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Jørgensen HS, Vervloet M, Cavalier E, Bacchetta J, de Borst MH, Bover J, Cozzolino M, Ferreira AC, Hansen D, Herrmann M, de Jongh R, Mazzaferro S, Wan M, Shroff R, Evenepoel P. The role of nutritional vitamin D in chronic kidney disease-mineral and bone disorder in children and adults with chronic kidney disease, on dialysis, and after kidney transplantation-a European consensus statement. Nephrol Dial Transplant 2025; 40:797-822. [PMID: 39875204 PMCID: PMC11960744 DOI: 10.1093/ndt/gfae293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Indexed: 01/30/2025] Open
Abstract
Vitamin D deficiency is common in patients with chronic kidney disease (CKD) and associates with poor outcomes. Current clinical practice guidelines recommend supplementation with nutritional vitamin D as for the general population. However, recent large-scale clinical trials in the general population failed to demonstrate a benefit of vitamin D supplementation on skeletal or non-skeletal outcomes, fueling a debate on the rationale for screening for and correcting vitamin D deficiency, both in non-CKD and CKD populations. In a collaboration between the European Renal Osteodystrophy initiative of the European Renal Association (ERA) and the European Society for Paediatric Nephrology (ESPN), an expert panel performed an extensive literature review and formulated clinical practice points on vitamin D supplementation in children and adults with CKD and after kidney transplantation. These were reviewed by a Delphi panel of members from relevant working groups of the ERA and ESPN. Key clinical practice points include recommendations to monitor for, and correct, vitamin D deficiency in children and adults with CKD and after kidney transplantation, targeting 25-hydroxyvitamin D levels >75 nmol/l (>30 ng/ml). Although vitamin D supplementation appears well-tolerated and safe, it is recommended to avoid mega-doses (≥100 000 IU) and very high levels of 25 hydroxyvitamin D (>150-200 nmol/l, or 60-80 ng/ml) to reduce the risk of toxicity. Future clinical trials should investigate the benefit of vitamin D supplementation on patient-relevant outcomes in the setting of vitamin D deficiency across different stages of CKD.
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Affiliation(s)
- Hanne Skou Jørgensen
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Department of Nephrology, Aalborg University Hospital, Aalborg, Denmark
| | - Marc Vervloet
- Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Etienne Cavalier
- Department of Clinical Chemistry, CIRM, University of Liege, CHU de Liège, Liège, Belgium
| | - Justine Bacchetta
- Department of Pediatric Nephrology, Reference Center for Rare Diseases of Calcium and Phosphate, INSERM1033 Research Unit, Hospices Civils de Lyon, Université Lyon 1, Lyon, France
| | - Martin H de Borst
- Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Jordi Bover
- Department of Nephrology, University Hospital Germans Trias i Pujol, Badalona (Barcelona), Catalonià, Spain
| | - Mario Cozzolino
- Department of Health Sciences, Renal Division, University of Milan, Milan, Italy
| | - Ana Carina Ferreira
- Nephrology Department, Hospital Curry Cabral | ULS São José, Lisbon, Portugal and Nova Medical School, Lisbon, Portugal
| | - Ditte Hansen
- Department of Nephrology, Copenhagen University Hospital-Herlev, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Markus Herrmann
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
| | - Renate de Jongh
- Department of Endocrinology and Metabolism, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Sandro Mazzaferro
- Department of Translation and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Mandy Wan
- Institute of Pharmaceutical Science, King's College London, London, UK and Department of Evelina Pharmacy, Guys' & St Thomas' NHS Foundation Trust, London, UK
| | - Rukshana Shroff
- Renal Unit, UCL Great Ormond Street Hospital for Children; University College London, London, UK
| | - Pieter Evenepoel
- Department of Microbiology, Immunology and Transplantation; Nephrology and Renal Transplantation Research Group, KU Leuven, Leuven, Belgium
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Salera D, Merkel N, Bellasi A, de Borst MH. Pathophysiology of chronic kidney disease-mineral bone disorder (CKD-MBD): from adaptive to maladaptive mineral homeostasis. Clin Kidney J 2025; 18:i3-i14. [PMID: 40083952 PMCID: PMC11903091 DOI: 10.1093/ckj/sfae431] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Indexed: 03/16/2025] Open
Abstract
Chronic kidney disease-mineral bone disorder (CKD-MBD) is a multifaceted condition commonly seen in people with reduced kidney function. It involves a range of interconnected issues in mineral metabolism, bone health and cardiovascular calcification, which are linked to a lower quality of life and shorter life expectancy. Although various epidemiological studies show that the laboratory changes defining CKD-MBD become more common as the glomerular filtration rate declines, the pathophysiology of CKD-MBD is still largely unexplained. We herein review the current understanding of CKD-MBD, provide a conceptual framework to understand this syndrome, and review the genetic and environmental factors that may influence the clinical manifestation of CKD-MBD. However, a deeper understanding of the pathophysiology of CKD-MBD is needed to understand the phenotype variability and the relative contribution to organ damage of factors involved in CKD-MBD to develop more effective interventions to improve outcomes in patients with CKD.
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Affiliation(s)
- Davide Salera
- Service of Nephrology, Ospedale Regionale di Lugano, Ospedale Civico, Ente Ospedaliero Cantonale, Lugano, Switzerland
| | - Nathalie Merkel
- Service of Nephrology, Ospedale Regionale di Lugano, Ospedale Civico, Ente Ospedaliero Cantonale, Lugano, Switzerland
| | - Antonio Bellasi
- Service of Nephrology, Ospedale Regionale di Lugano, Ospedale Civico, Ente Ospedaliero Cantonale, Lugano, Switzerland
- Università della Svizzera italiana (USi), Faculty of Biomedical Sciences, Lugano, Switzerland
| | - Martin H de Borst
- Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
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Atik Ö, Tepetam FM, Özden Ş, Can A, Şaylan B. Desensitization to colecalciferol in 18 patients with immediate hypersensitivity reactions. World Allergy Organ J 2025; 18:101029. [PMID: 40034581 PMCID: PMC11873155 DOI: 10.1016/j.waojou.2025.101029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 01/10/2025] [Accepted: 01/13/2025] [Indexed: 03/05/2025] Open
Abstract
Introduction Hypersensitivity reactions (HSRs) to colecalciferol (vitamin D) have been rarely reported and the mechanism is unknown. As an alternative treatment was not recommended for vitamin D deficiency, a desensitization protocol with colecalciferol can be performed. We found that there is no standard desensitization protocol for vitamin D. In this study, we aimed to investigate clinical features and skin test results of patients with HSRs to the vitamin D and effectiveness of the 6-step desensitization protocol in which we applied oral drops of colecalciferol. Method This retrospective cross-sectional study included 18 patients with a history of HSRs to oral vitamin D supplements and patients who were planned to receive oral vitamin D replacement. Before desensitization, some of the patients underwent skin tests (skin prick test and intradermal test) with colecalciferol, and the results were recorded. Skin tests were not performed in patients with a history of drug use (antihistamine, systemic steroid, omalizumab, etc.) that affected the results of skin tests. All patients were applied an one bag 6-step desensitization protocol with colecalciferol. Vitamin D3 solution was administered totally 30 drop (4000 IU)/day (1 drop:133.33 IU of 3333 IU/mL) dose of colecalciferol (Devit-3®, DEVA-Türkiye, 15 mL/50,000 IU, 1 mL = 25 drop) at 15-minutes intervals without premedication. Results The patient group consisted of 16 female subjects (89%); the mean age was 46 ± 12 years. When the patients were evaluated in terms of the risk of hypersensitivity reactions according to their clinical history, 5 patients had a history of anaphylaxis with vitamin D preparations (colecalciferol oral drop, n = 3; colecalciferol capsule, n = 2), and 13 patients had a history of HSRs other than anaphylaxis with isolated cutaneous reactions (pruritus, flushing, urticaria and angioedema) (n = 11, colecalciferol oral drop; n = 2, colecalciferol capsule). Skin prick test (SPT) and intradermal test (IDT) were performed on 9 patients. SPTs and IDTs were negative in all patients. Urticaria occur during desensitization in only one patient but vitamin D replacement was performed within the following 48-72 h after HSRs. All other patients tolerated 30 drop (4000 IU) and have continued to take same dose every day for the last 6 weeks with no adverse reactions. Conclusion Desensitization with oral vitamin D preparations has a crucial role for patients who can not receive vitamin D supplements by other ways. Vitamin D drop forms, which are better absorbed than capsule forms which contains the lowest units per/mL without the need to dilute the preparation, not contain any additives with HSRs potential such as gelatin and peanut oil are good option. Our 6-step desensitization protocol with oral drop of colecalciferol is a reliable protocol in patients with a history of vitamin D HSRs.
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Affiliation(s)
- Özge Atik
- University of Health Sciences, Süreyyapasa Chest Diseases and Thoracic Surgery Training and Research Hospital, Department of Immunology and Allergy, İstanbul, Turkey
| | - Fatma Merve Tepetam
- University of Health Sciences, Süreyyapasa Chest Diseases and Thoracic Surgery Training and Research Hospital, Department of Immunology and Allergy, İstanbul, Turkey
| | - Şeyma Özden
- University of Health Sciences, Süreyyapasa Chest Diseases and Thoracic Surgery Training and Research Hospital, Department of Immunology and Allergy, İstanbul, Turkey
| | - Ali Can
- University of Health Sciences, Van Training and Research Hospital, Department of Immunology and Allergy, Van, Turkey
| | - Bengü Şaylan
- University of Health Sciences Süreyyapaşa Chest Diseases and Thoracic Surgery Training and Research Hospital, Chest Diseases Clinic, Istanbul, Turkey
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Chen Y, Chen D, Peng Y, Wang M, Wang W, Shi F, Wang Y, Hua L. The effect of vitamin D supplementation on endothelial function: An umbrella review of interventional meta-analyses. Nutr Metab Cardiovasc Dis 2025:103871. [PMID: 39986938 DOI: 10.1016/j.numecd.2025.103871] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 12/10/2024] [Accepted: 01/22/2025] [Indexed: 02/24/2025]
Abstract
AIMS There is no consensus in the existing literature regarding the effect of vitamin D supplementation on endothelial function. This umbrella review aimed to assess meta-analyses of randomized controlled trials (RCTs) conducted in this field. DATA SYNTHESIS We systematically searched English-language databases, including PubMed, Embase, Scopus, and Web of Science, up to January 2024. Flow-Mediated Dilation (FMD), Pulse Wave Velocity (PWV), and Augmentation Index (AIx) were the primary endpoints evaluated. A total of 16 meta-analyses were included in the review. The results indicated that vitamin D supplementation significantly improved FMD as assessed by Standardized Mean Difference (SMD) (SMD = 0.72, 95 % CI: 0.34, 1.11; p < 0.001; I2 = 79.4 %, p < 0.001) and Weighted Mean Difference (WMD) (WMD = 1.91; 95 % CI: 0.66, 3.16; p = 0.003; I2 = 94.5 %, p < 0.001). PWV also showed a modest but significant improvement (SMD = -0.06, 95 % CI: -0.12, -0.00; p = 0.03; I2 = 0.0 %, p = 0.66). However, vitamin D had no significant impact on AIx based on SMD (SMD = -0.03, 95 % CI: -0.13, 0.06; p = 0.48; I2 = 0.0 %, p = 0.49) or WMD (WMD = 0.02, 95 % CI: -2.22, 2.25; p = 0.98; I2 = 29.2 %, p = 0.23). CONCLUSION These findings suggest that vitamin D supplementation may be a beneficial intervention for improving endothelial function, particularly in populations with low FMD. The effects on PWV were modest, while AIx remained unaffected. REGISTRATION NUMBER PROSPERO, CRD42024451215.
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Affiliation(s)
- Yirui Chen
- Cancer Center, Department of Hematology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, 58 Shangtang Road, Hangzhou, Zhejiang, 310014, PR China
| | - Dandan Chen
- Cancer Center, Department of Hematology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, 58 Shangtang Road, Hangzhou, Zhejiang, 310014, PR China
| | - Ye Peng
- Cancer Center, Department of Hematology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, 58 Shangtang Road, Hangzhou, Zhejiang, 310014, PR China
| | - Manling Wang
- Cancer Center, Department of Hematology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, 58 Shangtang Road, Hangzhou, Zhejiang, 310014, PR China
| | - Wensong Wang
- Cancer Center, Department of Hematology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, 58 Shangtang Road, Hangzhou, Zhejiang, 310014, PR China
| | - Fangfang Shi
- Cancer Center, Department of Hematology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, 58 Shangtang Road, Hangzhou, Zhejiang, 310014, PR China
| | - Yanzhong Wang
- Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, Zhejiang, 310016, PR China.
| | - Liqun Hua
- Cancer Center, Department of Hematology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, 58 Shangtang Road, Hangzhou, Zhejiang, 310014, PR China.
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Rivero A, Wehmeier KR, Haas MJ, Mooradian AD. Vitamin D, immune function, and atherosclerosis. Where are we now? Nutr Res 2025; 133:148-160. [PMID: 39733509 DOI: 10.1016/j.nutres.2024.07.007] [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: 05/30/2023] [Revised: 07/22/2024] [Accepted: 07/23/2024] [Indexed: 12/31/2024]
Abstract
The role of vitamin D in regulating calcium metabolism and skeletal growth and disease is widely recognized. Indeed, current recommendations for serum vitamin D concentrations are based on these parameters. A serum vitamin D <20 ng/mL is considered deficient, concentrations between 20 and 30 ng/mL are insufficient, and >30 ng/mL is adequate. However, over the past number of years, epidemiological studies, randomized clinical trials, and preclinical animal and cell culture-based research have demonstrated that vitamin D modulates immune function. Cardiovascular disease (CVD), the leading cause of morbidity and mortality in the United States and in industrialized nations, is mediated in part by chronic inflammation as well as by other well-established risk factors including dyslipidemia, hypertension, obesity, and diabetes. Vitamin D deficiency (<20 ng/mL or <50 nM) is associated with increased CVD risk. As described in this review, several recent systematic reviews and meta-analyses provide some evidence that vitamin D administration to individuals with vitamin D deficiency may have little effect on CVD-related mortality. Many well-designed randomized clinical trials in the general population as well as in people at risk for CVD-related complication later in life provide evidence that treatment may be beneficial. These latter studies as well as the paucity of information regarding the optimal vitamin D concentration required for optimizing immune function in patients indicate that more research is needed to address whether vitamin D supplements may be a cost-effective intervention for preventing CVD.
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Affiliation(s)
- Ailyn Rivero
- Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Florida College of Medicine, Jacksonville, FL 32206
| | - Kent R Wehmeier
- Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Florida College of Medicine, Jacksonville, FL 32206
| | - Michael J Haas
- Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Florida College of Medicine, Jacksonville, FL 32206.
| | - Arshag D Mooradian
- Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Florida College of Medicine, Jacksonville, FL 32206
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Ristic-Medic D, Takic M, Pokimica B, Terzic B, Kojadinovic M, Lepic T, Radjen S, Vucic V. Dietary Omega-3 PUFA Intake in Patients with Chronic Kidney Disease: The Association with Vitamin D Deficiency, Intima-Media Thickness and Blood Pressure. J Clin Med 2024; 13:5593. [PMID: 39337080 PMCID: PMC11432386 DOI: 10.3390/jcm13185593] [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: 08/29/2024] [Revised: 09/11/2024] [Accepted: 09/18/2024] [Indexed: 09/30/2024] Open
Abstract
Background/Objectives: Numerous risk factors associated with development of cardiovascular disease (CVD) have been unfavorably altered in patients with chronic kidney disease (CKD). Low omega-3 polyunsaturated fatty acid (PUFA) intake and vitamin D deficiency are potential cardiometabolic risk factors in patients with CKD. The aim of this study was to evaluate dietary intake and status of omega-3 PUFA and vitamin D in pre-dialysis and hemodialysis patients and to examine the association of dietary α-linolenic acid (ALA) and fish consumption with blood pressure and carotid intima-media thickness (C-IMT), representing a non-invasive marker of atherosclerosis in CKD patients. Methods: All 77 selected patients (36 pre-dialysis, 41 on hemodialysis) underwent standardized clinical, nutritional, and laboratory assessments. Repeated 24 h recalls were performed to assess dietary intake. The fatty acid profile was determined by gas-liquid chromatography. Results: Inadequate vitamin D intake and vitamin D status were found in 95% of patients. PUFA profiles did not differ between hemodialysis and pre-dialysis participants. Dietary intake of ALA was negatively correlated with systolic blood pressure (SBP) (p = 0.013), C-IMT (p = 0.002), serum CRP (p = 0.044), iPTH (p = 0.01), and 25(OH)D3 (p = 0.006). ALA intake of more than 0.23 g daily was linked with lower SBP (p = 0.001), serum 25(OH)D3 (p = 0.004), and C-IMT (p = 0.002). Conclusions: This study contributes to a better understanding of the relationship between dietary ALA intake and C-IMT in CKD. The results of this study could emphasize the significant role of the high prevalence of vitamin D deficiency and inadequate omega-3 PUFA intake and status regarding CVD health in CKD patients.
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Affiliation(s)
- Danijela Ristic-Medic
- Group for Nutritional Biochemistry and Dietology, Centre of Research Excellence in Nutrition and Metabolism, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11129 Belgrade, Serbia
| | - Marija Takic
- Group for Nutrition and Metabolism, Centre of Research Excellence in Nutrition and Metabolism, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11129 Belgrade, Serbia
| | - Biljana Pokimica
- Group for Nutritional Biochemistry and Dietology, Centre of Research Excellence in Nutrition and Metabolism, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11129 Belgrade, Serbia
| | - Brankica Terzic
- Clinic of Nephrology, Military Medical Academy, Faculty of Medicine, University of Defense, 11040 Belgrade, Serbia
| | - Milica Kojadinovic
- Group for Nutritional Biochemistry and Dietology, Centre of Research Excellence in Nutrition and Metabolism, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11129 Belgrade, Serbia
| | - Toplica Lepic
- Clinic of Neurology, Military Medical Academy, Faculty of Medicine, University of Defense, 11040 Belgrade, Serbia
| | - Slavica Radjen
- Institute of Hygiene, Military Medical Academy, Faculty of Medicine, University of Defense, 11040 Belgrade, Serbia
| | - Vesna Vucic
- Group for Nutritional Biochemistry and Dietology, Centre of Research Excellence in Nutrition and Metabolism, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11129 Belgrade, Serbia
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Lin TC, Lin SW, Yeh KT. Parathyroidectomy restored bone mineral density in a neglected femoral neck fracture with renal osteodystrophy: A case report. World J Clin Cases 2024; 12:5761-5768. [PMID: 39247751 PMCID: PMC11263049 DOI: 10.12998/wjcc.v12.i25.5761] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Revised: 06/11/2024] [Accepted: 07/03/2024] [Indexed: 07/12/2024] Open
Abstract
BACKGROUND This case report contributes to the medical literature by highlighting the successful management of a neglected femoral neck fracture in a patient with renal osteodystrophy and secondary hyperparathyroidism (SHPTH) who was on dialysis due to end-stage renal disease (ESRD). It underscores the efficacy of parathyroidectomy (PTX) in restoring bone mineral density (BMD) and promoting fracture healing, addressing a significant complication in ESRD patients. CASE SUMMARY A 36-year-old female with renal osteodystrophy and on dialysis due to ESRD presented with a history of left patellar tendon rupture and later, a right achilles tendon avulsion fracture. Persistent right hip pain led to the discovery of a neglected right femoral neck fracture, which was initially overlooked due to the patient's complex medical history. Two months post-achilles tendon repair, the patient underwent PTX to manage the refractory SHPTH. The postoperative course included rehabilitation and weight-bearing exercises. Remarkably, 2 years after osteosynthesis, radiographic assessments indicated a solid union of the periprothesis fracture and significant improvement in BMD, showcasing the efficacy of the treatment approach. CONCLUSION PTX, combined with appropriate rehabilitation, is crucial for improving BMD and fracture healing in ESRD patients with SHPTH.
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Affiliation(s)
- Tzu-Ching Lin
- Department of Education, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970473, Taiwan Province, China
| | - Shih-Wei Lin
- Department of Orthopedics, Ten-Chan Medical Group, Taoyuan 320003, Taiwan Province, China
| | - Kuang-Ting Yeh
- Department of Education, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970473, Taiwan Province, China
- Department of Orthopedics, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970473, Taiwan Province, China
- Department of Graduate Institute of Clinical Pharmacy, Tzu Chi University, Hualien 970374, Taiwan Province, China
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Lapauw B, Laurent MR, Rozenberg S, Body JJ, Bruyère O, Gielen E, Goemaere S, Iconaru L, Cavalier E. When and How to Evaluate Vitamin D Status? A Viewpoint from the Belgian Bone Club. Nutrients 2024; 16:2388. [PMID: 39125269 PMCID: PMC11313844 DOI: 10.3390/nu16152388] [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: 06/10/2024] [Revised: 07/09/2024] [Accepted: 07/11/2024] [Indexed: 08/12/2024] Open
Abstract
Low serum vitamin D levels have been associated with a variety of health conditions which has led the medical community but also the general population to evaluate vitamin D status quite liberally. Nevertheless, there remain questions about the efficacy and cost-effectiveness of such a broad and untargeted approach. This review therefore aims to summarize the current evidence and recommendations on when and how to evaluate vitamin D status in human health and disease. For the general population, most guidelines do not recommend universal screening but suggest a targeted approach in populations at risk. Also, some guidelines do not even recommend evaluating vitamin D status when vitamin D substitution is indicated anyway, such as in children or patients receiving anti-osteoporosis drugs. In those guidelines that recommend the screening of vitamin D status, serum 25(OH)D levels are universally proposed as the preferred screening tool. However, little attention is given to analytical considerations and almost no guidelines discuss the timing and frequency of screening. Finally, there is the known variability in diagnostic thresholds for defining vitamin D insufficiency and deficiency. Overall, the existing guidelines on the evaluation of vitamin D status differ broadly in screening strategy and screening implementation, and none of these guidelines discusses alternative screening modes, for instance, the vitamin metabolic ratio. Efforts to harmonize these different guidelines are needed to enhance their efficacy and cost-effectiveness.
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Affiliation(s)
- Bruno Lapauw
- Department of Endocrinology, Unit for Osteoporosis and Metabolic Bone Diseases, Ghent University Hospital, 9052 Ghent, Belgium;
- Department of Internal Medicine and Pediatrics, Ghent University, 9052 Ghent, Belgium
| | - Michaël R. Laurent
- Geriatrics Department, Imelda Hospital, 2820 Bonheiden, Belgium
- Centre for Metabolic Bone Diseases, University Hospitals Leuven, 3000 Leuven, Belgium;
| | - Serge Rozenberg
- Department of Obstetrics and Gynecology, CHU St Pierre, Brussels & Université Libre de Bruxelles, 1000 Bruxelles, Belgium;
| | - Jean-Jacques Body
- Department of Medicine, CHU Brugmann, Université Libre de Bruxelles, 1020 Brussels, Belgium; (J.-J.B.); (L.I.)
| | - Olivier Bruyère
- WHO Collaborating Center for Public Health Aspects of Musculoskeletal Health and Ageing, Research Unit in Public Health, Epidemiology and Health Economics, Department of Sport and Rehabilitation Sciences, University of Liège, 4000 Liège, Belgium;
| | - Evelien Gielen
- Centre for Metabolic Bone Diseases, University Hospitals Leuven, 3000 Leuven, Belgium;
- Geriatrics & Gerontology, Department of Public Health and Primary Care, KU Leuven, 3000 Leuven, Belgium
- Department of Geriatric Medicine, University Hospitals Leuven, 3000 Leuven, Belgium
| | - Stefan Goemaere
- Department of Endocrinology, Unit for Osteoporosis and Metabolic Bone Diseases, Ghent University Hospital, 9052 Ghent, Belgium;
- Department of Internal Medicine and Pediatrics, Ghent University, 9052 Ghent, Belgium
| | - Laura Iconaru
- Department of Medicine, CHU Brugmann, Université Libre de Bruxelles, 1020 Brussels, Belgium; (J.-J.B.); (L.I.)
| | - Etienne Cavalier
- Department of Clinical Chemistry, University of Liège, CIRM, CHU de Liège, 4000 Liège, Belgium;
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Bello N, Hudu SA, Alshrari AS, Imam MU, Jimoh AO. Overview of Hepatitis B Vaccine Non-Response and Associated B Cell Amnesia: A Scoping Review. Pathogens 2024; 13:554. [PMID: 39057781 PMCID: PMC11279426 DOI: 10.3390/pathogens13070554] [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: 05/24/2024] [Revised: 06/18/2024] [Accepted: 06/19/2024] [Indexed: 07/28/2024] Open
Abstract
BACKGROUND The advent of the hepatitis B vaccine has achieved tremendous success in eradicating and reducing the burden of hepatitis B infection, which is the main culprit for hepatocellular carcinoma-one of the most fatal malignancies globally. Response to the vaccine is achieved in about 90-95% of healthy individuals and up to only 50% in immunocompromised patients. This review aimed to provide an overview of hepatitis B vaccine non-response, the mechanisms involved, B cell amnesia, and strategies to overcome it. METHODS Databases, including Google Scholar, PubMed, Scopus, Cochrane, and ClinicalTrials.org, were used to search and retrieve articles using keywords on hepatitis B vaccine non-response and B cell amnesia. The PRISMA guideline was followed in identifying studies, screening, selection, and reporting of findings. RESULTS A total of 133 studies on hepatitis B vaccine non-response, mechanisms, and prevention/management strategies were included in the review after screening and final selection. Factors responsible for hepatitis B vaccine non-response were found to include genetic, immunological factors, and B cell amnesia in healthy individuals. The genetic factors were sex, HLA haplotypes, and genetic polymorphisms in immune response markers (cytokines). Non-response was common in conditions of immunodeficiency, such as renal failure, haemodialysis, celiac disease, inflammatory bowel disease, hepatitis C co-infection, and latent hepatitis B infection. Others included diabetes mellitus and HIV infection. The mechanisms involved were impaired immune response by suppression of response (T helper cells) or induced suppression of response (through regulatory B and T cells). DISCUSSION A comprehensive and careful understanding of the patient factors and the nature of the vaccine contributes to developing effective preventive measures. These include revaccination or booster dose, vaccine administration through the intradermal route, and the use of adjuvants in the vaccine.
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Affiliation(s)
- Nura Bello
- Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto 840232, Nigeria;
- Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Ahmadu Bello University, Zaria 810107, Nigeria
| | - Shuaibu A. Hudu
- Department of Basic Medical and Dental Sciences, Faculty of Dentistry, Zarqa University, Zarqa 13110, Jordan
- Department of Medical Microbiology and Parasitology, Faculty of Basic Clinical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto 840232, Nigeria
| | - Ahmed S. Alshrari
- Medical Laboratory Technology Department, Faculty of Applied Medical Science, Northern Border University, Arar 91431, Saudi Arabia;
| | - Mustapha U. Imam
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, Sokoto 840232, Nigeria;
| | - Abdulgafar O. Jimoh
- Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto 840232, Nigeria;
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10
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Nguyen LHT, Dang AK, Nguyen GT, Tran AM, Nguyen TT, Duong PT, Vu HN, Le HT. A practical approach to nutritional intervention for people with chronic kidney disease in Vietnam. Asia Pac J Clin Nutr 2024; 33:176-183. [PMID: 38794977 PMCID: PMC11170003 DOI: 10.6133/apjcn.202406_33(2).0004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 03/07/2024] [Accepted: 05/20/2024] [Indexed: 05/27/2024]
Abstract
BACKGROUND AND OBJECTIVES A comprehensive nutritional management is necessary for favourable outcomes in patients with chronic kidney disease (CKD). We aimed to assess the changes in nutritional status and disease progression with nutritional management where renal replacement therapy (RRT) was not in place. METHODS AND STUDY DESIGN A quasi-experiment intervention was conducted on 70 CKD patients at stages 3-5 from July to December 2022. Participants were excluded if they underwent RRT, including dialy-sis (hemodialysis or peritoneal dialysis), or kidney transplantation. The nutritional regimen covered nutrition-al counseling, samples of the dietary menu, and supplement products. We evaluated nutritional status using Subjective Global Assessment (SGA) scale and sub-clinical blood test at T0 (hospital admission) and T1 (two weeks after the admission or 24 hours before the discharge). RESULTS After the intervention, the number of patients classified as malnutrition or at risk of malnourished reduced significantly (65.7% to 54.3% and 25.7% and 5.7%, respectively). The serum concentration of urea, creatinine and parathyroid hormone decreased remarkably, especially in patients receiving nutritional management. In the intervention group, the dietary pattern provided increased intakes of calcium and iron at T1, while phosphorus, sodium and potassium decreased after follow-up. Nausea/vomiting, loss of appetite, tiredness and sleep disorders were improved in the intervention compared to the control group. CONCLUSIONS Nutritional therapy enhanced the nutritional sta-tus, and quality of dietary and renal function in CKD patients without RRT. Applying nutrition education and treatment at an early stage can slow CKD progression, which should be applicable elsewhere in Vietnam.
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Affiliation(s)
- Lan Huong Thi Nguyen
- School of Preventive Medicine and Public Health, Hanoi Medical University, Hanoi, Vietnam
- Department of Nutrition, Saint Paul General Hospital, Hanoi, Vietnam
| | - Anh Kim Dang
- School of Preventive Medicine and Public Health, Hanoi Medical University, Hanoi, Vietnam.
- Queensland Alliance for Environmental Health Sciences (QAEHS), The University of Queensland, Brisbane, Australia
| | - Giang Thu Nguyen
- Population Health Sciences Institute, Faculty of Medical Science, Newcastle University, UK
| | | | | | - Phuong Thi Duong
- Department of Nutrition and Dietetics, Hanoi Medical University Hospital, Hanoi, Vietnam
| | - Ha Ngoc Vu
- Department of Nutrition and Dietetics, Hanoi Medical University Hospital, Hanoi, Vietnam
| | - Huong Thi Le
- School of Preventive Medicine and Public Health, Hanoi Medical University, Hanoi, Vietnam
- Department of Nutrition and Dietetics, Hanoi Medical University Hospital, Hanoi, Vietnam
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11
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Christodoulou M, Aspray TJ, Piec I, Fraser WD, Schoenmakers I. Alterations in regulators of the renal-bone axis, inflammation and iron status in older people with early renal impairment and the effect of vitamin D supplementation. Age Ageing 2024; 53:afae096. [PMID: 38770543 PMCID: PMC11106582 DOI: 10.1093/ageing/afae096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 03/21/2024] [Indexed: 05/22/2024] Open
Abstract
CONTEXT Chronic kidney disease (CKD) leads to alterations in fibroblast growth factor 23 (FGF23) and the renal-bone axis. This may be partly driven by altered inflammation and iron status. Vitamin D supplementation may reduce inflammation. OBJECTIVE AND METHODS Older adults with early CKD (estimated glomerular filtration rate (eGFR) 30-60 ml/min/1.73 m2; CKDG3a/b; n = 35) or normal renal function (eGFR >90 ml/min/1.73 m2; CKDG1; n = 35) received 12,000, 24,000 or 48,000 IU D3/month for 1 year. Markers of the renal-bone axis, inflammation and iron status were investigated pre- and post-supplementation. Predictors of c-terminal and intact FGF23 (cFGF23; iFGF23) were identified by univariate and multivariate regression. RESULTS Pre-supplementation, comparing CKDG3a/b to CKDG1, plasma cFGF23, iFGF23, PTH, sclerostin and TNFα were significantly higher and Klotho, 1,25-dihydroxyvitamin D and iron were lower. Post-supplementation, only cFGF23, 25(OH)D and IL6 differed between groups. The response to supplementation differed between eGFR groups. Only in the CKDG1 group, phosphate decreased, cFGF23, iFGF23 and procollagen type I N-propeptide increased. In the CKDG3a/b group, TNFα significantly decreased, and iron increased. Plasma 25(OH)D and IL10 increased, and carboxy-terminal collagen crosslinks decreased in both groups. In univariate models cFGF23 and iFGF23 were predicted by eGFR and regulators of calcium and phosphate metabolism at both time points; IL6 predicted cFGF23 (post-supplementation) and iFGF23 (pre-supplementation) in univariate models. Hepcidin predicted post-supplementation cFGF23 in multivariate models with eGFR. CONCLUSION Alterations in regulators of the renal-bone axis, inflammation and iron status were found in early CKD. The response to vitamin D3 supplementation differed between eGFR groups. Plasma IL6 predicted both cFGF23 and iFGF23 and hepcidin predicted cFGF23.
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Affiliation(s)
| | - Terence J Aspray
- Freeman Hospital, Bone Clinic, University of Newcastle upon Tyne, Newcastle upon Tyne, UK
| | - Isabelle Piec
- University of East Anglia, Norwich Medical School, Norwich, UK
| | - William D Fraser
- University of East Anglia, Norwich Medical School, Norwich, UK
- Clinical Biochemistry, Department of Laboratory Medicine and Department of Diabetes and Endocrinology, Norfolk and Norwich University Hospital NHS Foundation Trust, Norwich, UK
| | - Inez Schoenmakers
- University of East Anglia, Norwich Medical School, Norwich, UK
- MRC Human Nutrition Research, Cambridge, UK
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12
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Arabi SM, Shahraki-Jazinaki M, Chambari M, Bahrami LS, Sabeti S, Gubari MIM, Roufogalis BD, Sahebkar A. The effect of oral supplementation of Paricalcitol on C-reactive protein levels in chronic kidney disease patients: GRADE-assessed systematic review and dose-response meta-analysis of data from randomized controlled trials. BMC Pharmacol Toxicol 2024; 25:19. [PMID: 38395972 PMCID: PMC10885610 DOI: 10.1186/s40360-024-00740-y] [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: 11/04/2023] [Accepted: 02/06/2024] [Indexed: 02/25/2024] Open
Abstract
BACKGROUND Previous studies investigating the effect of oral supplementation of paricalcitol on reactive protein levels in chronic kidney disease (CKD) patients reported inconsistent findings. In this systematic review and meta-analysis, we have analyzed and interpreted the results obtained from previous randomized clinical trials on the effect of paricalcitol on C-reactive protein in CKD patients in the literature. METHODS MEDLINE, SciVerse Scopus, and Clarivate Analytics Web of Science databases were searched until January 2023 and related articles were obtained through a careful screening process allowing extraction of required data from selected articles. The effect size was calculated using a random effect model and weighted mean differences (WMD) and 95% confidence intervals (CI). Heterogeneity among studies was evaluated using Cochran's Q test and I2. RESULTS Amongst the 182 articles obtained from the initial search, 4 studies (6 arms) were finally included in the meta-analysis. Pooled analysis shows that C-reactive protein levels significantly decrease after oral supplementation with paricalcitol (WMD: -2.55 mg/L, 95% CI (-4.99 to -0.11; P = 0.04). The studies used in this meta-analysis showed significant heterogeneity (I2 = 66.3% and P = 0.01). CONCLUSION Oral paricalcitol supplementation in CKD patients can significantly reduce C-reactive protein levels, which may prevent CKD progression.
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Affiliation(s)
- Seyyed Mostafa Arabi
- Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran
- Healthy Ageing Research Centre, Neyshabur University of Medical Sciences, Neyshabur, Iran
| | | | - Mahla Chambari
- Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran
| | - Leila Sadat Bahrami
- Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran
- Department of Nutrition, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sara Sabeti
- Department of food science and nutrition, School of Medicine, Gonabad University of Medical Sciences, Gonabad, Iran
| | | | - Basil D Roufogalis
- Discipline of Pharmacology, School of Medical Sciences, University of Sydney, Sydney, NSW, Australia
- NICM Health Research Institute, Western Sydney University, Penrith, NSW, Australia
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
- Applied Biomedical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
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13
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Stack BC. Secondary Hyperparathyroidism. Otolaryngol Clin North Am 2024; 57:99-110. [PMID: 37634982 DOI: 10.1016/j.otc.2023.07.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/29/2023]
Abstract
Secondary hyperparathyroidism (SHPT) does not initiate as a primary dysfunction of parathyroid glands resulting from an intrinsic defect or disease but is the physiologic response of parathyroids to metabolic changes elsewhere in the body occurring over time. SHPT is a manifestation of a chronic condition that classically occurs from chronic kidney disease. In fact, given the relatively recent transition of populations from outside (agrarian) to indoor (industrial, information technology, and so forth) employment and a consequent reduction in sun exposure, combined with diets of highly processed food, vitamin D and calcium deficiencies are now the leading causes of SHPT.
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Affiliation(s)
- Brendan C Stack
- Department of Otolaryngology-HNS Southern Illinois University/SIU Medicine, 720 North Bond Street, PO Box 19662, Springfield, IL 62794-9662, USA.
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14
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Turck D, McArdle HJ, Naska A, Neuhäuser‐Berthold M, Passeri G, Craciun I, Roldán‐Torres R, Valtueña Martínez S. Scientific and technical assistance to the evaluation of the safety of calcidiol monohydrate as a novel food. EFSA J 2024; 22:e8520. [PMID: 38273990 PMCID: PMC10809025 DOI: 10.2903/j.efsa.2024.8520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2024] Open
Abstract
EFSA was asked by the European Commission to provide scientific assistance with respect to the EFSA adopted scientific opinion on 'Safety of calcidiol monohydrate produced by chemical synthesis as a novel food pursuant to Regulation (EU) 2015/2283', including its bioavailability as a metabolite of vitamin D3 when added for nutritional purposes to food supplements. On 5 July 2023, EFSA adopted the 'Scientific opinion on the tolerable upper intake level for vitamin D, including the derivation of a conversion factor for calcidiol monohydrate'. This opinion concerns an updated exposure assessment for vitamin D and proposes a conversion factor for calcidiol monohydrate into vitamin D3 of 2.5 for labelling purposes. In addition, in reference to the EFSA opinion on the safety of calcidiol monohydrate, the Commission had received a letter from the pharmaceutical company EirGen Pharma Ltd requesting a revision of this opinion based on new data concerning calcidiol. Based on the information and data considered in this scientific technical report, EFSA concludes that the novel food calcidiol monohydrate proposed for use in food supplements is a bioavailable source of the biologically active metabolite of vitamin D, i.e. 1,25-dihydroxyvitamin D, that a conversion factor of 2.5 reflects the relative bioavailability of calcidiol vs vitamin D3 under the proposed conditions of use and use levels, and that it is safe under the proposed conditions of use and use levels, i.e. up to 10 μg/day for children ≥ 11 years old and adults, including pregnant and lactating women, and up to 5 μg/day for children 3-10 years of age.
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15
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Adams JS, Shieh A, Bishop CW. Calcifediol as a therapeutic. FELDMAN AND PIKE'S VITAMIN D 2024:457-474. [DOI: 10.1016/b978-0-323-91338-6.00023-9] [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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16
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Yeung WCG, Palmer SC, Strippoli GFM, Talbot B, Shah N, Hawley CM, Toussaint ND, Badve SV. Vitamin D Therapy in Adults With CKD: A Systematic Review and Meta-analysis. Am J Kidney Dis 2023; 82:543-558. [PMID: 37356648 DOI: 10.1053/j.ajkd.2023.04.003] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Accepted: 04/24/2023] [Indexed: 06/27/2023]
Abstract
RATIONALE & OBJECTIVE Vitamin D is widely used to manage chronic kidney disease-mineral and bone disorder (CKD-MBD). We evaluated the effects of vitamin D therapy on mortality, cardiovascular, bone, and kidney outcomes in adults with CKD. STUDY DESIGN Systematic review of randomized controlled trials (RCT) with highly sensitive searching of MEDLINE, Embase, and CENTRAL, through February 25, 2023. SETTING & STUDY POPULATIONS Adults with stage 3, 4, or 5 CKD, including kidney failure treated with dialysis. Recipients of a kidney transplant were excluded. SELECTION CRITERIA FOR STUDIES RCTs with≥3 months of follow-up evaluating a vitamin D compound. DATA EXTRACTION Data were extracted independently by three investigators. ANALYTICAL APPROACH Treatment estimates were summarized using random effects meta-analysis. Primary review endpoints were all-cause death, cardiovascular death, and fracture. Secondary outcomes were major adverse cardiovascular events, hospitalization, bone mineral density, parathyroidectomy, progression to kidney failure, proteinuria, estimated glomerular filtration rate, hypercalcemia, hyperphosphatemia, biochemical markers of CKD-MBD, and various intermediate outcome measures of cardiovascular disease. Risk of bias was assessed using the Cochrane Risk of Bias (RoB) 2 tool. Evidence certainty was adjudicated using GRADE. RESULTS Overall, 128 studies involving 11,270 participants were included. Compared with placebo, vitamin D therapy probably had no effect on all-cause death (relative risk [RR], 1.04; 95% CI, 0.84-1.24); and uncertain effects on fracture (RR, 0.68; 95% CI, 0.37-1.23) and cardiovascular death (RR, 0.73; 95% CI, 0.31-1.71). Compared with placebo, vitamin D therapy lowered serum parathyroid hormone and alkaline phosphatase, but increased serum calcium. LIMITATIONS Data were limited by trials with short-term follow-up periods, small sample size, and the suboptimal quality. CONCLUSIONS Vitamin D therapy did not reduce the risk of all-cause death in people with CKD. Effects on fracture and cardiovascular and kidney outcomes were uncertain. TRIAL REGISTRATION Registered at PROSPERO with study number CRD42017057691. PLAIN-LANGUAGE SUMMARY Chronic kidney disease (CKD) is associated with increased risk of death, cardiovascular disease, and fractures. This excess risk is thought to be related to changes in bone and mineral metabolism, leading to the development of CKD-mineral and bone disorder (CKD-MBD) which is characterized by vascular calcification and reduced bone quality. Vitamin D is commonly used in the treatment of this condition. We reviewed randomized controlled trials examining the effect of vitamin D therapy in CKD. We found that vitamin D therapy affects serum biomarkers, including an increase in serum calcium. However, it probably has no effect on risk of all-cause death in CKD, and the effects on other clinical bone, cardiovascular, and kidney outcomes are uncertain.
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Affiliation(s)
- Wing-Chi G Yeung
- Department of Nephrology, Wollongong Hospital, Sydney, Australia; George Institute for Global Health, Sydney, Australia; Faculty of Medicine, University of New South Wales, Sydney, Australia.
| | - Suetonia C Palmer
- Department of Medicine, University of Otago, Christchurch, New Zealand
| | - Giovanni F M Strippoli
- Sydney School of Public Health, University of Sydney, Sydney, Australia; Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - Benjamin Talbot
- George Institute for Global Health, Sydney, Australia; Faculty of Medicine, University of New South Wales, Sydney, Australia
| | - Nasir Shah
- Faculty of Medicine, University of New South Wales, Sydney, Australia
| | - Carmel M Hawley
- Translational Research Institute, Brisbane, Australia; Department of Nephrology, Princess Alexandra Hospital, Brisbane, Australia; Australasian Kidney Trials Network, University of Queensland, Brisbane, Australia
| | - Nigel D Toussaint
- Department of Nephrology, Royal Melbourne Hospital, Parkville, Australia; Department of Medicine, University of Melbourne, Parkville, Australia
| | - Sunil V Badve
- Department of Nephrology, St George Hospital, Sydney, Australia; George Institute for Global Health, Sydney, Australia; Faculty of Medicine, University of New South Wales, Sydney, Australia
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17
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Fusaro M, Pereira L, Bover J. Current and Emerging Markers and Tools Used in the Diagnosis and Management of Chronic Kidney Disease-Mineral and Bone Disorder in Non-Dialysis Adult Patients. J Clin Med 2023; 12:6306. [PMID: 37834950 PMCID: PMC10573159 DOI: 10.3390/jcm12196306] [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: 08/02/2023] [Revised: 09/19/2023] [Accepted: 09/27/2023] [Indexed: 10/15/2023] Open
Abstract
Chronic kidney disease (CKD) is a significant public health concern associated with significant morbidity and has become one of the foremost global causes of death in recent years. A frequent comorbidity of CKD is secondary hyperparathyroidism (SHPT), exemplified by high serum parathyroid hormone (PTH) levels. The mineral metabolism disturbances resulting from CKD and progression to SHPT are currently considered part of the definition of chronic kidney disease-mineral and bone disorder (CKD-MBD). However, CKD-MBD does not only include abnormalities in laboratory-measured parameters; it is a complex condition characterized by dysregulation of bone turnover, mineralization, growth and strength, accompanied by vascular or another soft-tissue calcification. Together, this increases the risk of bone fractures, cardiovascular disease, and overall mortality in CKD-MBD patients. Monitoring serum markers is essential in diagnosing SHPT and CKD-MBD, and there are several recognized indicators for prognosis, optimal clinical management and treatment response in late-stage kidney disease patients receiving dialysis. However, far fewer markers have been established for patients with non-dialysis CKD. This review provides an overview of current and emerging markers and tools used in the diagnosis and management of CKD-MBD in non-dialysis adult patients.
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Affiliation(s)
- Maria Fusaro
- National Research Council (CNR)—Institute of Clinical Physiology (IFC), Via G. Moruzzi 1, 56124 Pisa, Italy
- Department of Medicine, University of Padova, Via Giustiniani, 2, 35128 Padova, Italy
| | - Luciano Pereira
- Institute of Investigation and Innovation in Health, University of Porto, 4200-135 Porto, Portugal
- INEB—National Institute of Biomedical Engineering, University of Porto, 4150-180 Porto, Portugal
- DaVita Kidney Care, 4200-448 Porto, Portugal
- Faculty of Medicine, University of Porto, 4200-250 Porto, Portugal
| | - Jordi Bover
- Nephrology Department, University Hospital Germans Trias i Pujol (HGiTP), 08916 Barcelona, Spain
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18
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Lu Y, Ning Y, Li Y, Zhu B, Zhang J, Yang Y, Chen W, Yan Z, Chen A, Shen B, Fang Y, Wang D, Song N, Ding X. Risk factor mining and prediction of urine protein progression in chronic kidney disease: a machine learning- based study. BMC Med Inform Decis Mak 2023; 23:173. [PMID: 37653403 PMCID: PMC10472702 DOI: 10.1186/s12911-023-02269-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 08/17/2023] [Indexed: 09/02/2023] Open
Abstract
BACKGROUND Chronic kidney disease (CKD) is a global public health concern. Therefore, to provide timely intervention for non-hospitalized high-risk patients and rationally allocate limited clinical resources is important to mine the key factors when designing a CKD prediction model. METHODS This study included data from 1,358 patients with CKD pathologically confirmed during the period from December 2017 to September 2020 at Zhongshan Hospital. A CKD prediction interpretation framework based on machine learning was proposed. From among 100 variables, 17 were selected for the model construction through a recursive feature elimination with logistic regression feature screening. Several machine learning classifiers, including extreme gradient boosting, gaussian-based naive bayes, a neural network, ridge regression, and linear model logistic regression (LR), were trained, and an ensemble model was developed to predict 24-hour urine protein. The detailed relationship between the risk of CKD progression and these predictors was determined using a global interpretation. A patient-specific analysis was conducted using a local interpretation. RESULTS The results showed that LR achieved the best performance, with an area under the curve (AUC) of 0.850 in a single machine learning model. The ensemble model constructed using the voting integration method further improved the AUC to 0.856. The major predictors of moderate-to-severe severity included lower levels of 25-OH-vitamin, albumin, transferrin in males, and higher levels of cystatin C. CONCLUSIONS Compared with the clinical single kidney function evaluation indicators (eGFR, Scr), the machine learning model proposed in this study improved the prediction accuracy of CKD progression by 17.6% and 24.6%, respectively, and the AUC was improved by 0.250 and 0.236, respectively. Our framework can achieve a good predictive interpretation and provide effective clinical decision support.
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Affiliation(s)
- Yufei Lu
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai Clinical Research Center for Kidney Disease, Shanghai Medical Center of Kidney, Shanghai Institute of Kidney and Dialysis, Shanghai Key Laboratory of Kidney and Blood Purification, Hemodialysis Quality Control Center of Shanghai, Shanghai, China
| | - Yichun Ning
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai Clinical Research Center for Kidney Disease, Shanghai Medical Center of Kidney, Shanghai Institute of Kidney and Dialysis, Shanghai Key Laboratory of Kidney and Blood Purification, Hemodialysis Quality Control Center of Shanghai, Shanghai, China
| | - Yang Li
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai Clinical Research Center for Kidney Disease, Shanghai Medical Center of Kidney, Shanghai Institute of Kidney and Dialysis, Shanghai Key Laboratory of Kidney and Blood Purification, Hemodialysis Quality Control Center of Shanghai, Shanghai, China
| | - Bowen Zhu
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai Clinical Research Center for Kidney Disease, Shanghai Medical Center of Kidney, Shanghai Institute of Kidney and Dialysis, Shanghai Key Laboratory of Kidney and Blood Purification, Hemodialysis Quality Control Center of Shanghai, Shanghai, China
| | - Jian Zhang
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai Clinical Research Center for Kidney Disease, Shanghai Medical Center of Kidney, Shanghai Institute of Kidney and Dialysis, Shanghai Key Laboratory of Kidney and Blood Purification, Hemodialysis Quality Control Center of Shanghai, Shanghai, China
| | - Yan Yang
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai Clinical Research Center for Kidney Disease, Shanghai Medical Center of Kidney, Shanghai Institute of Kidney and Dialysis, Shanghai Key Laboratory of Kidney and Blood Purification, Hemodialysis Quality Control Center of Shanghai, Shanghai, China
| | - Weize Chen
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai Clinical Research Center for Kidney Disease, Shanghai Medical Center of Kidney, Shanghai Institute of Kidney and Dialysis, Shanghai Key Laboratory of Kidney and Blood Purification, Hemodialysis Quality Control Center of Shanghai, Shanghai, China
| | - Zhixin Yan
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai Clinical Research Center for Kidney Disease, Shanghai Medical Center of Kidney, Shanghai Institute of Kidney and Dialysis, Shanghai Key Laboratory of Kidney and Blood Purification, Hemodialysis Quality Control Center of Shanghai, Shanghai, China
| | - Annan Chen
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai Clinical Research Center for Kidney Disease, Shanghai Medical Center of Kidney, Shanghai Institute of Kidney and Dialysis, Shanghai Key Laboratory of Kidney and Blood Purification, Hemodialysis Quality Control Center of Shanghai, Shanghai, China
| | - Bo Shen
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai Clinical Research Center for Kidney Disease, Shanghai Medical Center of Kidney, Shanghai Institute of Kidney and Dialysis, Shanghai Key Laboratory of Kidney and Blood Purification, Hemodialysis Quality Control Center of Shanghai, Shanghai, China
| | - Yi Fang
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai Clinical Research Center for Kidney Disease, Shanghai Medical Center of Kidney, Shanghai Institute of Kidney and Dialysis, Shanghai Key Laboratory of Kidney and Blood Purification, Hemodialysis Quality Control Center of Shanghai, Shanghai, China
| | - Dong Wang
- School of Computer Science & Information Engineering, Shanghai Institute of Technology, Shanghai, China.
| | - Nana Song
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai Clinical Research Center for Kidney Disease, Shanghai Medical Center of Kidney, Shanghai Institute of Kidney and Dialysis, Shanghai Key Laboratory of Kidney and Blood Purification, Hemodialysis Quality Control Center of Shanghai, Shanghai, China.
| | - Xiaoqiang Ding
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai Clinical Research Center for Kidney Disease, Shanghai Medical Center of Kidney, Shanghai Institute of Kidney and Dialysis, Shanghai Key Laboratory of Kidney and Blood Purification, Hemodialysis Quality Control Center of Shanghai, Shanghai, China.
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Grubczak K, Starosz A, Makowska B, Parfienowicz Z, Krętowska M, Naumnik B, Moniuszko M. The influence of calcitriol and methylprednisolone on podocytes function in minimal change disease in vitro model. Sci Rep 2023; 13:12731. [PMID: 37543700 PMCID: PMC10404287 DOI: 10.1038/s41598-023-39893-x] [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: 04/13/2023] [Accepted: 08/01/2023] [Indexed: 08/07/2023] Open
Abstract
Minimal change disease (MCD), considered one of the major causes of nephrotic syndrome, is a complex pathological condition with disturbances in podocytes' foot processes. Numerous studies suggested the essential role of vitamin D3 in maintaining proper glomerulus function. However, the data on direct potential of that compound in reference to podocytes are scarce. Thus, here we assessed the influence of calcitriol (active vitamin D3) on podocyte function, apart from commonly used steroids (methylprednisolone). CIHP-1 podocyte cell line was used to implement the LPS-PAN-induced MCD in vitro model. Viability, podocyte-related slit diaphragm proteins, morphology, function as a barrier was evaluated using flow cytometry, RT-PCR, confocal microscopy, and TEER analysis. Calcitriol or methylprednisolone did not affect cell viability. Podocyte-related proteins demonstrated different responses to in vitro treatment compared to previously reported changes in total glomeruli. Podocyte morphology was partially restored in the presence of the tested compounds. In addition, TEER analysis revealed improvement of LPS-PAN-induced cells' function as a barrier when vitamin D3 or steroid was used. In conclusion, a significant potential for modulation of MCD in vitro model podocytes with calcitriol or selected steroids was reported. Further studies on vitamin D3 in context of podocyte-related phenomenon accompanying MCD are of great importance.
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Affiliation(s)
- Kamil Grubczak
- Department of Regenerative Medicine and Immune Regulation, Medical University of Białystok, Jerzego Waszyngtona 13, 15-269, Białystok, Poland.
| | - Aleksandra Starosz
- Department of Regenerative Medicine and Immune Regulation, Medical University of Białystok, Jerzego Waszyngtona 13, 15-269, Białystok, Poland
| | - Barbara Makowska
- Department of Regenerative Medicine and Immune Regulation, Medical University of Białystok, Jerzego Waszyngtona 13, 15-269, Białystok, Poland
| | - Zuzanna Parfienowicz
- Department of Regenerative Medicine and Immune Regulation, Medical University of Białystok, Jerzego Waszyngtona 13, 15-269, Białystok, Poland
| | - Magdalena Krętowska
- Department of Regenerative Medicine and Immune Regulation, Medical University of Białystok, Jerzego Waszyngtona 13, 15-269, Białystok, Poland
| | - Beata Naumnik
- Ist Department of Nephrology and Transplantation with Dialysis Unit, Medical University of Bialystok, Żurawia 14, 15-540, Białystok, Poland.
| | - Marcin Moniuszko
- Department of Regenerative Medicine and Immune Regulation, Medical University of Białystok, Jerzego Waszyngtona 13, 15-269, Białystok, Poland
- Department of Allergology and Internal Medicine, Medical University of Białystok, Marii Skłodowskiej-Curie 24A, 15-276, Białystok, Poland
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20
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Yoshida S, Shiraishi R, Nakayama Y, Taira Y. Can Nutrition Contribute to a Reduction in Sarcopenia, Frailty, and Comorbidities in a Super-Aged Society? Nutrients 2023; 15:2991. [PMID: 37447315 DOI: 10.3390/nu15132991] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Revised: 06/28/2023] [Accepted: 06/28/2023] [Indexed: 07/15/2023] Open
Abstract
Many countries are facing the advent of super-aging societies, where sarcopenia and frailty will become pertinent problems. The prevalence of comorbidities is a major problem in countries with aged populations as elderly people suffer from various diseases, such as diabetes, heart failure, chronic kidney disease and dementia. All of these diseases are associated with sarcopenia and frailty, and they frequently cause falls, fractures, and a decline in activities of daily living. Fractures in the elderly people are associated with bone fragility, which is influenced by diabetes and chronic kidney disease. Nutritional support for chronic disease patients and sarcopenic individuals with adequate energy and protein intake, vitamin D supplementation, blood glucose level management for individuals with diabetes, obesity prevention, nutritional education for healthy individuals, and the enlightenment of society could be crucial to solve the health-related problems in super-aging societies.
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Affiliation(s)
- Sadao Yoshida
- Department of Rehabilitation, Chuzan Hospital, 6-2-1 Matsumoto, Okinawa 904-2151, Okinawa, Japan
- Department of Health and Nutrition, Okinawa University, 555 Kokuba, Naha 902-8521, Okinawa, Japan
- Faculty of Health Sciences, Kinjo University, 1200 Kasama-machi, Hakusan 924-8511, Ishikawa, Japan
| | - Ryo Shiraishi
- Department of Rehabilitation, Chuzan Hospital, 6-2-1 Matsumoto, Okinawa 904-2151, Okinawa, Japan
| | - Yuki Nakayama
- Department of Rehabilitation, Chuzan Hospital, 6-2-1 Matsumoto, Okinawa 904-2151, Okinawa, Japan
| | - Yasuko Taira
- Faculty of Nutrition, Chuzan Hospital, 6-2-1 Matsumoto, Okinawa 904-2151, Okinawa, Japan
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21
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Ahmad S, Ullah H, Khan MI, Gul M, Ahmed MS, Khalil M, Ahmad M, Khan AB. Effect of Vitamin D Supplementation on the Hemoglobin Level in Chronic Kidney Disease Patients on Hemodialysis: A Systematic Review and Meta-Analysis. Cureus 2023; 15:e40843. [PMID: 37489201 PMCID: PMC10363281 DOI: 10.7759/cureus.40843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/22/2023] [Indexed: 07/26/2023] Open
Abstract
The objective of this study was to evaluate the impact of vitamin D supplementation on hemoglobin levels (Hb) in patients with chronic kidney disease (CKD) undergoing hemodialysis. A systematic search was conducted in electronic databases (PubMed/Medline, Cochrane Library, and Google Scholar) from inception to April 21, 2023. Inclusion criteria were applied to select relevant studies. Statistical analyses were performed using Review Manager 5.4.1. A random-effects model was used to address heterogeneity, and the mean difference (MD) with the corresponding 95% confidence interval (CI) was reported. Ten studies were included in the analysis, comprising seven clinical trials, two randomized clinical trials, and one retrospective observational study. Subgroup analysis was conducted based on the duration of follow-up: 12 weeks, three months, six months, 12 months, 15 months, and 18 months. A significant increase in hemoglobin levels was observed after 12 months (MD = -0.98 [95% CI -1.88, -0.08]; p = 0.03; I2 = 91%) and 18 months (MD = -1.80 [95% CI -2.56, -1.04]; p < 0.00001; I2 = Not applicable). However, there was no statistically significant relationship between vitamin D supplementation and hemoglobin levels at 12 weeks, three months, six months, and 15 months. The pooled analysis demonstrated a significant increase in hemoglobin levels with vitamin D supplementation (MD = -0.61 [95% CI -0.96, -0.26]; p = 0.03; I2 = 60.7%). This analysis highlights the significant role of vitamin D supplementation in improving anemia in patients with CKD undergoing hemodialysis. Vitamin D supplementation was found to significantly increase hemoglobin levels, particularly after 12 months and 18 months of supplementation.
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Affiliation(s)
- Saad Ahmad
- Orthopedic Surgery, Taj Medical Center, Nowshera, PAK
| | | | - Moiz I Khan
- Accident and Emergency, Medical Teaching Institution (MTI) Divisional Headquarter (DHQ) Teaching Hospital, Dera Ismail Khan, PAK
| | - Maryam Gul
- Internal Medicine, Taj Medical Center, Nowshera, PAK
| | | | - Maha Khalil
- Gastroenterology and Hepatology, Shalamar Medical and Dental College, Lahore, PAK
| | - Mateen Ahmad
- Surgery, Khyber Teaching Hospital, Peshawar, PAK
| | - Abu Baker Khan
- Internal Medicine, Ayub Teaching Hospital, Abbottabad, PAK
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22
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Grant WB, Al Anouti F, Boucher BJ, Fakhoury HMA, Moukayed M, Pilz S, Al-Daghri NM. Evidence That Increasing Serum 25(OH)D Concentrations to 30 ng/mL in the Kingdom of Saudi Arabia and the United Arab Emirates Could Greatly Improve Health Outcomes. Biomedicines 2023; 11:994. [PMID: 37189612 PMCID: PMC10136066 DOI: 10.3390/biomedicines11040994] [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: 02/27/2023] [Revised: 03/17/2023] [Accepted: 03/21/2023] [Indexed: 03/30/2023] Open
Abstract
Accumulating evidence supports the potential protective effects of vitamin D against chronic diseases such as Alzheimer's disease, autoimmune diseases, cancers, cardiovascular disease (ischaemic heart disease and stroke), type 2 diabetes, hypertension, chronic kidney disease, stroke, and infectious diseases such as acute respiratory tract diseases, COVID-19, influenza, and pneumonia, as well as adverse pregnancy outcomes. The respective evidence is based on ecological and observational studies, randomized controlled trials, mechanistic studies, and Mendelian randomization studies. However, randomized controlled trials on vitamin D supplementation have largely failed to show benefits, probably due to poor design and analysis. In this work, we aim to use the best available evidence on the potential beneficial effects of vitamin D to estimate the expected reduction in incidence and mortality rates of vitamin D-related diseases in the Kingdom of Saudi Arabia and the United Arab Emirates if minimum serum 25(OH)D concentrations were to be raised to 30 ng/mL. Estimated reductions by 25% for myocardial infarction incidence, 35% for stroke incidence, 20 to 35% for cardiovascular disease mortality, and 35% for cancer mortality rates depicted a promising potential for raising serum 25(OH)D. Methods to increase serum 25(OH)D concentrations at the population level could include food fortification with vitamin D3, vitamin D supplementation, improved dietary vitamin D intake, and sensible sun exposure.
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Affiliation(s)
- William B. Grant
- Sunlight, Nutrition, and Health Research Center, P.O. Box 641603, San Francisco, CA 94164-1603, USA
| | - Fatme Al Anouti
- Department of Health Sciences, College of Natural and Health Sciences, Zayed University, Abu Dhabi P.O. Box 144534, United Arab Emirates
| | - Barbara J. Boucher
- The Blizard Institute, Barts & The London School of Medicine & Dentistry, Queen Mary University of London, London E12AT, UK
| | - Hana M. A. Fakhoury
- Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia
| | - Meis Moukayed
- School of Arts and Sciences, American University in Dubai, Dubai P.O. Box 28282, United Arab Emirates
| | - Stefan Pilz
- Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria
| | - Nasser M. Al-Daghri
- Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
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23
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Martinelli RP, Rayego-Mateos S, Alique M, Márquez-Expósito L, Tejedor-Santamaria L, Ortiz A, González-Parra E, Ruiz-Ortega M. Vitamin D, Cellular Senescence and Chronic Kidney Diseases: What Is Missing in the Equation? Nutrients 2023; 15:1349. [PMID: 36986078 PMCID: PMC10056834 DOI: 10.3390/nu15061349] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Revised: 03/07/2023] [Accepted: 03/09/2023] [Indexed: 03/12/2023] Open
Abstract
As life expectancy increases in many countries, the prevalence of age-related diseases also rises. Among these conditions, chronic kidney disease is predicted to become the second cause of death in some countries before the end of the century. An important problem with kidney diseases is the lack of biomarkers to detect early damage or to predict the progression to renal failure. In addition, current treatments only retard kidney disease progression, and better tools are needed. Preclinical research has shown the involvement of the activation of cellular senescence-related mechanisms in natural aging and kidney injury. Intensive research is searching for novel treatments for kidney diseases as well as for anti-aging therapies. In this sense, many experimental shreds of evidence support that treatment with vitamin D or its analogs can exert pleiotropic protective effects in kidney injury. Moreover, vitamin D deficiency has been described in patients with kidney diseases. Here, we review recent evidence about the relationship between vitamin D and kidney diseases, explaining the underlying mechanisms of the effect of vitamin D actions, with particular attention to the modulation of cellular senescence mechanisms.
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Affiliation(s)
- Romina P. Martinelli
- Cellular Biology in Renal Diseases Laboratory, IIS-Fundación Jiménez Díaz-Universidad Autónoma, 28040 Madrid, Spain
| | - Sandra Rayego-Mateos
- Cellular Biology in Renal Diseases Laboratory, IIS-Fundación Jiménez Díaz-Universidad Autónoma, 28040 Madrid, Spain
- Ricors2040, 28029 Madrid, Spain
| | - Matilde Alique
- Ricors2040, 28029 Madrid, Spain
- Departamento de Biología de Sistemas, Universidad de Alcalá, Alcalá de Henares, 28871 Madrid, Spain
- Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain
| | - Laura Márquez-Expósito
- Cellular Biology in Renal Diseases Laboratory, IIS-Fundación Jiménez Díaz-Universidad Autónoma, 28040 Madrid, Spain
- Ricors2040, 28029 Madrid, Spain
| | - Lucia Tejedor-Santamaria
- Cellular Biology in Renal Diseases Laboratory, IIS-Fundación Jiménez Díaz-Universidad Autónoma, 28040 Madrid, Spain
- Ricors2040, 28029 Madrid, Spain
| | - Alberto Ortiz
- Ricors2040, 28029 Madrid, Spain
- Department of Nephrology and Hypertension, IIS-Fundación Jiménez Díaz-Universidad Autónoma Madrid, 28040 Madrid, Spain
| | - Emilio González-Parra
- Ricors2040, 28029 Madrid, Spain
- Department of Nephrology and Hypertension, IIS-Fundación Jiménez Díaz-Universidad Autónoma Madrid, 28040 Madrid, Spain
| | - Marta Ruiz-Ortega
- Cellular Biology in Renal Diseases Laboratory, IIS-Fundación Jiménez Díaz-Universidad Autónoma, 28040 Madrid, Spain
- Ricors2040, 28029 Madrid, Spain
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24
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Alonso N, Zelzer S, Eibinger G, Herrmann M. Vitamin D Metabolites: Analytical Challenges and Clinical Relevance. Calcif Tissue Int 2023; 112:158-177. [PMID: 35238975 PMCID: PMC8892115 DOI: 10.1007/s00223-022-00961-5] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Accepted: 02/16/2022] [Indexed: 01/25/2023]
Abstract
Recent research activities have provided new insights in vitamin D metabolism in various conditions. Furthermore, substantial progress has been made in the analysis of vitamin D metabolites and related biomarkers, such as vitamin D binding protein. Liquid chromatography tandem mass spectrometric (LC-MS/MS) methods are capable of accurately measuring multiple vitamin D metabolites in parallel. Nevertheless, only 25(OH)D and the biologically active form 1,25(OH)2D are routinely measured in clinical practice. While 25(OH)D remains the analyte of choice for the diagnosis of vitamin D deficiency, 1,25(OH)2D is only recommended in a few conditions with a dysregulated D metabolism. 24,25(OH)2D, free and bioavailable 25(OH)D, and the vitamin D metabolite ratio (VMR) have shown promising results, but technical pitfalls in their quantification, limited clinical data and the lack of reference values, impede their use in clinical practice. LC-MS/MS is the preferred method for the measurement of all vitamin D related analytes as it offers high sensitivity and specificity. In particular, 25(OH)D and 24,25(OH)2D can accurately be measured with this technology. When interpreted together, they seem to provide a functional measure of vitamin D metabolism beyond the analysis of 25(OH)D alone. The determination of VDBP, free and bioavailable 25(OH)D is compromised by unresolved analytical issues, lacking reference intervals and insufficient clinical data. Therefore, future research activities should focus on analytical standardization and exploration of their clinical value. This review provides an overview on established and new vitamin D related biomarkers including their pathophysiological role, preanalytical and analytical aspects, expected values, indications and influencing conditions.
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Affiliation(s)
- N Alonso
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
| | - S Zelzer
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
| | - G Eibinger
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
| | - M Herrmann
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
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25
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Limonte CP, Zelnick LR, Hoofnagle AN, Thadhani R, Melamed ML, Mora S, Cook NR, Luttmann-Gibson H, Sesso HD, Lee IM, Buring JE, Manson JE, de Boer IH. Effects of Vitamin D 3 Supplementation on Cardiovascular and Cancer Outcomes by eGFR in VITAL. KIDNEY360 2022; 3:2095-2105. [PMID: 36591342 PMCID: PMC9802543 DOI: 10.34067/kid.0006472022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Accepted: 10/19/2022] [Indexed: 04/26/2023]
Abstract
Background Reduced 25-hydroxyvitamin D (25[OH]D) metabolism and secondary hyperparathyroidism are common with lower estimated glomerular filtration rate (eGFR) and may contribute to cardiovascular disease and cancer risk. Methods We assessed for heterogeneity by baseline eGFR of the effects of vitamin D3 on cardiovascular and cancer outcomes in the Vitamin D and Omega-3 Trial (VITAL). Participants were randomized to 2000 IU vitamin D3 and/or 1 g Ω-3 fatty acids daily using a placebo-controlled, two-by-two factorial design (5.3 years follow-up). Primary study end points were incident major cardiovascular events and invasive cancer. Changes in serum 25(OH)D and parathyroid hormone (PTH) were examined. Results Baseline eGFR was available for 15,917 participants. Participants' mean age was 68 years, and 51% were women. Vitamin D3 resulted in higher serum 25(OH)D compared with placebo (difference in change 12.5 ng/ml; 95% CI, 12 to 13.1 ng/ml), without heterogeneity by eGFR (P interaction, continuous eGFR=0.2). Difference in change in PTH between vitamin D3 and placebo was larger with lower eGFR (P interaction=0.05): -6.9 (95% CI, -10.5 to -3.4), -5.8 (95% CI, -8.3 to -3.4), -4 (95% CI, -5.9 to -2.2), and -3.8 (95% CI, -5.6 to -2) pg/ml for eGFR <60, 60-74, 75-89, and ≥90 ml/min per 1.73 m2, respectively. Effects of vitamin D3 supplementation on cardiovascular events (P interaction=0.61) and cancer (P interaction=0.89) did not differ by eGFR: HR=1.14 (95% CI, 0.73 to 1.79), HR=1.06 (95% CI, 0.75 to 1.5), HR=0.92 (95% CI, 0.67 to 1.25), and HR=0.92 (95% CI, 0.66 to 1.27) across eGFR categories for cardiovascular events and HR=1.63 (95% CI, 1.03 to 2.58), HR=0.85 (95% CI, 0.64 to 1.11), HR=0.84 (95% CI, 0.68 to 1.03), and 1.11 (95% CI, 0.92 to 1.35) for cancer, respectively. Conclusions We observed no significant heterogeneity by baseline eGFR in the effects of vitamin D3 supplementation versus placebo on cardiovascular or cancer outcomes, despite effects on 25(OH)D and PTH concentrations.
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Affiliation(s)
- Christine P Limonte
- Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington
- Kidney Research Institute, University of Washington, Seattle, Washington
| | - Leila R Zelnick
- Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington
- Kidney Research Institute, University of Washington, Seattle, Washington
| | - Andrew N Hoofnagle
- Kidney Research Institute, University of Washington, Seattle, Washington
- Department of Laboratory Medicine, University of Washington, Seattle, Washington
| | - Ravi Thadhani
- Office of the Chief Academic Officer, Mass General Brigham, Boston, Massachusetts
| | - Michal L Melamed
- Division of Nephrology, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York
| | - Samia Mora
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts
- Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Nancy R Cook
- Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Heike Luttmann-Gibson
- Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Howard D Sesso
- Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - I-Min Lee
- Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Julie E Buring
- Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - JoAnn E Manson
- Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Ian H de Boer
- Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington
- Kidney Research Institute, University of Washington, Seattle, Washington
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26
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Potrykus M, Czaja-Stolc S, Małgorzewicz S, Proczko-Stepaniak M, Dębska-Ślizień A. Diet Management of Patients with Chronic Kidney Disease in Bariatric Surgery. Nutrients 2022; 15:nu15010165. [PMID: 36615822 PMCID: PMC9824280 DOI: 10.3390/nu15010165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 12/23/2022] [Accepted: 12/26/2022] [Indexed: 12/31/2022] Open
Abstract
Morbid obesity is considered a civilization disease of the 21st century. Not only does obesity increase mortality, but it is also the most important cause of the shortening life expectancy in the modern world. Obesity is associated with many metabolic abnormalities: dyslipidemia, hyperglycemia, cardiovascular diseases, and others. An increasing number of patients diagnosed with chronic kidney disease (CKD) are obese. Numerous additional disorders associated with impaired kidney function make it difficult to conduct slimming therapy and may also be associated with a greater number of complications than in people with normal kidney function. Currently available treatments for obesity include lifestyle modification, pharmacotherapy, and bariatric surgery (BS). There are no precise recommendations on how to reduce excess body weight in patients with CKD treated conservatively, undergoing chronic dialysis, or after kidney transplantation. The aim of this study was to analyze studies on the bariatric treatment of obesity in this group of people, as well as to compare the recommendations typical for bariatrics and CKD.
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Affiliation(s)
- Marta Potrykus
- Department of General, Endocrine and Transplant Surgery, Medical University of Gdansk, 80-211 Gdańsk, Poland
| | - Sylwia Czaja-Stolc
- Department of Clinical Nutrition, Medical University of Gdansk, 80-211 Gdańsk, Poland
- Correspondence: ; Tel.: +48-(58)-349-27-24
| | - Sylwia Małgorzewicz
- Department of Clinical Nutrition, Medical University of Gdansk, 80-211 Gdańsk, Poland
| | - Monika Proczko-Stepaniak
- Department of General, Endocrine and Transplant Surgery, Medical University of Gdansk, 80-211 Gdańsk, Poland
| | - Alicja Dębska-Ślizień
- Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdansk, 80-952 Gdańsk, Poland
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27
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Latic N, Erben RG. Interaction of Vitamin D with Peptide Hormones with Emphasis on Parathyroid Hormone, FGF23, and the Renin-Angiotensin-Aldosterone System. Nutrients 2022; 14:nu14235186. [PMID: 36501215 PMCID: PMC9736617 DOI: 10.3390/nu14235186] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 11/29/2022] [Accepted: 12/01/2022] [Indexed: 12/12/2022] Open
Abstract
The seminal discoveries that parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) are major endocrine regulators of vitamin D metabolism led to a significant improvement in our understanding of the pivotal roles of peptide hormones and small proteohormones in the crosstalk between different organs, regulating vitamin D metabolism. The interaction of vitamin D, FGF23 and PTH in the kidney is essential for maintaining mineral homeostasis. The proteohormone FGF23 is mainly secreted from osteoblasts and osteoclasts in the bone. FGF23 acts on proximal renal tubules to decrease production of the active form of vitamin D (1,25(OH)2D) by downregulating transcription of 1α-hydroxylase (CYP27B1), and by activating transcription of the key enzyme responsible for vitamin D degradation, 24-hydroxylase (CYP24A1). Conversely, the peptide hormone PTH stimulates 1,25(OH)2D renal production by upregulating the expression of 1α-hydroxylase and downregulating that of 24-hydroxylase. The circulating concentration of 1,25(OH)2D is a positive regulator of FGF23 secretion in the bone, and a negative regulator of PTH secretion from the parathyroid gland, forming feedback loops between kidney and bone, and between kidney and parathyroid gland, respectively. In recent years, it has become clear that vitamin D signaling has important functions beyond mineral metabolism. Observation of seasonal variations in blood pressure and the subsequent identification of vitamin D receptor (VDR) and 1α-hydroxylase in non-renal tissues such as cardiomyocytes, endothelial and smooth muscle cells, suggested that vitamin D may play a role in maintaining cardiovascular health. Indeed, observational studies in humans have found an association between vitamin D deficiency and hypertension, left ventricular hypertrophy and heart failure, and experimental studies provided strong evidence for a role of vitamin D signaling in the regulation of cardiovascular function. One of the proposed mechanisms of action of vitamin D is that it functions as a negative regulator of the renin-angiotensin-aldosterone system (RAAS). This finding established a novel link between vitamin D and RAAS that was unexplored until then. During recent years, major progress has been made towards a more complete understanding of the mechanisms by which FGF23, PTH, and RAAS regulate vitamin D metabolism, especially at the genomic level. However, there are still major gaps in our knowledge that need to be filled by future research. The purpose of this review is to highlight our current understanding of the molecular mechanisms underlying the interaction between vitamin D, FGF23, PTH, and RAAS, and to discuss the role of these mechanisms in physiology and pathophysiology.
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28
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Janoušek J, Pilařová V, Macáková K, Nomura A, Veiga-Matos J, Silva DDD, Remião F, Saso L, Malá-Ládová K, Malý J, Nováková L, Mladěnka P. Vitamin D: sources, physiological role, biokinetics, deficiency, therapeutic use, toxicity, and overview of analytical methods for detection of vitamin D and its metabolites. Crit Rev Clin Lab Sci 2022; 59:517-554. [PMID: 35575431 DOI: 10.1080/10408363.2022.2070595] [Citation(s) in RCA: 65] [Impact Index Per Article: 21.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Vitamin D has a well-known role in the calcium homeostasis associated with the maintenance of healthy bones. It increases the efficiency of the intestinal absorption of dietary calcium, reduces calcium losses in urine, and mobilizes calcium stored in the skeleton. However, vitamin D receptors are present ubiquitously in the human body and indeed, vitamin D has a plethora of non-calcemic functions. In contrast to most vitamins, sufficient vitamin D can be synthesized in human skin. However, its production can be markedly decreased due to factors such as clothing, sunscreens, intentional avoidance of the direct sunlight, or the high latitude of the residence. Indeed, more than one billion people worldwide are vitamin D deficient, and the deficiency is frequently undiagnosed. The chronic deficiency is not only associated with rickets/osteomalacia/osteoporosis but it is also linked to a higher risk of hypertension, type 1 diabetes, multiple sclerosis, or cancer. Supplementation of vitamin D may be hence beneficial, but the intake of vitamin D should be under the supervision of health professionals because overdosing leads to intoxication with severe health consequences. For monitoring vitamin D, several analytical methods are employed, and their advantages and disadvantages are discussed in detail in this review.
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Affiliation(s)
- Jiří Janoušek
- Department of Pharmacognosy, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
| | - Veronika Pilařová
- Department of Analytical Chemistry, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
| | - Kateřina Macáková
- Department of Pharmacognosy, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
| | - Anderson Nomura
- UCIBIO - Applied Molecular Biosciences Unit, REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.,Associate Laboratory i4HB - Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, Porto, Portugal
| | - Jéssica Veiga-Matos
- UCIBIO - Applied Molecular Biosciences Unit, REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.,Associate Laboratory i4HB - Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, Porto, Portugal
| | - Diana Dias da Silva
- UCIBIO - Applied Molecular Biosciences Unit, REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.,Associate Laboratory i4HB - Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, Porto, Portugal.,TOXRUN - Toxicology Research Unit, University Institute of Health Sciences, CESPU CRL, Gandra, Portugal
| | - Fernando Remião
- UCIBIO - Applied Molecular Biosciences Unit, REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.,Associate Laboratory i4HB - Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, Porto, Portugal
| | - Luciano Saso
- Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University of Rome, Rome, Italy
| | - Kateřina Malá-Ládová
- Department of Social and Clinical Pharmacy, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
| | - Josef Malý
- Department of Social and Clinical Pharmacy, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
| | - Lucie Nováková
- Department of Analytical Chemistry, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
| | - Přemysl Mladěnka
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
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Rios P, Silvariño R, Sola L, Ferreiro A, Lamadrid V, Fajardo L, Gadola L. Mineral and bone disorder and longterm survival in a chronic kidney disease grade 3b-4cohort. Ren Fail 2022; 44:1356-1367. [PMID: 35946486 PMCID: PMC9373789 DOI: 10.1080/0886022x.2022.2107543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Revised: 07/13/2022] [Accepted: 07/24/2022] [Indexed: 11/13/2022] Open
Abstract
Mineral and bone disorder biomarkers 'normal ranges' are controversial. The aim of the study was to evaluate the association between serum calcium (Ca), phosphate (P), intact parathyroid hormone (iPTH), and 25(OH) vitamin D levels and mortality risk, in a chronic kidney disease (CKD) grade (G) 3b-4 cohort. The Uruguayan National Renal Healthcare Program (NRHP-UY) CKD patients' cohort, included between 1 October 2004 and 1 March 2020 and followed-up until 1 March 2021, was analyzed with the Ethics Committee approval. A total of 6473 patients were analyzed: 56% men, median age 73 (65-79) years, 55% on CKD G3b. At the end of the follow-up, 2459 (37.7%) patients had died (6.4/100 patient-year). There were iPTH data on 2013 patients (younger, with lower estimated glomerular filtration rate (eGFR) and lesser comorbidities). By bivariate Cox analysis the lowest death risk was observed with mean Ca between 9.01 and 10.25 mg/dl, P between 2.76 and 4.0 mg/dl, iPTH ≤ 105 pg/ml, and 25(OH) vitamin D >10 ng/ml. The multivariate Cox regression mortality risk adjusted to age, sex, CKD etiology, diabetes, smoking, cardiovascular comorbidity, blood pressure, proteinuria, eGFR, renin-angiotensin system blockers and vitamin D treatments, serum Ca, P, iPTH, and 25(OH) vitamin D (n = 964) showed that a higher mortality risk was associated with p > 4.00 mg/dl (HR 1.668, CI 95%: 1.201-2.317), iPTH >105 pg/ml (HR 1.386, CI 95%: 1.012-1.989), and 25(OH) vitamin D ≤ 10 ng/ml (HR 1.958, CI 95%: 1.238-3.098) and a lower mortality risk with 1,25(OH)2 vitamin D treatment (HR 0.639, CI 95%: 0.451-0.906). These data may contribute to the precise G3b-4 CKD-MBD biomarkers levels definition.
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Affiliation(s)
- Pablo Rios
- Comisión Asesora Programa de Salud Renal, Fondo Nacional de Recursos, Montevideo, Uruguay
| | - Ricardo Silvariño
- Comisión Asesora Programa de Salud Renal, Fondo Nacional de Recursos, Montevideo, Uruguay
- Facultad de Medicina, Universidad de la República, Montevideo, Uruguay
| | - Laura Sola
- Comisión Asesora Programa de Salud Renal, Fondo Nacional de Recursos, Montevideo, Uruguay
| | - Alejandro Ferreiro
- Comisión Asesora Programa de Salud Renal, Fondo Nacional de Recursos, Montevideo, Uruguay
- Facultad de Medicina, Universidad de la República, Montevideo, Uruguay
| | - Verónica Lamadrid
- Comisión Asesora Programa de Salud Renal, Fondo Nacional de Recursos, Montevideo, Uruguay
| | - Laura Fajardo
- Sociedad Uruguaya de Nefrología, Montevideo, Uruguay
| | - Liliana Gadola
- Comisión Asesora Programa de Salud Renal, Fondo Nacional de Recursos, Montevideo, Uruguay
- Facultad de Medicina, Universidad de la República, Montevideo, Uruguay
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Dlamini ST, Htet KM, Theint ECC, Li WM, Chang HW, Tu HP. Assessment of the Association of Vitamin D and the Risk of Tuberculosis among End-Stage Kidney Disease Population. Life (Basel) 2022; 12:life12111881. [PMID: 36431017 PMCID: PMC9699096 DOI: 10.3390/life12111881] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Revised: 11/11/2022] [Accepted: 11/11/2022] [Indexed: 11/16/2022] Open
Abstract
We investigated the role of vitamin D in the risk of tuberculosis (TB) among patients with end-stage kidney disease (ESKD). The retrospective cohort was conducted with data of 20,985 patients with kidney disease and 20,985 controls without kidney disease (1:1 matching on age of cohort entry and sex) in the duration of 1997−2010 from the Taiwan National Health insurance database. Then, by a case−cohort study, among 20,985 kidney disease, 3194 ESKD patients were identified with matched 3194 non-ESKD patients. Multivariate analyses revealed a significant association between kidney disease and tuberculosis (adjusted incidence rate ratio (IRR) 1.57 (1.33−1.86)), and the risk increased after 3 years of follow-up the (adjusted IRR 3.79 (2.55−5.62)), but after more years of follow-up no significance was observed. We also found that ESKD increases the risk of tuberculosis (adjusted IRR 3.67 (2.27−5.93)). However, vitamin D usage was not related with the tuberculosis risk in ESKD patients (p > 0.1783). Our study showed increased risk of tuberculosis in kidney disease and ESKD patients, and vitamin D was not beneficial in ESKD.
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Affiliation(s)
| | - Kyaw Moe Htet
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Ei Chue Chue Theint
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Wei-Ming Li
- Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
- Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Department of Urology, Ministry of Health and Welfare, Pingtung Hospital, Pingtung 900, Taiwan
| | - Hsin-Wen Chang
- Department of Applied Psychology, Hsuan Chuang University, 48 Hsuan Chuang Rd., Hsinchu City 30092, Taiwan
- Center for General Education, Hsuan Chuang University, Hsinchu City 30092, Taiwan
- Correspondence: (H.-W.C.); (H.-P.T.); Tel.: +886-3-5302255 (ext. 5222) (H.-W.C.)
| | - Hung-Pin Tu
- Department of Public Health and Environmental Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan
- Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
- Correspondence: (H.-W.C.); (H.-P.T.); Tel.: +886-3-5302255 (ext. 5222) (H.-W.C.)
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Abdalbary M, Sobh M, Elnagar S, Elhadedy MA, Elshabrawy N, Abdelsalam M, Asadipooya K, Sabry A, Halawa A, El-Husseini A. Management of osteoporosis in patients with chronic kidney disease. Osteoporos Int 2022; 33:2259-2274. [PMID: 35748896 DOI: 10.1007/s00198-022-06462-3] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 05/31/2022] [Indexed: 12/19/2022]
Abstract
Patients with CKD have a 4-fivefold higher rate of fractures. The incidence of fractures increases with deterioration of kidney function. The process of skeletal changes in CKD patients is characterized by compromised bone strength because of deterioration of bone quantity and/or quality. The fractures lead to a deleterious effect on the quality of life and higher mortality in patients with CKD. The pathogenesis of bone loss and fracture is complex and multi-factorial. Renal osteodystrophy, uremic milieu, drugs, and systemic diseases that lead to renal failure all contribute to bone damage in CKD patients. There is no consensus on the optimal diagnostic method of compromised bone assessment in patients with CKD. Bone quantity and mass can be assessed by dual-energy x-ray absorptiometry (DXA) or quantitative computed tomography (QCT). Bone quality on the other side can be assessed by non-invasive methods such as trabecular bone score (TBS), high-resolution bone imaging methods, and invasive bone biopsy. Bone turnover markers can reflect bone remodeling, but some of them are retained by kidneys. Understanding the mechanism of bone loss is pivotal in preventing fracture in patients with CKD. Several non-pharmacological and therapeutic interventions have been reported to improve bone health. Controlling laboratory abnormalities of CKD-MBD is crucial. Anti-resorptive therapies are effective in improving BMD and reducing fracture risk, but there are uncertainties about safety and efficacy especially in advanced CKD patients. Accepting the prevalent of low bone turnover in patients with advanced CKD, the osteo-anabolics are possibly promising. Parathyroidectomy should be considered a last resort for intractable cases of renal hyperparathyroidism. There is a wide unacceptable gap in osteoporosis management in patients with CKD. This article is focusing on the updated management of CKD-MBD and osteoporosis in CKD patients. Chronic kidney disease deteriorates bone quality and quantity. The mechanism of bone loss mainly determines pharmacological treatment. DXA and QCT provide information about bone quantity, but assessing bone quality, by TBS, high-resolution bone imaging, invasive bone biopsy, and bone turnover markers, can guide us about the mechanism of bone loss.
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Affiliation(s)
- M Abdalbary
- Mansoura Nephrology and Dialysis Unit, Mansoura University, Mansoura, Egypt
- Division of Nephrology, Bone and Mineral Metabolism, University of Kentucky, 800 Rose Street, Room MN-560, Lexington, KY, 40536-0298, USA
| | - M Sobh
- Mansoura Nephrology and Dialysis Unit, Mansoura University, Mansoura, Egypt
| | - S Elnagar
- Mansoura Nephrology and Dialysis Unit, Mansoura University, Mansoura, Egypt
| | - M A Elhadedy
- Nephrology and Transplantation Unit, Mansoura Urology and Nephrology Center, Mansoura, Egypt
| | - N Elshabrawy
- Mansoura Nephrology and Dialysis Unit, Mansoura University, Mansoura, Egypt
| | - M Abdelsalam
- Mansoura Nephrology and Dialysis Unit, Mansoura University, Mansoura, Egypt
| | - K Asadipooya
- Division of Endocrinology, University of Kentucky, Lexington, USA
| | - A Sabry
- Mansoura Nephrology and Dialysis Unit, Mansoura University, Mansoura, Egypt
| | - A Halawa
- Sheffield Teaching Hospital, University of Liverpool, Liverpool, UK
| | - A El-Husseini
- Division of Nephrology, Bone and Mineral Metabolism, University of Kentucky, 800 Rose Street, Room MN-560, Lexington, KY, 40536-0298, USA.
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Bishop CW, Strugnell SA, Csomor P, Kaiser E, Ashfaq A. Extended-Release Calcifediol Effectively Raises Serum Total 25-Hydroxyvitamin D Even in Overweight Nondialysis Chronic Kidney Disease Patients with Secondary Hyperparathyroidism. Am J Nephrol 2022; 53:446-454. [PMID: 35551374 PMCID: PMC9393814 DOI: 10.1159/000524289] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 03/19/2022] [Indexed: 12/15/2022]
Abstract
INTRODUCTION Obesity increases the risk of vitamin D insufficiency, which exacerbates secondary hyperparathyroidism in chronic kidney disease. Recent studies suggest that serum total 25-hydroxyvitamin D (25OHD) levels of ≥50 ng/mL are necessary to produce significant reductions in elevated parathyroid hormone levels in nondialysis patients. Data from real-world and randomized controlled trials (RCTs) involving these patients were examined for (1) relationships between vitamin D treatments and the achieved levels of serum 25OHD and between serum 25OHD and body weight (BW)/body mass index (BMI); and (2) the impact of BW/BMI on achieving serum 25OHD levels ≥50 ng/mL with extended-release calcifediol (ERC) treatment or vitamin D supplementation (cholecalciferol or ergocalciferol). METHODS Data obtained from nondialysis patients participating in two real-world studies, one conducted in Europe (Study 1) and the other (Study 2) in the USA, and in two US RCTs (Studies 3 and 4) were analyzed for serum 25OHD outcomes after treatment with ERC, vitamin D supplements, or placebo. RESULTS More than 50% of subjects treated with vitamin D supplements in both real-world studies (Studies 1 and 2) failed to achieve serum 25OHD levels ≥30 ng/mL, a level widely viewed by nephrologists as the threshold of adequacy; only 7.3-7.5% of subjects achieved levels ≥50 ng/mL. Data from the European study (Study 1) showed that serum 25OHD levels had significant and nearly identical inverse relationships with BW and BMI, indicating that high BW or BMI thwarts the ability of vitamin D supplements to raise serum 25OHD. One RCT (Study 3) showed that 8 weeks of ERC treatment (60 μg/day) raised serum 25OHD levels to ≥30 and 50 ng/mL in all subjects, regardless of BW, while cholecalciferol (300,000 IU/month) raised serum 25OHD to these thresholds in 56% and 0% of subjects, respectively. The other RCT (Study 4) showed that ERC treatment (30 or 60 μg/day) successfully raised mean serum 25OHD levels to at least 50 ng/mL for subjects in all BW categories, whereas no increases were observed with placebo treatment. CONCLUSION Real-world studies conducted in Europe and USA in nondialysis patients (Studies 1 and 2) showed that vitamin D supplements (cholecalciferol or ergocalciferol) were unreliable in raising serum total 25OHD to targets of 30 or 50 ng/mL. In contrast, ERC was demonstrated to be effective in one real-world study (Study 2) and two RCTs (Studies 3 and 4) conducted in US nondialysis patients in raising serum 25OHD to these targeted levels irrespective of BW.
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Affiliation(s)
| | | | | | | | - Akhtar Ashfaq
- Renal Division, OPKO Health, Inc., Miami, Florida, USA
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Ureña Torres PA, Souberbielle JC, Solal MC. Bone Fragility in Chronic Kidney Disease Stage 3 to 5: The Use of Vitamin D Supplementation. Metabolites 2022; 12:metabo12030266. [PMID: 35323709 PMCID: PMC8953916 DOI: 10.3390/metabo12030266] [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: 02/21/2022] [Revised: 03/10/2022] [Accepted: 03/17/2022] [Indexed: 12/02/2022] Open
Abstract
Frequently silent until advanced stages, bone fragility associated with chronic kidney disease-mineral and bone disease (CKD-MBD) is one of the most devastating complications of CKD. Its pathophysiology includes the reduction of active vitamin D metabolites, phosphate accumulation, decreased intestinal calcium absorption, renal alpha klotho production, and elevated fibroblast growth factor 23 (FGF23) levels. Altogether, these factors contribute firstly to secondary hyperparathyroidism, and ultimately, to micro- and macrostructural bone changes, which lead to low bone mineral density and an increased risk of fracture. A vitamin D deficiency is common in CKD patients, and low circulating 25(OH)D levels are invariably associated with high serum parathyroid hormone (PTH) levels as well as with bone mineralization defects, such as osteomalacia in case of severe forms. It is also associated with a variety of non-skeletal diseases, including cardiovascular disease, diabetes mellitus, multiple sclerosis, cancer, and reduced immunological response. Current international guidelines recommend supplementing CKD patients with nutritional vitamin D as in the general population; however, there is no randomized clinical trial (RCT) evaluating the effect of vitamin D (or vitamin D+calcium) supplementation on the risk of fracture in the setting of CKD. It is also unknown what level of circulating 25(OH)D would be sufficient to prevent bone abnormalities and fractures in these patients. The impact of vitamin D supplementation on other surrogate endpoints, including bone mineral density and bone-related circulating biomarkers (PTH, FGF23, bone-specific alkaline phosphatase, sclerostin) has been evaluated in several RTCs; however, the results were not always translated into an improvement in long-term outcomes, such as reduced fracture risk. This review provides a brief and comprehensive update on CKD-related bone fragility and the use of natural vitamin D supplementation in these patients.
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Affiliation(s)
- Pablo Antonio Ureña Torres
- Department of Dialysis AURA Nord Saint Ouen, 12, Rue Anselme, 93400 Saint Ouen, France
- Department of Renal Physiology, Necker Hospital, University of Paris Descartes, 75015 Paris, France;
- Correspondence: (P.A.U.T.); (M.C.S.)
| | - Jean Claude Souberbielle
- Department of Renal Physiology, Necker Hospital, University of Paris Descartes, 75015 Paris, France;
| | - Martine Cohen Solal
- Bioscar INSERM U1132, Department of Rheumatology, Université de Paris, Hôpital Lariboisière, 75010 Paris, France
- Correspondence: (P.A.U.T.); (M.C.S.)
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McKnite AM, Job KM, Nelson R, Sherwin CM, Watt KM, Brewer SC. Medication based machine learning to identify subpopulations of pediatric hemodialysis patients in an electronic health record database. INFORMATICS IN MEDICINE UNLOCKED 2022; 34. [PMID: 36405250 PMCID: PMC9674326 DOI: 10.1016/j.imu.2022.101104] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Electronic health records (EHRs) have given rise to large and complex databases of medical information that have the potential to become powerful tools for clinical research. However, differences in coding systems and the detail and accuracy of the information within EHRs can vary across institutions. This makes it challenging to identify subpopulations of patients and limits the widespread use of multi-institutional databases. In this study, we leveraged machine learning to identify patterns in medication usage among hospitalized pediatric patients receiving renal replacement therapy and created a predictive model that successfully differentiated between intermittent (iHD) and continuous renal replacement therapy (CRRT) hemodialysis patients. We trained six machine learning algorithms (logistical regression, Naïve Bayes, k-nearest neighbor, support vector machine, random forest, and gradient boosted trees) using patient records from a multi-center database (n = 533) and prescribed medication ingredients (n = 228) as features to discriminate between the two hemodialysis types. Predictive skill was assessed using a 5-fold cross-validation, and the algorithms showed a range of performance from 0.7 balanced accuracy (logistical regression) to 0.86 (random forest). The two best performing models were further tested using an independent single-center dataset and achieved 84–87% balanced accuracy. This model overcomes issues inherent within large databases and will allow us to utilize and combine historical records, significantly increasing population size and diversity within both iHD and CRRT populations for future clinical studies. Our work demonstrates the utility of using medications alone to accurately differentiate subpopulations of patients in large datasets, allowing codes to be transferred between different coding systems. This framework has the potential to be used to distinguish other subpopulations of patients where discriminatory ICD codes are not available, permitting more detailed insights and new lines of research.
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Abstract
The COVID-19 pandemic has generated high interest in factors modulating risk of infection, disease severity and recovery. Vitamin D has received interest since it is known to modulate immune function and vitamin D deficiency is associated with increased risk of respiratory infections and adverse health outcomes in severely ill patients. There are no population representative data on the direct relationship between vitamin D status and SARS-CoV-2 infection risk and severity of COVID-19. Data from intervention studies are limited to 4 studies. Here we summarise findings regarding vitamin D status and metabolism and their alterations during severe illness, relevant to COVID-19 patients. Further, we summarise vitamin D intervention studies with respiratory disease outcomes and in critically ill patients and provide an overview of relevant patient and population guidelines. Vitamin D deficiency is highly prevalent in hospitalised patients, particularly when critically ill including those with COVID-19. Acute and critical illness leads to pronounced changes in vitamin D metabolism and status, suggestive of increased requirements. This needs to be considered in the interpretation of potential links between vitamin D status and disease risk and severity and for patient management. There is some evidence that vitamin D supplementation decreases the risk of respiratory tract infections, while supplementation of ICU patients has shown little effect on disease severity or length of treatment. Considering the high prevalence of deficiency and low risks associated with supplementation, pro-actively applying current population and patient management guidelines to prevent, monitor and correct vitamin D deficiency is appropriate.
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