjab, Bathinda, Punjab, India
| | - Diksha Rani
- Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India
| | | | - Pratibha Banerjee
- Immunogenomics Laboratory, Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bathinda, Punjab, India
| | - Madhur Verma
- Department of Community and Family Medicine, All India Institute of Medical Sciences, Bathinda, Punjab, India
| | - Sabyasachi Senapati
- Immunogenomics Laboratory, Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bathinda, Punjab, India
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AlNafea HM, Korish AA. The interplay between hypovitaminosis D and the immune dysfunction in the arteriovenous thrombotic complications of the sever coronavirus disease 2019 (COVID-19) infection. Blood Coagul Fibrinolysis 2023; 34:129-137. [PMID: 36966750 PMCID: PMC10089932 DOI: 10.1097/mbc.0000000000001212] [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: 01/25/2023] [Accepted: 02/11/2023] [Indexed: 03/28/2023]
Abstract
Thromboembolic complications including cerebrovascular accidents, pulmonary embolism, myocardial infarction, deep vein thrombosis and disseminating intravascular coagulopathy are serious encounters in sever coronavirus disease 2019 (COVID-19) infected patients. This worsens the prognosis and may lead to death or life long morbidities. The laboratory finding of the disturbed haemostasias and the hyperinflammatory response are almost invariably present in COVID-19 patients. Multiple treatment modalities are utilized by the healthcare professionals to overcome the cytokine storm, oxidative stress, endothelial dysfunction, and coagulopathy in these patients. The combined actions of vitamin D (VitD) as a steroid hormone with anti-inflammatory, immunomodulatory, and antithrombotic properties increase the potential of the possible involvement of hypovitaminosis D in the thromboembolic complications of COVID-19 infection, and stimulated researchers and physicians to administer VitD therapy to prevent the infection and/or overcome the disease complications. The current review highlighted the immunomodulatory, anti-inflammatory, antioxidative and hemostatic functions of VitD and its interrelation with the renin-angiotensin-aldosterone system (RAAS) pathway and the complement system. Additionally, the association of VitD deficiency with the incidence and progression of COVID-19 infection and the associated cytokine storm, oxidative stress, hypercoagulability, and endothelial dysfunction were emphasized. Normalizing VitD levels by daily low dose therapy in patients with hypovitaminosis D below (25 nmol/l) is essential for a balanced immune response and maintaining the health of the pulmonary epithelium. It protects against upper respiratory tract infections and decreases the complications of COVID-19 infections. Understanding the role of VitD and its associated molecules in the protection against the coagulopathy, vasculopathy, inflammation, oxidative stress and endothelial dysfunction in COVID-19 infection could lead to new therapeutic strategies to prevent, treat, and limit the complications of this deadly virus infection.
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Affiliation(s)
- Haifa M. AlNafea
- Clinical Laboratory Sciences Department, College of Applied Medical Sciences, King Saud University
| | - Aida A. Korish
- Physiology Department (29), College of Medicine, King Saud University Medical City (KSUMC), King Saud university, Riyadh, Saudi Arabia
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Abstract
Vitamin D represents a group of secosteroids involved in the calcium and phosphate metabolism. The active form of vitamin D, 1,25-dihydroxylcalciferol, exerts its biological mechanisms via the VDR (vitamin D receptor) which acts as a regulator of several target genes. Hypovitaminosis D is associated with many diseases, which are not only limited to the metabolism of the skeleton, but growing evidence links the deficit of vitamin D to cardiovascular, metabolic, immune, and neoplastic diseases. In regard to the cardiovascular system, current evidence shows the presence of VDR in endothelial cells. Moreover, both in vitro and animal experimental models demonstrated that the deficit of vitamin D can promote endothelial dysfunction and atherosclerosis development. Vitamin D can interfere with vascular functions also by affecting the production of vasodilator mediators. VDR is also expressed in left ventricle cardiomyocytes, and hypovitaminosis D can relate to cardiac hypertrophy and heart failure. Randomized clinical trials (RCT) designed to prove the therapeutic role of vitamin D supplementation have been inconclusive to date. The aim of this review is to highlight the main interactions between vitamin D metabolism and cardiovascular diseases; thus, focusing on pathogenic mechanisms and related clinical manifestations.
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Grazioli E, Romani A, Marrone G, Di Lauro M, Cerulli C, Urciuoli S, Murri A, Guerriero C, Tranchita E, Tesauro M, Parisi A, Di Daniele N, Noce A. Impact of Physical Activity and Natural Bioactive Compounds on Endothelial Dysfunction in Chronic Kidney Disease. Life (Basel) 2021; 11:841. [PMID: 34440585 PMCID: PMC8402113 DOI: 10.3390/life11080841] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Revised: 07/21/2021] [Accepted: 08/11/2021] [Indexed: 12/12/2022] Open
Abstract
Chronic kidney disease (CKD) represents a world-wide public health problem. Inflammation, endothelial dysfunction (ED) and vascular calcifications are clinical features of CKD patients that increase cardiovascular (CV) mortality. CKD-related CV disease pathogenic mechanisms are not only associated with traditional factors such as arterial hypertension and dyslipidemia, but also with ED, oxidative stress and low-grade inflammation. The typical comorbidities of CKD contribute to reduce the performance and the levels of the physical activity in nephropathic patients compared to healthy subjects. Currently, the effective role of physical activity on ED is still debated, but the available few literature data suggest its positive contribution. Another possible adjuvant treatment of ED in CKD patients is represented by natural bioactive compounds (NBCs). Among these, minor polar compounds of extra virgin olive oil (hydroxytyrosol, tyrosol and oleocanthal), polyphenols, and vitamin D seem to exert a beneficial role on ED in CKD patients. The objective of the review is to evaluate the effectiveness of physical exercise protocols and/or NBCs on ED in CKD patients.
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Affiliation(s)
- Elisa Grazioli
- Department of Exercise, Human and Health Sciences, Foro Italico University of Rome, 00135 Rome, Italy; (E.G.); (C.C.); (A.M.); (E.T.); (A.P.)
| | - Annalisa Romani
- PHYTOLAB (Pharmaceutical, Cosmetic, Food Supplement, Technology and Analysis), DiSIA, University of Florence, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy; (A.R.); (S.U.)
| | - Giulia Marrone
- UOC of Internal Medicine—Center of Hypertension and Nephrology Unit, Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy; (G.M.); (M.D.L.); (C.G.); (N.D.D.)
| | - Manuela Di Lauro
- UOC of Internal Medicine—Center of Hypertension and Nephrology Unit, Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy; (G.M.); (M.D.L.); (C.G.); (N.D.D.)
| | - Claudia Cerulli
- Department of Exercise, Human and Health Sciences, Foro Italico University of Rome, 00135 Rome, Italy; (E.G.); (C.C.); (A.M.); (E.T.); (A.P.)
| | - Silvia Urciuoli
- PHYTOLAB (Pharmaceutical, Cosmetic, Food Supplement, Technology and Analysis), DiSIA, University of Florence, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy; (A.R.); (S.U.)
| | - Arianna Murri
- Department of Exercise, Human and Health Sciences, Foro Italico University of Rome, 00135 Rome, Italy; (E.G.); (C.C.); (A.M.); (E.T.); (A.P.)
| | - Cristina Guerriero
- UOC of Internal Medicine—Center of Hypertension and Nephrology Unit, Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy; (G.M.); (M.D.L.); (C.G.); (N.D.D.)
| | - Eliana Tranchita
- Department of Exercise, Human and Health Sciences, Foro Italico University of Rome, 00135 Rome, Italy; (E.G.); (C.C.); (A.M.); (E.T.); (A.P.)
| | - Manfredi Tesauro
- UOC of Internal Medicine—Center of Hypertension and Nephrology Unit, Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy; (G.M.); (M.D.L.); (C.G.); (N.D.D.)
| | - Attilio Parisi
- Department of Exercise, Human and Health Sciences, Foro Italico University of Rome, 00135 Rome, Italy; (E.G.); (C.C.); (A.M.); (E.T.); (A.P.)
| | - Nicola Di Daniele
- UOC of Internal Medicine—Center of Hypertension and Nephrology Unit, Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy; (G.M.); (M.D.L.); (C.G.); (N.D.D.)
| | - Annalisa Noce
- UOC of Internal Medicine—Center of Hypertension and Nephrology Unit, Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy; (G.M.); (M.D.L.); (C.G.); (N.D.D.)
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Lu PH, Yu MC, Wei MJ, Kuo KL. The Therapeutic Strategies for Uremic Toxins Control in Chronic Kidney Disease. Toxins (Basel) 2021; 13:573. [PMID: 34437444 PMCID: PMC8402511 DOI: 10.3390/toxins13080573] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Revised: 08/04/2021] [Accepted: 08/16/2021] [Indexed: 12/27/2022] Open
Abstract
Uremic toxins (UTs) are mainly produced by protein metabolized by the intestinal microbiota and converted in the liver or by mitochondria or other enzymes. The accumulation of UTs can damage the intestinal barrier integrity and cause vascular damage and progressive kidney damage. Together, these factors lead to metabolic imbalances, which in turn increase oxidative stress and inflammation and then produce uremia that affects many organs and causes diseases including renal fibrosis, vascular disease, and renal osteodystrophy. This article is based on the theory of the intestinal-renal axis, from bench to bedside, and it discusses nonextracorporeal therapies for UTs, which are classified into three categories: medication, diet and supplement therapy, and complementary and alternative medicine (CAM) and other therapies. The effects of medications such as AST-120 and meclofenamate are described. Diet and supplement therapies include plant-based diet, very low-protein diet, probiotics, prebiotics, synbiotics, and nutraceuticals. The research status of Chinese herbal medicine is discussed for CAM and other therapies. This review can provide some treatment recommendations for the reduction of UTs in patients with chronic kidney disease.
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Affiliation(s)
- Ping-Hsun Lu
- Department of Chinese Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei 23142, Taiwan; (P.-H.L.); (M.-C.Y.); (M.-J.W.)
- School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien 97048, Taiwan
| | - Min-Chien Yu
- Department of Chinese Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei 23142, Taiwan; (P.-H.L.); (M.-C.Y.); (M.-J.W.)
- School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien 97048, Taiwan
| | - Meng-Jiun Wei
- Department of Chinese Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei 23142, Taiwan; (P.-H.L.); (M.-C.Y.); (M.-J.W.)
| | - Ko-Lin Kuo
- Division of Nephrology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei 23142, Taiwan
- School of Medicine, Buddhist Tzu Chi University, Hualien 97048, Taiwan
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Al-Ishaq RK, Kubatka P, Brozmanova M, Gazdikova K, Caprnda M, Büsselberg D. Health implication of vitamin D on the cardiovascular and the renal system. Arch Physiol Biochem 2021; 127:195-209. [PMID: 31291127 DOI: 10.1080/13813455.2019.1628064] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Vitamin D regulates the calcium and phosphorus balance in the body. The activated form of vitamin D (1 α,25-dihydroxyvitamin D) binds to vitamin D receptor which regulates genes that control cell proliferation, differentiation and apoptosis. In the cardiovascular system, the vitamin D receptor is present in cardiomyocytes and the arterial wall. A clear correlation between vitamin D level and cardiovascular diseases is established. Vitamin D deficiency affects the renin-angiotensin system leading to ventricular hypertrophy and eventually to stroke. While clinical trials highlighted the positive effects of vitamin D supplements on cardiovascular disease these still need to be confirmed. This review outlines the association between vitamin D and cardiovascular and renal disease summarising the experimental data of selective cardiovascular disorders.
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Affiliation(s)
| | - Peter Kubatka
- Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia
- Division of Oncology, Biomedical Center Martin, Jessenius Faculty of Medicine, Comenius University, in Bratislava, Martin, Slovakia
| | - Martina Brozmanova
- Department of Pathophysiology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia
- Biomedical Center Martin, Jessenius Faculty of Medicine, Comenius University, in Bratislava, Martin, Slovakia
| | - Katarina Gazdikova
- Department of Nutrition, Faculty of Nursing and Professional Health Studies, Slovak Medical University, Bratislava, Slovak
- Department of General Medicine, Faculty of Medicine, Slovak Medical University, Bratislava, Slovak
| | - Martin Caprnda
- 1st Department of Internal Medicine, Faculty of Medicine, Comenius University and University Hospital, Bratislava, Slovakia
| | - Dietrich Büsselberg
- Department of Physiology and Biophysics, Weill Cornell College of Medicine, Doha, Qatar
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Vitamin D and Cardiovascular Disease, with Emphasis on Hypertension, Atherosclerosis, and Heart Failure. Int J Mol Sci 2020; 21:ijms21186483. [PMID: 32899880 PMCID: PMC7555466 DOI: 10.3390/ijms21186483] [Citation(s) in RCA: 157] [Impact Index Per Article: 31.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Revised: 08/24/2020] [Accepted: 08/31/2020] [Indexed: 12/14/2022] Open
Abstract
Vitamin D deficiency is the most common nutritional deficiency, affecting almost one billion people worldwide. Vitamin D is mostly known for its role in intestinal calcium absorption and bone mineralization. However, the observation of seasonal changes in blood pressure and the subsequent identification of vitamin D receptor (VDR) and 1α-hydroxylase in cardiomyocytes, as well as endothelial and vascular smooth muscle cells, implicated a role of vitamin D in the cardiovascular system. Animal studies provided compelling evidence that vitamin D signaling is essential for cardiovascular integrity, especially for the regulation of vascular tone and as an antifibrotic and antihypertrophic signaling pathway in the heart. In addition, observational studies reported an association between vitamin D deficiency and risk of hypertension, atherosclerosis, and heart failure. However, recent clinical intervention studies failed to prove the causal relationship between vitamin D supplementation and beneficial effects on cardiovascular health. In this review, we aim to highlight our current understanding of the role of vitamin D in the cardiovascular system and to find potential explanations for the large discrepancies between the outcome of experimental studies and clinical intervention trials.
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Kim DH, Meza CA, Clarke H, Kim JS, Hickner RC. Vitamin D and Endothelial Function. Nutrients 2020; 12:E575. [PMID: 32098418 PMCID: PMC7071424 DOI: 10.3390/nu12020575] [Citation(s) in RCA: 182] [Impact Index Per Article: 36.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2020] [Revised: 02/19/2020] [Accepted: 02/19/2020] [Indexed: 12/21/2022] Open
Abstract
Vitamin D is known to elicit a vasoprotective effect, while vitamin D deficiency is a risk factor for endothelial dysfunction (ED). ED is characterized by reduced bioavailability of a potent endothelium-dependent vasodilator, nitric oxide (NO), and is an early event in the development of atherosclerosis. In endothelial cells, vitamin D regulates NO synthesis by mediating the activity of the endothelial NO synthase (eNOS). Under pathogenic conditions, the oxidative stress caused by excessive production of reactive oxygen species (ROS) facilitates NO degradation and suppresses NO synthesis, consequently reducing NO bioavailability. Vitamin D, however, counteracts the activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase which produces ROS, and improves antioxidant capacity by enhancing the activity of antioxidative enzymes such as superoxide dismutase. In addition to ROS, proinflammatory mediators such as TNF-α and IL-6 are risk factors for ED, restraining NO and eNOS bioactivity and upregulating the expression of various atherosclerotic factors through the NF-κB pathway. These proinflammatory activities are inhibited by vitamin D by suppressing NF-κB signaling and production of proinflammatory cytokines. In this review, we discuss the diverse activities of vitamin D in regulating NO bioavailability and endothelial function.
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Affiliation(s)
- Do-Houn Kim
- Department of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, FL 32306, USA; (D.-H.K.); (C.A.M.); (H.C.); (J.-S.K.)
- Center for Advancing Exercise and Nutrition Research on Aging, Florida State University, Tallahassee, FL 32306, USA
| | - Cesar A. Meza
- Department of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, FL 32306, USA; (D.-H.K.); (C.A.M.); (H.C.); (J.-S.K.)
| | - Holly Clarke
- Department of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, FL 32306, USA; (D.-H.K.); (C.A.M.); (H.C.); (J.-S.K.)
| | - Jeong-Su Kim
- Department of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, FL 32306, USA; (D.-H.K.); (C.A.M.); (H.C.); (J.-S.K.)
- Center for Advancing Exercise and Nutrition Research on Aging, Florida State University, Tallahassee, FL 32306, USA
- Institute of Sports Sciences and Medicine, College of Human Sciences, Florida State University, Tallahassee, FL 32306, USA
| | - Robert C. Hickner
- Department of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, FL 32306, USA; (D.-H.K.); (C.A.M.); (H.C.); (J.-S.K.)
- Institute of Sports Sciences and Medicine, College of Human Sciences, Florida State University, Tallahassee, FL 32306, USA
- Department of Biokinetics, Exercise and Leisure Sciences, School of Health Sciences, University of KwaZulu-Natal, Westville 4041, South Africa
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12
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Ergocalciferol improves endothelial vasodilatory and vasoconstrictor function in an in vivo model of mild uraemia. Biosci Rep 2019; 39:221375. [PMID: 31789348 PMCID: PMC6923332 DOI: 10.1042/bsr20190711] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2019] [Revised: 11/20/2019] [Accepted: 11/21/2019] [Indexed: 01/21/2023] Open
Abstract
Endothelial dysfunction and vitamin D deficiency are prevalent in patients with cardiovascular disease (CVD) and chronic kidney disease (CKD). Both are risk factors for cardiovascular events in patients with CKD. No studies have investigated the effect of nutritional forms of vitamin D on endothelial function in earlier stages of CKD, when vascular endothelium may be more amenable to this therapy. We studied the effect of ergocalciferol in a pre-clinical model of mild uraemia. Male Wistar rats underwent either a 5/6th nephrectomy or sham surgery. Four weeks after the final stage of the surgery, these two groups were randomly allocated to placebo or an oral dose of 1000 iu of ergocalcfierol at day 7 and 2 pre sacrifice. Vascular responses to acetylcholine, Spermine NONOate and phenylephrine were determined in aortic rings. Blood pressure, calcium, phosphate and parathyroid hormone were measured in all groups. Ergocalciferol significantly improved the endothelium-dependent responses to acetylcholine and overcame the blunting of the contractile response to phenylephrine seen in uraemic animals. Ergocalciferol improved the contractile response to potassium chloride in uraemic, but not sham animals. All effects occurred independently of changes to calcium, phosphate, parathyroid hormone and systolic blood pressure. There were no differences in endothelium-independent relaxation to Spermine NONOate. In summary, in a model of mild uraemia, ergocalciferol improved vasodilator and vasoconstrictor tone independently of blood pressure and bone mineral parameters suggesting a direct effect of ergocalciferol on the endothelium.
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13
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Alfieri C, Ruzhytska O, Vettoretti S, Caldiroli L, Cozzolino M, Messa P. Native Hypovitaminosis D in CKD Patients: From Experimental Evidence to Clinical Practice. Nutrients 2019; 11:E1918. [PMID: 31443249 PMCID: PMC6723756 DOI: 10.3390/nu11081918] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Revised: 08/07/2019] [Accepted: 08/12/2019] [Indexed: 12/12/2022] Open
Abstract
Native hypovitaminosis D (n-hVITD) is frequently found from the early stages of chronic kidney disease (CKD) and its prevalence increases with CKD progression. Even if the implications of n-hVITD in chronic kidney disease-mineral bone disorder (CKD-MBD) have been extensively characterized in the literature, there is a lot of debate nowadays about the so called "unconventional effects" of native vitamin D (25(OH)VitD) supplementation in CKD patients. In this review, highlights of the dimension of the problem of n-hVITD in CKD stages 2-5 ND patients will be presented. In addition, it will focus on the "unconventional effects" of 25(OH)VitD supplementation, the clinical impact of n-hVITD and the most significant interventional studies regarding 25(OH)VitD supplementation in CKD stages 2-5 ND.
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Affiliation(s)
- Carlo Alfieri
- Nephrology, Dialysis and Renal Transplantation, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
- Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy
| | - Oksana Ruzhytska
- Department of Internal Medicine n3, Ternopil State Medical University, 46002 Ternopil, Ukraine
| | - Simone Vettoretti
- Nephrology, Dialysis and Renal Transplantation, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Lara Caldiroli
- Nephrology, Dialysis and Renal Transplantation, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Mario Cozzolino
- Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy
- Renal Division, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, 20122 Milan, Italy
| | - Piergiorgio Messa
- Nephrology, Dialysis and Renal Transplantation, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.
- Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy.
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14
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Gembillo G, Cernaro V, Salvo A, Siligato R, Laudani A, Buemi M, Santoro D. Role of Vitamin D Status in Diabetic Patients with Renal Disease. MEDICINA (KAUNAS, LITHUANIA) 2019; 55:273. [PMID: 31200589 PMCID: PMC6630278 DOI: 10.3390/medicina55060273] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/29/2019] [Revised: 06/03/2019] [Accepted: 06/08/2019] [Indexed: 02/07/2023]
Abstract
Diabetes mellitus (DM) poses a major public health problem worldwide, with ever-increasing incidence and prevalence in recent years. The Institute for Alternative Futures (IAF) expects that the total number of people with type 1 and type 2 DM in the United States will increase by 54%, from 19,629,000 to 54,913,000 people, between 2015 and 2030. Diabetic Nephropathy (DN) affects about one-third of patients with DM and currently ranks as the first cause of end-stage kidney disease in the Western world. The complexity of interactions of Vitamin D is directly related with progressive long-term changes implicated in the worsening of renal function. These changes result in a dysregulation of the vitamin D-dependent pathways. Various studies demonstrated a pivotal role of Vitamin D supplementation in regression of albuminuria and glomerulosclerosis, contrasting the increase of glomerular basement membrane thickening and podocyte effacement, with better renal and cardiovascular outcomes. The homeostasis and regulation of the nephron's function are absolutely dependent from the cross-talk between endothelium and podocytes. Even if growing evidence proves that vitamin D may have antiproteinuric, anti-inflammatory and renoprotective effects in patients with DN, it is still worth investigating these aspects with both more in vitro studies and randomized controlled trials in larger patient series and with adequate follow-up to confirm the effects of long-term vitamin D analogue supplementation in DN and to evaluate the effectiveness of this therapy and the appropriate dosage.
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Affiliation(s)
- Guido Gembillo
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria 98,125 Messina, Italy.
| | - Valeria Cernaro
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria 98,125 Messina, Italy.
| | - Antonino Salvo
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria 98,125 Messina, Italy.
| | - Rossella Siligato
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria 98,125 Messina, Italy.
| | - Alfredo Laudani
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria 98,125 Messina, Italy.
| | - Michele Buemi
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria 98,125 Messina, Italy.
| | - Domenico Santoro
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria 98,125 Messina, Italy.
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15
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Cholecalciferol supplementation increases FGF23 in peritoneal dialysis patients with hypovitaminosis D: a randomized clinical trial. J Nephrol 2019; 32:645-659. [DOI: 10.1007/s40620-019-00599-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2018] [Accepted: 03/07/2019] [Indexed: 02/07/2023]
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16
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Dou D, Yang B, Gan H, Xie D, Lei H, Ye N. Vitamin D supplementation for the improvement of vascular function in patients with chronic kidney disease: a meta-analysis of randomized controlled trials. Int Urol Nephrol 2019; 51:851-858. [PMID: 30737643 DOI: 10.1007/s11255-019-02088-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2018] [Accepted: 01/28/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND The efficacy of vitamin D on vascular function remains controversial in chronic kidney disease (CKD) patients. The aim of the present work was to perform a meta-analysis of randomized controlled trials to evaluate the efficacy of vitamin D on vascular function in CKD patients. METHODS We searched Medline, the Cochrane Central Register of Controlled Trials, Embase, the Science Citation Index, and clinical trial registries for randomized controlled trials comparing vitamin D with a placebo in CKD patients. RESULTS We included seven trials. For flow-mediated dilation (FMD), there was no significant difference between the two groups (WMD 1.66%; 95% CI - 0.2 to 3.51, p = 0.08; with significant heterogeneity, p < 0.0001, I2 = 89%). We conducted a subgroup analysis. In the cholecalciferol group, compared with the placebo group, cholecalciferol significantly increased FMD (WMD 5.49%; 95% CI 4.36-6.62, p < 0.0001). In the 2 ug paricalcitol group, compared with the placebo group, paricalcitol significantly increased FMD (WMD 2.09%; 95% CI 1.28-2.9, p < 0.0001; without significant heterogeneity, p = 0.47, I2 = 0%). In the 1 ug paricalcitol group, there was no significant difference between the two groups. For pulse wave velocity (PWV), vitamin D significantly decreased PWV compared with the placebo (WMD - 0.93 m/s; 95% CI - 1.71 to - 0.15, p = 0.02; without significant heterogeneity, p = 0.14, I2 = 45%). For calcium (Ca) and parathyroid hormone (PTH), there was a significant difference between the vitamin D group and the placebo group. For 25-hydroxyvitamin D [25(OH)D], there was a significant difference between the inactive vitamin D group and the placebo group. For phosphorus (P), systolic blood pressure (SBP), and diastolic blood pressure (DBP), there were no significant differences between the two groups. CONCLUSIONS We speculate that vitamin D might be able to improve vascular function in CKD patients. The effect of vitamin D might be associated with its doses and earlier stages of the disease might respond better to vitamin D. Furthermore, trials with larger populations and longer durations are needed in order to provide more reliable evidence.
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Affiliation(s)
- Ding Dou
- Basic Medical College of Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, Sichuan, China.,Traditional Chinese Medical Department of Zunyi Medical and Pharmaceutical College, Zunyi, 563006, Guizhou, China
| | - Bing Yang
- Sichuan 2nd Hospital of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Hongqiao Gan
- Sichuan 2nd Hospital of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Dengpiao Xie
- Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Huangwei Lei
- Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
| | - Naijing Ye
- Sichuan 2nd Hospital of Traditional Chinese Medicine, Chengdu, Sichuan, China. .,Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
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17
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Bellan M, Marzullo P. New Insights on Low Vitamin D Plasma Concentration as a Potential Cardiovascular Risk Factor. Open Rheumatol J 2018. [DOI: 10.2174/1874312901812010261] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
The role of Vitamin D hormone in human health and disease is still debated. Recently, growing attention has been paid to its putative role in cardiovascular system homeostasis with several studies that suggested a correlation between low vitamin D levels and increased cardiovascular risk. Several mechanisms are involved in the development of cardiovascular diseases: systemic inflammation, endothelial dysfunction, arterial hypertension and insulin resistance. In the present paper, we have revised the current literature supporting a role for vitamin D in the development of these pathogenetic processes. Finally, we have evaluated the current evidence linking vitamin D to atherosclerosis and its natural consequence, cardiovascular diseases.
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18
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Kumar V, Yadav AK, Singhal M, Kumar V, Lal A, Banerjee D, Gupta KL, Jha V. Vascular function and cholecalciferol supplementation in CKD: A self-controlled case series. J Steroid Biochem Mol Biol 2018; 180:19-22. [PMID: 29309832 DOI: 10.1016/j.jsbmb.2018.01.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2017] [Revised: 12/26/2017] [Accepted: 01/03/2018] [Indexed: 01/06/2023]
Abstract
Vitamin D deficiency is common and associated with mortality in chronic kidney disease (CKD) patients. Cardiovascular disease (CVD) is the commonest cause of mortality in CKD patients. In a randomized, double blind, placebo controlled trial, we have recently reported favorable effects of vitamin D supplementation on vascular & endothelial function and inflammatory biomarkers in vitamin D deficient patients with non-diabetic stage 3-4 CKD (J Am Soc Nephrol 28: 3100-3108, 2017). Subjects in the placebo group who had still not received vitamin D after completion of the trial received two oral doses 300,000 IU of oral cholecalciferol at 8 weeks interval followed by flow mediated dilatation (FMD), pulse wave velocity (PWV), circulating endothelial and inflammatory markers (E-Selectin, vWF, hsCRP and IL-6), 125 (OH)2D, iPTH and iFGF-23 assessment at 16 weeks. 31 subjects completed this phase of the study. Last values recorded in the preceding clinical trial were taken as baseline values. Serum 25(OH)D and 1,25(OH)2D increased and FMD significantly improved after cholecalciferol supplementation [mean change in FMD%: 5.8% (95% CI: 4.0-7.5%, p < 0.001]. Endothelium independent nitroglycerine mediated dilatation, PWV, iPTH, iFGF-23 and IL-6 also showed favorable changes. The data further cement the findings of beneficial effects of correction of vitamin D deficiency on vascular function.
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Affiliation(s)
- Vivek Kumar
- Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
| | - Ashok Kumar Yadav
- Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Manphool Singhal
- Department of Radiodiagnosis, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Vinod Kumar
- Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Anupam Lal
- Department of Radiodiagnosis, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Debasish Banerjee
- Renal and Transplantation Unit, St. George's University Hospitals National Health Service Foundation Trust, London, UK; Molecular and Clinical Sciences Research Institute, St. George's, University of London, London, UK
| | - Krishan Lal Gupta
- Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Vivekanand Jha
- Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India; George Institute for Global Health, New Delhi, India; George Institute for Global Health, University of Oxford, Oxford, UK
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19
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Vitamin D supplementation improves endothelial dysfunction in patients with non-dialysis chronic kidney disease. Int Urol Nephrol 2018; 50:923-927. [DOI: 10.1007/s11255-018-1829-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2017] [Accepted: 02/17/2018] [Indexed: 10/17/2022]
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20
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Jeong HY, Park KM, Lee MJ, Yang DH, Kim SH, Lee SY. Vitamin D and Hypertension. Electrolyte Blood Press 2017; 15:1-11. [PMID: 29042901 PMCID: PMC5641496 DOI: 10.5049/ebp.2017.15.1.1] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2017] [Accepted: 04/11/2017] [Indexed: 12/11/2022] Open
Abstract
Vitamin D has the pleiotropic effects in multiple organ systems, and vitamin D deficiency was suggested to be associated with high blood pressure according to previous reports. Several interventional studies have examined the effect of vitamin D supplementation on high blood pressure patients, but the results have been inconsistent. In this article, we examined the literature that have proposed a mechanism involving vitamin D in the regulation of blood pressure and review previous observational and interventional studies that have shown the relationship between vitamin D and hypertension among various populations.
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Affiliation(s)
- Hye Yun Jeong
- Division of Nephrology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - Kyung Mi Park
- Division of Nephrology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - Mi Jung Lee
- Division of Nephrology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - Dong Ho Yang
- Division of Nephrology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - Sang Hoon Kim
- Division of Cardiology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - So-Young Lee
- Division of Nephrology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea
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21
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Kumar V, Yadav AK, Lal A, Kumar V, Singhal M, Billot L, Gupta KL, Banerjee D, Jha V. A Randomized Trial of Vitamin D Supplementation on Vascular Function in CKD. J Am Soc Nephrol 2017; 28:3100-3108. [PMID: 28667080 DOI: 10.1681/asn.2017010003] [Citation(s) in RCA: 87] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2017] [Accepted: 05/03/2017] [Indexed: 12/11/2022] Open
Abstract
Vitamin D deficiency associates with mortality in patients with CKD, and vitamin D supplementation might mitigate cardiovascular disease risk in CKD. In this randomized, double-blind, placebo-controlled trial, we investigated the effect of cholecalciferol supplementation on vascular function in 120 patients of either sex, aged 18-70 years, with nondiabetic CKD stage 3-4 and vitamin D deficiency (serum 25-hydroxyvitamin D ≤20 ng/ml). We randomized patients using a 1:1 ratio to receive either two directly observed oral doses of cholecalciferol (300,000 IU) or matching placebo at baseline and 8 weeks. The primary outcome was change in endothelium-dependent brachial artery flow-mediated dilation at 16 weeks. Secondary outcome measures included changes in pulse wave velocity and circulating biomarkers. Cholecalciferol supplementation significantly increased endothelium-dependent brachial artery flow-mediated dilation at 16 weeks, whereas placebo did not (between-group difference in mean change: 5.49%; 95% confidence interval, 4.34% to 6.64%; P<0.001). Intervention also led to significant favorable changes in pulse wave velocity and circulating IL-6 levels. Thus, in nondiabetic patients with stage 3-4 CKD and vitamin D deficiency, vitamin D supplementation may improve vascular function. This study is registered with the Clinical Trials Registry of India (no.: CTRI/2013/05/003648).
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Affiliation(s)
| | | | - Anupam Lal
- Radiodiagnosis, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | | | - Manphool Singhal
- Radiodiagnosis, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Laurent Billot
- George Institute for Global Health, Sydney, New South Wales, Australia.,Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
| | | | - Debasish Banerjee
- Renal and Transplantation Unit, St. George's University Hospitals National Health Service Foundation Trust, London, UK.,Molecular and Clinical Sciences Research Institute, St. George's, University of London, London, UK
| | - Vivekanand Jha
- Departments of Nephrology and .,George Institute for Global Health, New Delhi, India; and.,George Institute for Global Health, University of Oxford, Oxford, UK
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22
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Morrone LF, Bolasco P, Camerini C, Cianciolo G, Cupisti A, Galassi A, Mazzaferro S, Russo D, Russo L, Cozzolino M. Vitamin D in patients with chronic kidney disease: a position statement of the Working Group "Trace Elements and Mineral Metabolism" of the Italian Society of Nephrology. J Nephrol 2016; 29:305-328. [PMID: 27062486 DOI: 10.1007/s40620-016-0305-6] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2016] [Accepted: 03/30/2016] [Indexed: 02/07/2023]
Abstract
In the late 1970s, calcitriol was introduced into clinical practice for the management of secondary renal hyperparathyroidism in chronic kidney disease (CKD). Since then, the use of calcifediol or other native forms of vitamin D was largely ignored until the publication of the 2009 Kidney Disease Improving Global Outcomes (KDIGO) recommendations. The guidelines suggested that measurement of circulating levels of 25(OH)D (calcifediol) and its supplementation were to be performed on the same basis as for the general population. This indication was based on the fact that the precursors of active vitamin D had provided to CKD patients considerable benefits in survival, mainly due to their pleiotropic effects on the cardiovascular system. However, despite the long-term use of various classes of vitamin D in CKD, a clear definition is still lacking concerning the most appropriate time for initiation of therapy, the best compound to prescribe (active metabolites or analogs), the proper dosage, and the most suitable duration of therapy. The aim of this position statement is to provide and critically appraise the current plentiful evidence on vitamin D in different clinical settings related to CKD, particularly focusing on outcomes, monitoring and treatment-associated risks. However, it should be taken in account that position statements are meant to provide guidance; therefore, they are not to be considered prescriptive for all patients and, importantly, they cannot replace the judgment of clinicians.
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Affiliation(s)
- Luigi Francesco Morrone
- Nephrology, Dialysis and Renal Transplantation Unit, University Hospital "Policlinico", Bari, Italy.
| | - Pergiorgio Bolasco
- Territorial Unit of Nephrology and Dialysis-ASL 8 of Cagliari, Cagliari, Italy
| | - Corrado Camerini
- Operative Unit of Nephrology, AO Spedali Civili di Brescia and University of Brescia, Brescia, Italy
| | - Giuseppe Cianciolo
- Nephrology Dialysis and Renal Transplantation Unit, S. Orsola University Hospital, Bologna, Italy
| | - Adamasco Cupisti
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | | | - Sandro Mazzaferro
- Department of Cardiovascular Respiratory Nephrologic Anesthetic and Geriatric Sciences, Sapienza University of Rome, Rome, Italy
| | - Domenico Russo
- Department of Public Health, Unit of Nephrology and Hypertension, University of Naples Federico II, Naples, Italy
| | - Luigi Russo
- Department of Public Health, Unit of Nephrology and Hypertension, University of Naples Federico II, Naples, Italy
| | - Mario Cozzolino
- Renal Division and Laboratory of Experimental Nephrology, Department of Health Sciences, San Paolo Hospital, University of Milan, Milan, Italy
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Husain K, Suarez E, Isidro A, Hernandez W, Ferder L. Effect of paricalcitol and enalapril on renal inflammation/oxidative stress in atherosclerosis. World J Biol Chem 2015; 6:240-248. [PMID: 26322179 PMCID: PMC4549765 DOI: 10.4331/wjbc.v6.i3.240] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2015] [Revised: 03/25/2015] [Accepted: 06/11/2015] [Indexed: 02/05/2023] Open
Abstract
AIM: To investigate the protective effect of paricalcitol and enalapril on renal inflammation and oxidative stress in ApoE-knock out mice.
METHODS: Animals treated for 4 mo as group (1) ApoE-knock out plus vehicle, group (2) ApoE-knock out plus paricalcitol (200 ng thrice a week), (3) ApoE-knock out plus enalapril (30 mg/L), (4) ApoE-knock out plus paricalcitol plus enalapril and (5) normal. Blood pressure (BP) was recorded using tail cuff method. The kidneys were isolated for biochemical assays using spectrophotometer and Western blot analyses.
RESULTS: ApoE-deficient mice developed high BP (127 ± 3 mmHg) and it was ameliorated by enalapril and enalapril plus paricalcitol treatments but not with paricalcitol alone. Renal malondialdehyde concentrations, p22phox, manganese-superoxide dismutase, inducible nitric oxide synthase (NOS), monocyte chemoattractant protein-1, tumor necrosis factor-alpha and transforming growth factor-β1 levels significantly elevated but reduced glutathione, CuZn-SOD and eNOS levels significantly depleted in ApoE-knock out animals compared to normal. Administration of paricalcitol, enalapril and combined together ameliorated the renal inflammation and oxidative stress in ApoE-knock out animals.
CONCLUSION: Paricalcitol and enalapril combo treatment ameliorates renal inflammation as well as oxidative stress in atherosclerotic animals.
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