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Khairallah P, Cortez NE, McMahon DJ, Sammons S, Agarwal S, Crew RJ, Cohen DJ, Dube GK, Mohan S, Chang JH, Morris HK, Fernandez HE, Aponte MA, Adebayo AO, Aghi A, Zaninotto M, Plebani M, Tripepi G, Gallieni M, Cosma C, Fusaro M, Nickolas TL. Calcitriol supplementation after kidney transplantation: results of a double-blinded, randomized, placebo-controlled trial. J Bone Miner Res 2025; 40:603-616. [PMID: 40089990 PMCID: PMC12103722 DOI: 10.1093/jbmr/zjaf044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Revised: 02/12/2025] [Accepted: 02/28/2025] [Indexed: 03/18/2025]
Abstract
A significant number of kidney transplant recipients have low BMD. We hypothesized that calcitriol administration over the first year posttransplantation would protect the cortical skeleton in recipients managed without corticosteroids by suppressing PTH and bone remodeling. In this double-blind, placebo-controlled trial, 67 participants aged ≥18 yr on corticosteroid-sparing immunosuppressive regimen were randomized to daily calcitriol 0.5 μg or placebo for 12 mo after transplantation. The primary endpoint was the percent change in cortical density at the radius and tibia from pre- to postcalcitriol treatment compared to placebo as measured by HR-pQCT. Areal BMD was measured by DXA. Cortical and trabecular volumetric BMD and microarchitecture and total estimated bone strength were measured by HR-pQCT. Blood samples for bone metabolic markers were obtained at baseline, 1- and 12 mo. All primary analyses were intent to treat. Safety was assessed for hypercalcemia and progression of vascular calcifications. Thirty-two participants received calcitriol and 29 received placebo; 27 and 27 participants completed the study, respectively. Most participants were male and Caucasian. Baseline Z-scores at all sites were within 0.5 SD of the general population. At 12 mo posttransplantation, there were no between-group differences in areal BMD, volumetric BMD, microarchitecture or bone strength, or serum levels of bone markers. Participants with versus without bone loss had a blunted anabolic response over 12 mo measured by serum bone markers. Hypercalcemia was higher in the calcitriol group compared to placebo (p < .001). No changes in arterial calcification scores were observed. In this randomized placebo-controlled study of calcitriol administration in kidney transplant recipients on corticosteroid-sparing immunosuppression, calcitriol did not improve bone quality and strength but was associated with higher rates of hypercalcemia.
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Affiliation(s)
- Pascale Khairallah
- Department of Medicine, University of California, San Francisco, CA, 94110, United States
| | - Natalia E Cortez
- Department of Clinical and Biological Sciences, University of Turin, Turin, 10124, Italy
| | - Donald J McMahon
- Department of Medicine, Columbia University, New York, NY, 10032, United States
| | - Stephen Sammons
- Department of Internal Medicine, Division of Nephrology and Hypertension, University of Utah, Salt Lake City, UT, 84112, United States
| | - Sanchita Agarwal
- Department of Medicine, Columbia University, New York, NY, 10032, United States
| | - R John Crew
- Department of Medicine, Columbia University, New York, NY, 10032, United States
| | - David J Cohen
- Department of Medicine, Columbia University, New York, NY, 10032, United States
| | - Geoffrey K Dube
- Department of Medicine, Columbia University, New York, NY, 10032, United States
| | - Sumit Mohan
- Department of Medicine, Columbia University, New York, NY, 10032, United States
| | - Jae-Hyung Chang
- Department of Medicine, Columbia University, New York, NY, 10032, United States
| | - Heather K Morris
- Department of Medicine, Columbia University, New York, NY, 10032, United States
| | - Hilda E Fernandez
- Department of Medicine, Columbia University, New York, NY, 10032, United States
| | | | | | | | - Martina Zaninotto
- QI.LAB.MED, Spin-off of the University of Padova, Padua, 35122, Italy
| | - Mario Plebani
- Department of Medicine, University of Padova, Padua, 35122, Italy
| | - Giovanni Tripepi
- National Research Council (CNR), Institute of Clinical Physiology (IFC), Pisa, 56124, Italy
| | - Maurizio Gallieni
- Department of Biomedical and Clinical Sciences, University of Milano, Milan, 20157, Italy
| | - Chiara Cosma
- Department of Medicine, University of Padova, Padua, 35122, Italy
| | - Maria Fusaro
- Department of Medicine, University of Padova, Padua, 35122, Italy
- National Research Council (CNR), Institute of Clinical Physiology (IFC), Pisa, 56124, Italy
| | - Thomas L Nickolas
- Division of Bone and Mineral Diseases, Washington University, St. Louis, MO 63110, United States
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2
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Schneider S, Biggerstaff D, Barber TM. Dietary Guidelines Post Kidney Transplant: Is This the Missing Link in Recovery and Graft Survival? Transpl Int 2025; 38:14288. [PMID: 40248508 PMCID: PMC12004285 DOI: 10.3389/ti.2025.14288] [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: 01/02/2025] [Accepted: 03/11/2025] [Indexed: 04/19/2025]
Abstract
The physiology of a transplanted kidney is affected from the moment it is separated from the donor. The risk of complications arising from surgery are highly associated with ischemic-reperfusion injury (IRI) due to the effects of hypoxia and oxidative stress during the procurement, preservation and reperfusion procedures. Hypoxia promotes the formation of reactive oxygen species (ROS) and it seems apparent that finding ways of optimising the metabolic milieu for the transplanted kidney would improve recovery and graft survival. Studies have demonstrated the benefits of nutrition and antioxidant compounds in mitigating the disturbance of energy supply to cells post-transplant and at improving long-term graft survival. Particularly in patients who may be nutritionally deficient following long-term dialysis. Despite the high incidence of allograft failure, a search of the literature and grey literature reveals no medical nutriti on therapy guidelines on beneficial nutrient intake to aid transplant recovery and survival. This narrative review aims to summarise current knowledge of specific macro and micronutrients and their effect on allograft recovery and survival in the perioperative period, up to 1-year post transplant, to optimise the metabolic environment and mitigate risk to graft injury.
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Affiliation(s)
- Suzanne Schneider
- Directorate Applied Health, Warwick Medical School, University of Warwick, Coventry, United Kingdom
| | - Deborah Biggerstaff
- Directorate Applied Health, Warwick Medical School, University of Warwick, Coventry, United Kingdom
| | - Thomas M. Barber
- Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, United Kingdom
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire, Coventry, United Kingdom
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3
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Kotowska K, Wojciuk B, Sieńko J, Bogacz A, Stukan I, Drożdżal S, Czerny B, Tejchman K, Trybek G, Machaliński B, Kotowski M. The Role of Vitamin D Metabolism Genes and Their Genomic Background in Shaping Cyclosporine A Dosage Parameters after Kidney Transplantation. J Clin Med 2024; 13:4966. [PMID: 39201108 PMCID: PMC11355102 DOI: 10.3390/jcm13164966] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 08/12/2024] [Accepted: 08/19/2024] [Indexed: 09/02/2024] Open
Abstract
Background: Kidney transplantation is followed by immunosuppressive therapy involving calcineurin inhibitors (CNIs) such as cyclosporin A. However, long-term high CNIs doses can lead to vitamin D deficiency, and genetic variations influencing vitamin D levels can indirectly impact the necessary CNIs dosage. This study investigates the impact of genetic variations of vitamin D binding protein (DBP) rs2282679 and CYP2R1 hydroxylase rs10741657 polymorphisms on the cyclosporin A dosage in kidney transplant recipients. Additional polymorphisims of genes that are predicted to influence the pharmacogenetic profile were included. Methods: Gene polymorphisms in 177 kidney transplant recipients were analyzed using data mining techniques, including the Random Forest algorithm and Classification and Regression Trees (C&RT). The relationship between the concentration/dose (C/D) ratio of cyclosporin A and genetic profiles was assessed to determine the predictive value of DBP rs2282679 and CYP2R1 rs10741657 polymorphisms. Results: Polymorphic variants of the DBP (rs2282679) demonstrated a strong predictive value for the cyclosporin A C/D ratio in post-kidney transplantation patients. By contrast, the CYP2R1 polymorphism (rs10741657) did not show predictive significance. Additionally, the immune response genes rs231775 CTLA4 and rs1800896 IL10 were identified as predictors of cyclosporin A response, though these did not result in statistically significant differences. Conclusions:DBP rs2282679 polymorphisms can significantly predict the cyclosporin A C/D ratio, potentially enhancing the accuracy of CNI dosing. This can help identify patient groups at risk of vitamin D deficiency, ultimately improving the management of kidney transplant recipients. Understanding these genetic influences allows for more personalized and effective treatment strategies, contributing to better long-term outcomes for patients.
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Affiliation(s)
- Katarzyna Kotowska
- Clinic of Maxillofacial Surgery, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland
| | - Bartosz Wojciuk
- Department of Immunological Diagnostics, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland
| | - Jerzy Sieńko
- Institute of Physical Culture Sciences, University of Szczecin, 70-453 Szczecin, Poland
| | - Anna Bogacz
- Department of Personalized Medicine and Cell Therapy, Regional Blood Center, 60-354 Poznan, Poland
| | - Iga Stukan
- Department of General Pathology, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland
| | - Sylwester Drożdżal
- Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland
| | - Bogusław Czerny
- Department of General Pharmacology and Pharmacoeconomics, Pomeranian Medical University in Szczecin, 71-210 Szczecin, Poland
| | - Karol Tejchman
- Department of General Surgery and Transplantation, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland
| | - Grzegorz Trybek
- Department of Interdisciplinary Dentistry, Pomeranian Medical University, 70-204 Szczecin, Poland
| | - Bogusław Machaliński
- Department of General Pathology, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland
| | - Maciej Kotowski
- Department of General Surgery and Transplantation, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland
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Buyukdemirci S, Oguz EG, Cimen SG, Sahin H, Cimen S, Ayli MD. Vitamin D deficiency may predispose patients to increased risk of kidney transplant rejection. World J Transplant 2022; 12:299-309. [PMID: 36187881 PMCID: PMC9516489 DOI: 10.5500/wjt.v12.i9.299] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Revised: 06/01/2022] [Accepted: 09/07/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Vitamin D deficiency occurs in more than 80% of kidney transplant recipients. Its immunomodulatory effects can predispose transplant recipients to rejection and chronic allograft nephropathy (CAN). This study determined the association between serum 25 (OH) vitamin D, biopsy-proven allograft rejection, and CAN rates.
AIM To determine the relationship between serum 25 (OH) vitamin D level and biopsy-proven allograft rejection and CAN rate in renal transplant recipients.
METHODS Adult renal transplant recipients followed at the clinic between January 2013 and 2018 were included. Recipients requiring graft biopsy due to declined function, hematuria, and proteinuria were reviewed. The two groups were compared regarding collected data, including the biopsy results, immunologic parameters, vitamin D, parathyroid hormone (PTH), phosphorus, albumin levels, and graft function tests.
RESULTS Fifty-two recipients who underwent graft biopsy met the inclusion criteria. In all, 14 recipients had a vitamin D level > 15 ng/mL (group 1) vs ≤ 15 ng/mL (group 2) in 38. In total, 27 patients had biopsy-proven rejection, and 19 had CAN. There was only 1 recipient with biopsy-proven rejection in group 1, whereas there were 24 patients with rejection in group 2. The rejection rate was significantly higher in group 2 than in group 1 (P < 0.001). Four patients were diagnosed with CAN in group 1 vs fifteen in group 2. There was no significant difference in the CAN rate between the two groups. PTH was higher at the time of graft biopsy (P = 0.009, P = 0.022) in group 1 with a mean of 268 pg/mL. Donor-specific antibodies were detected in 14 (56.0%) of the recipients with rejection. Vitamin D level was 9.7 ± 3.4 ng/mL in the rejection group vs 14.7 ± 7.2 in the non-rejection group; this difference was statistically significant (P = 0.003). The albumin levels were significantly lower in patients with rejection than in those without rejection (P = 0.001). In univariate regression analysis of risk factors affecting rejection, sex, serum vitamin D, phosphorus and albumin were found to have an impact (P = 0.027, P = 0.007, P = 0.023, P = 0.008). In multivariate regression analysis, the same factors did not affect rejection.
CONCLUSION The serum 25 (OH) vitamin D level in kidney transplant recipients remained low. Although low serum vitamin D level emerged as a risk factor for rejection in univariate analysis, this finding was not confirmed by multivariate analysis. Prospective studies are required to determine the effect of serum vitamin D levels on allograft rejection.
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Affiliation(s)
- Semih Buyukdemirci
- Department of Internal Medicine, Sağlık Bilimleri Universitesi, Ankara 65000, Altındağ, Turkey
| | - Ebru Gok Oguz
- Department of Nephrology, Sağlık Bilimleri Universitesi, Ankara 65000, Altındağ, Turkey
| | - Sanem Guler Cimen
- Department of General Surgery, Sağlık Bilimleri Universitesi, Ankara 65000, Altındağ, Turkey
| | - Hatice Sahin
- Department of Nephrology, Sağlık Bilimleri Universitesi, Ankara 65000, Altındağ, Turkey
| | - Sertac Cimen
- Department of Urology, Sağlık Bilimleri Universitesi, Ankara 65000, Altındağ, Turkey
| | - Mehmet Deniz Ayli
- Department of Nephrology, Sağlık Bilimleri Universitesi, Ankara 65000, Altındağ, Turkey
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5
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Wang L, Cheng H, Zou X, Yuan J, Wu W, Han S, Wang J, Zhang L, He K, Zhao MH, Wang X. Prevalence and Correlates of Cardiovascular Calcification and Its Prognostic Effects Among Patients With Chronic Kidney Disease: Results From the C-STRIDE Study. Front Public Health 2022; 9:762370. [PMID: 35071158 PMCID: PMC8771912 DOI: 10.3389/fpubh.2021.762370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Accepted: 12/08/2021] [Indexed: 11/16/2022] Open
Abstract
Background and Aims: The purpose of this study was to identify the characteristics and risk factors for cardiovascular calcification, and its relationship to prognosis, in patients with chronic kidney disease (CKD) stages 1–4. Methods: Cardiovascular calcification was evaluated at baseline by lateral abdominal radiography to detect abdominal aortic calcifications (AAC), and by echocardiogram to detect cardiac valvular calcifications (CVC), respectively. Demographic and laboratory data were collected and analyzed. Univariate and multivariable logistic regression model was used to explore the factors associated with the indicators of cardiovascular calcification, while Cox proportional hazards regression was used to examine the association between AAC/CVC and incidence of cardiovascular events and all-cause mortality. Results: A subgroup of 2,235 patients with measurement of AAC in the C-STRIDE study and a subgroup of 2,756 patients with CVC were included in the analysis. AAC was present in 206 patients (9.22%) and CVC was present in 163 patients (5.91%). Age, gender, history of cardiovascular diseases, smoking, hypertension, diabetes, levels of hemoglobin, low-density lipoprotein cholesterol, and uric acid were associated with prevalence of AAC, while only age, history of cardiovascular diseases, levels of serum albumin and low-density lipoprotein cholesterol were associated with prevalence of CVC (all p < 0.05).Survival analyses showed that cardiovascular events and all-cause mortality were significantly greater in patients with AACor with CVC (all p-values for log-rank tests <0.05). After adjustment for age, sex and estimated glomerular filtration rate (eGFR), AAC was associated with increased risk of all-cause mortality (hazard ratio = 1.67[95% confidence interval: 0.99, 2.79]), while CVC associated with that of cardiovascular events only among patients with comparatively normal eGFR (≥45 ml/min/1.73m2) (hazard ratio = 1.99 [0.98, 4.03]). Conclusion: Demographic and traditional cardiovascular risk factors were associated with cardiovascular calcification, especially AAC. AAC may be associated with risk of death for patients CKD of any severity, while CVC as a possible risk factor for cardiovascular disease only among those with mild to moderate CKD. Assessments of vascular calcification are need to be advanced to patients in the early and middle stages of chronic kidney disease and to initiate appropriate preventive measures earlier.
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Affiliation(s)
- Lan Wang
- The First Clinical College, Hubei University of Chinese Medicine, Wuhan, China.,Institute of Chinese Medicine Nephrology, Hubei Provincial Hospital of TCM, Hubei Province Academy of Traditional Chinese Medicine, Wuhan, China
| | - Hong Cheng
- Institute of Chinese Medicine Nephrology, Hubei Provincial Hospital of TCM, Hubei Province Academy of Traditional Chinese Medicine, Wuhan, China
| | - Xinrong Zou
- Institute of Chinese Medicine Nephrology, Hubei Provincial Hospital of TCM, Hubei Province Academy of Traditional Chinese Medicine, Wuhan, China
| | - Jun Yuan
- The First Clinical College, Hubei University of Chinese Medicine, Wuhan, China.,Institute of Chinese Medicine Nephrology, Hubei Provincial Hospital of TCM, Hubei Province Academy of Traditional Chinese Medicine, Wuhan, China
| | - Wenjing Wu
- The First Clinical College, Hubei University of Chinese Medicine, Wuhan, China.,Institute of Chinese Medicine Nephrology, Hubei Provincial Hospital of TCM, Hubei Province Academy of Traditional Chinese Medicine, Wuhan, China
| | - Siping Han
- Institute of Chinese Medicine Nephrology, Hubei Provincial Hospital of TCM, Hubei Province Academy of Traditional Chinese Medicine, Wuhan, China
| | - Jinwei Wang
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.,Institute of Nephrology, Peking University, Beijing, China.,Key Laboratory of Renal Disease, National Health Commission of China, Beijing, China.,Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China.,Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China
| | - Luxia Zhang
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.,Institute of Nephrology, Peking University, Beijing, China.,Key Laboratory of Renal Disease, National Health Commission of China, Beijing, China.,Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China.,Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China.,National Institute of Health Data Science at Peking University, Beijing, China
| | - Kevin He
- Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, United States
| | - Ming-Hui Zhao
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.,Institute of Nephrology, Peking University, Beijing, China.,Key Laboratory of Renal Disease, National Health Commission of China, Beijing, China.,Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China.,Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China.,Peking-Tsinghua Center for Life Sciences, Beijing, China
| | - Xiaoqin Wang
- Institute of Chinese Medicine Nephrology, Hubei Provincial Hospital of TCM, Hubei Province Academy of Traditional Chinese Medicine, Wuhan, China
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6
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Abstract
After kidney transplantation, mineral and bone disorders are associated with higher risk of fractures and consequent morbidity and mortality. Disorders of calcium and phosphorus, vitamin D deficiency, and hyperparathyroidism are also common. The epidemiology of bone disease has evolved over the past several decades due to changes in immunosuppressive regimens, mainly glucocorticoid minimization or avoidance. The assessment of bone disease in kidney transplant recipients relies on risk factor recognition and bone mineral density assessment. Several drugs have been trialed for the treatment of post-transplant mineral and bone disorders. This review will focus on the epidemiology, effect, and treatment of metabolic and skeletal derangements in the transplant recipient.
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Affiliation(s)
- Pascale Khairallah
- Section of Nephrology and Selzman Institute for Kidney Health, Baylor College of Medicine, Houston, Texas
| | - Thomas L. Nickolas
- Division of Nephrology, Columbia University Irving Medical Center, New York, New York
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7
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Bucharles SGE, Barreto FC, Oliveira RBD. Hypovitaminosis D in chronic kidney disease. J Bras Nefrol 2021; 43:639-644. [PMID: 34910798 PMCID: PMC8823918 DOI: 10.1590/2175-8239-jbn-2021-s106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 07/02/2021] [Indexed: 11/22/2022] Open
Affiliation(s)
- Sérgio Gardano Elias Bucharles
- Universidade Federal do Paraná, Medical Clinic Department, Service of Nephrology, Curitiba, PR, Brazil.,Universidade Federal do Paraná, Hospital de Clínicas Complex, Service of Nephrology, Curitiba, PR, Brazil
| | - Fellype Carvalho Barreto
- Universidade Federal do Paraná, Medical Clinic Department, Service of Nephrology, Curitiba, PR, Brazil.,Universidade Federal do Paraná, Hospital de Clínicas Complex, Service of Nephrology, Curitiba, PR, Brazil
| | - Rodrigo Bueno de Oliveira
- Universidade de Campinas, Faculdade de Ciências Médicas, Medical Clinic Department, Service of Nephrology, Campinas, SP, Brazil
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8
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Xi Y, Ma Y, Xie B, Di A, Xu S, Luo X, Wang C, Dai H, Yan G, Qi Z. Vitamin D3 combined with antibody agents suppresses alloreactive memory T-cell responses to induce heart allograft long-term survival. Transpl Immunol 2021; 66:101374. [PMID: 33592299 DOI: 10.1016/j.trim.2021.101374] [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: 01/22/2021] [Revised: 02/11/2021] [Accepted: 02/11/2021] [Indexed: 10/22/2022]
Abstract
BACKGROUND The pre-stored memory T cells in organ transplant patient carry a high risk of allograft rejection. The current study aimed to determine whether the allogenic response of adoptively transferred memory T cells in mice was suppressed by vitamin D3 monotherapy alone or in combination with monoclonal antibody treatment. METHODS Prior to vascularized heterotopic heart transplantation, naïve C57BL/6 mice were primed with memory T cells. Recipient mice were administered vitamin D3 alone or in combination with monoclonal antibodies (anti-CD40L/ anti-LFA-1). Memory T cells and CD4+ forkhead box P3+ T cells in recipient spleens were measured using flow cytometry. Additionally, the expression of cytokines was measured by ELISA and quantitative PCR. Inflammatory factors in the grafts were identified by hematoxylin and eosin staining. RESULTS Vitamin D3 in conjunction with anti-CD40L/ anti-LFA-1 antibodies were administered according to the median survival time from 6.5 to 80 days. The results revealed that grafts were protected through the prevention of inflammatory cell infiltration. Combined treatment decreased the mRNA levels of IL-2, IFN-γ and IL-10 and increased the mRNA levels of IL-4, Foxp3 and TGF-β in the allograft. Rejection was suppressed by a reduction of CD4+CD44high CD62L+ and CD8+ CD44high CD62L+ memory T cells, the induction of regulatory T cells in the recipient spleen and a reduction of serum IL-2, IFN-γ and IL-10 levels. CONCLUSION Vitamin D3 efficiently protected allografts from memory T-cell allo-responses when combined with anti-CD40L/anti-LFA-1 antibodies therapy.
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Affiliation(s)
- Yanfeng Xi
- Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, School of Medicine, Xiamen University, Xiamen, Fujian, China; The tumor hospital of Chang Zhou, Chang Zhou, Jiangsu, China
| | - Yunhan Ma
- Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Baiyi Xie
- Department of Urology Surgery, Ruikang Hospital affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Anjie Di
- Basic Medical Department of Medical College, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Shuangyue Xu
- Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Xuewei Luo
- Medicinal College, Guangxi University, Nanning, Guangxi, China
| | - Chenxi Wang
- Basic Medical Department of Medical College, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Helong Dai
- Department of Kidney Transplantation, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China; Clinical Research Center for Organ Transplantation in Hunan Province, Changsha, Hunan, China; Clinical Immunology Center, Central South University, Changsha, Hunan 410000, China.
| | - Guoliang Yan
- Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, School of Medicine, Xiamen University, Xiamen, Fujian, China; Basic Medical Department of Medical College, School of Medicine, Xiamen University, Xiamen, Fujian, China.
| | - Zhongquan Qi
- Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, School of Medicine, Xiamen University, Xiamen, Fujian, China; Medicinal College, Guangxi University, Nanning, Guangxi, China.
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9
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Gariazzo L, Gasparini G, Casabella A, Carmisciano L, Clapasson A, Murgioni F, Molfetta L, Cozzani E, Parodi A. Is ultraviolet radiation avoidance affecting bone health in melanoma patients? PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE 2021; 37:329-333. [PMID: 33432678 DOI: 10.1111/phpp.12657] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Revised: 12/21/2020] [Accepted: 01/06/2021] [Indexed: 11/29/2022]
Abstract
BACKGROUND Ultraviolet (UV) radiation has numerous beneficial effects on human health, including stimulating vitamin D and serotonin production and immuno-regulatory activities. Conversely, UV radiation is also classified as a group one carcinogen by the International Agency for Research on Cancer. PURPOSE To investigated the effects of UV radiation avoidance in melanoma patients in terms of vitamin D levels but also of bone mineral density and trabecular bone microarchitecture. METHODS We conducted an observational study investigating the effects of UV radiation avoidance in 31 melanoma patients in terms of vitamin D levels but also of bone mineral density and trabecular bone microarchitecture by using dual-energy X-ray absorptiometry scan. Data were compared with two control groups of healthy subjects, who were chronically exposed or not exposed to UV radiation during their lifetime. RESULTS Melanoma patients had on average slightly lower levels of vitamin D, without reaching statistical significance (P = .135). No significant difference was found across the three groups on T-scores of femoral neck (P = .544), of total hip (P = .617) and of lumbar spine P = .155). No significant difference was found on and trabecular bone score across exposure groups (P = .895). CONCLUSION UV radiation avoidance does not seem to significantly impact vitamin D levels nor bone health in melanoma patients. Thus, UV protective behavior is advisable for all melanoma patients.
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Affiliation(s)
- Lodovica Gariazzo
- Section of Dermatology, Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy.,Dermatology Unit, Ospedale Policlinico San Martino IRCCS, Genoa, Italy
| | - Giulia Gasparini
- Section of Dermatology, Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy.,Dermatology Unit, Ospedale Policlinico San Martino IRCCS, Genoa, Italy.,Department of Experimental Medicine (DIMES), University of Genoa, Genoa, Italy
| | - Andrea Casabella
- University of Genoa, School of Medical and Pharmaceutical Sciences, Research Centre of Ostoeporosis and osteoarticular disease Di.M.I., Policlinic hospital San Martino, Genoa, Italy
| | - Luca Carmisciano
- Section of Biostatistics, Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy
| | - Andrea Clapasson
- Dermatology Unit, Ospedale Policlinico San Martino IRCCS, Genoa, Italy
| | - Franca Murgioni
- Dermatology Unit, Ospedale Policlinico San Martino IRCCS, Genoa, Italy
| | - Luigi Molfetta
- University of Genoa, School of Medical and Pharmaceutical Sciences, Research Centre of Ostoeporosis and osteoarticular disease Di.M.I., Policlinic hospital San Martino, Genoa, Italy
| | - Emanuele Cozzani
- Section of Dermatology, Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy.,Dermatology Unit, Ospedale Policlinico San Martino IRCCS, Genoa, Italy
| | - Aurora Parodi
- Section of Dermatology, Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy.,Dermatology Unit, Ospedale Policlinico San Martino IRCCS, Genoa, Italy
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10
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Saternus R, Vogt T, Reichrath J. Update: Solar UV Radiation, Vitamin D, and Skin Cancer Surveillance in Organ Transplant Recipients (OTRs). ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020; 1268:335-353. [PMID: 32918227 DOI: 10.1007/978-3-030-46227-7_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Although great progress has been achieved during the last decades, the clinical management of organ transplant recipients (OTRs) remains a challenge. OTRs need in general lifelong immunosuppressive therapy that is associated with an increased risk to develop skin cancer and with an unfavorable clinical outcome of these malignancies. Skin cancer prevention measures, including regular full-body examinations, are therefore necessary in OTRs to detect and treat suspicious lesions at an early stage. The frequency of aftercare depends on the individual risk factors of the patient. Patients should apply consistent sun protection with sunscreens and clothing, as well as a monthly self-examination. On the other hand, the need of UVR avoidance increases the risk of vitamin D deficiency, which itself is associated with an increased risk for many diseases, including malignancies. OTRs should therefore be monitored for 25(OH)D status and/or should take vitamin D supplements. It has to be emphasized that an interdisciplinary approach, coordinated by the transplant center, that includes regular skin examinations by a dermatologist, is needed to ensure the best care for the OTRs.
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Affiliation(s)
- Roman Saternus
- Center for Clinical and Experimental Photodermatology, Saarland University, Campus Homburg, Homburg, Germany. .,Department of Dermatology, The Saarland University Hospital, Homburg, Germany.
| | - Thomas Vogt
- Center for Clinical and Experimental Photodermatology, Saarland University, Campus Homburg, Homburg, Germany.,Department of Dermatology, The Saarland University Hospital, Homburg, Germany
| | - Jörg Reichrath
- Center for Clinical and Experimental Photodermatology and Department of Dermatology, Saarland University Medical Center, Homburg, Germany
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11
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Sella S, Bonfante L, Fusaro M, Neri F, Plebani M, Zaninotto M, Aghi A, Innico G, Tripepi G, Michielin A, Prandini T, Calò LA, Giannini S. Efficacy of weekly administration of cholecalciferol on parathyroid hormone in stable kidney-transplanted patients with CKD stage 1-3. Clin Chem Lab Med 2020; 59:343-351. [PMID: 32374278 DOI: 10.1515/cclm-2020-0282] [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: 03/08/2020] [Accepted: 04/10/2020] [Indexed: 11/15/2022]
Abstract
Objectives Kidney transplant (KTx) recipients frequently have deficient or insufficient levels of serum vitamin D. Few studies have investigated the effect of cholecalciferol in these patients. We evaluated the efficacy of weekly cholecalciferol administration on parathyroid hormone (PTH) levels in stable KTx patients with chronic kidney disease stage 1-3. Methods In this retrospective cohort study, 48 stable KTx recipients (37 males, 11 females, aged 52 ± 11 years and 26 months post-transplantation) were treated weekly with oral cholecalciferol (7500-8750 IU) for 12 months and compared to 44 untreated age- and gender-matched recipients. Changes in levels of PTH, 25(OH) vitamin D (25[OH]D), serum calcium, phosphate, creatinine and estimated glomerular filtration rate (eGFR) were measured at baseline, 6 and 12 months. Results At baseline, clinical characteristics were similar between treated and untreated patients. Considering the entire cohort, 87 (94.6%) were deficient in vitamin D and 64 (69.6%) had PTH ≥130 pg/mL. Serum calcium, phosphate, creatinine and eGFR did not differ between groups over the follow-up period. However, 25(OH)D levels were significantly higher at both 6 (63.5 vs. 30.3 nmol/L, p < 0.001) and 12 months (69.4 vs. 30 nmol/L, p < 0.001) in treated vs. untreated patients, corresponding with a significant reduction in PTH at both 6 (112 vs. 161 pg/mL) and 12 months (109 vs. 154 pg/mL) in treated vs. untreated patients, respectively (p < 0.001 for both). Conclusions Weekly administration of cholecalciferol can significantly and stably reduce PTH levels, without any adverse effects on serum calcium and renal function.
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Affiliation(s)
- Stefania Sella
- Department of Medicine, Clinica Medica 1, University of Padova, Padova, Italy
| | - Luciana Bonfante
- Department of Medicine, Nephrology, Dialysis and Transplantation Unit, University of Padova, Padova, Italy
| | - Maria Fusaro
- National Research Council, Institute of Clinical Physiology, Pisa, Italy
| | - Flavia Neri
- Department of Surgery, Renal and Pancreas Transplant Unit, University of Padova, Padova, Italy
| | - Mario Plebani
- Department of Medicine, Laboratory Medicine Unit, University of Padova, Padova, Italy
| | - Martina Zaninotto
- Department of Medicine, Laboratory Medicine Unit, University of Padova, Padova, Italy
| | - Andrea Aghi
- Department of Medicine, Clinica Medica 1, University of Padova, Padova, Italy
| | - Georgie Innico
- Department of Medicine, Nephrology, Dialysis and Transplantation Unit, University of Padova, Padova, Italy
| | - Giovanni Tripepi
- Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, CNR, Institute of Biomedicine, Reggio Calabria, Italy
| | - Alberto Michielin
- Department of Medicine, Clinica Medica 1, University of Padova, Padova, Italy
| | - Tancredi Prandini
- Department of Medicine, Clinica Medica 1, University of Padova, Padova, Italy
| | - Lorenzo A Calò
- Department of Medicine, Nephrology, Dialysis and Transplantation Unit, University of Padova, Padova, Italy
| | - Sandro Giannini
- Department of Medicine, Clinica Medica 1, University of Padova, Padova, Italy
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12
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Infante M, Ricordi C, Padilla N, Alvarez A, Linetsky E, Lanzoni G, Mattina A, Bertuzzi F, Fabbri A, Baidal D, Alejandro R. The Role of Vitamin D and Omega-3 PUFAs in Islet Transplantation. Nutrients 2019; 11:2937. [PMID: 31816979 PMCID: PMC6950335 DOI: 10.3390/nu11122937] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2019] [Revised: 11/21/2019] [Accepted: 11/26/2019] [Indexed: 12/15/2022] Open
Abstract
Recurrence of autoimmunity and allograft rejection represent major challenges that impact the success of islet transplantation. Despite the remarkable improvements achieved in immunosuppression strategies after the publication of the Edmonton protocol, long-term data of intra-hepatic islet transplantation show a gradual decline in beta-cell function. Therefore, there is a growing interest in the investigation of novel, safe and effective anti-inflammatory and immunomodulatory strategies able to promote long-term islet graft survival and notable improvements in clinical outcomes of islet transplant recipients. Vitamin D has been shown to exert anti-inflammatory and immunomodulatory effects. Pre-clinical studies investigating the use of vitamin D and its analogs (alone or in combination with immunosuppressive agents and/or other anti-inflammatory agents, such as omega-3 polyunsaturated fatty acids) showed beneficial results in terms of islet graft survival and prevention of recurrence of autoimmunity/allograft rejection in animal models of syngeneic and allogeneic islet transplantation. Moreover, epidemiologic studies demonstrated that vitamin D deficiency is highly prevalent after solid organ transplantation (e.g., heart, liver or kidney transplantation). However, studies that critically assess the prevalence of vitamin D deficiency among islet transplant recipients have yet to be conducted. In addition, prospective studies aimed to address the safety and efficacy of vitamin D supplementation as an adjuvant immunomodulatory strategy in islet transplant recipients are lacking and are therefore awaited in the future.
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Affiliation(s)
- Marco Infante
- Diabetes Research Institute (DRI) and Clinical Cell Transplant Program, Miller School of Medicine, University of Miami, Miami, FL 33136, USA; (C.R.); (N.P.); (A.A.); (G.L.); (D.B.); (R.A.)
- Department of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy;
| | - Camillo Ricordi
- Diabetes Research Institute (DRI) and Clinical Cell Transplant Program, Miller School of Medicine, University of Miami, Miami, FL 33136, USA; (C.R.); (N.P.); (A.A.); (G.L.); (D.B.); (R.A.)
| | - Nathalia Padilla
- Diabetes Research Institute (DRI) and Clinical Cell Transplant Program, Miller School of Medicine, University of Miami, Miami, FL 33136, USA; (C.R.); (N.P.); (A.A.); (G.L.); (D.B.); (R.A.)
| | - Ana Alvarez
- Diabetes Research Institute (DRI) and Clinical Cell Transplant Program, Miller School of Medicine, University of Miami, Miami, FL 33136, USA; (C.R.); (N.P.); (A.A.); (G.L.); (D.B.); (R.A.)
| | - Elina Linetsky
- Diabetes Research Institute (DRI) and Cell Transplant Center, cGMP Cell Processing Facility, Miller School of Medicine, University of Miami, Miami, FL 33136, USA;
| | - Giacomo Lanzoni
- Diabetes Research Institute (DRI) and Clinical Cell Transplant Program, Miller School of Medicine, University of Miami, Miami, FL 33136, USA; (C.R.); (N.P.); (A.A.); (G.L.); (D.B.); (R.A.)
| | - Alessandro Mattina
- Diabetes and Islet Transplantation Unit, Department of Diagnostic and Therapeutic Services, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), UPMC, 90127 Palermo, Italy;
| | | | - Andrea Fabbri
- Department of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy;
| | - David Baidal
- Diabetes Research Institute (DRI) and Clinical Cell Transplant Program, Miller School of Medicine, University of Miami, Miami, FL 33136, USA; (C.R.); (N.P.); (A.A.); (G.L.); (D.B.); (R.A.)
| | - Rodolfo Alejandro
- Diabetes Research Institute (DRI) and Clinical Cell Transplant Program, Miller School of Medicine, University of Miami, Miami, FL 33136, USA; (C.R.); (N.P.); (A.A.); (G.L.); (D.B.); (R.A.)
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13
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Sidhaye A, Goldswieg B, Kaminski B, Blackman SM, Kelly A. Endocrine complications after solid-organ transplant in cystic fibrosis. J Cyst Fibros 2019; 18 Suppl 2:S111-S119. [DOI: 10.1016/j.jcf.2019.08.019] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Revised: 08/18/2019] [Accepted: 08/19/2019] [Indexed: 01/07/2023]
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14
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Passeron T, Bouillon R, Callender V, Cestari T, Diepgen TL, Green AC, van der Pols JC, Bernard BA, Ly F, Bernerd F, Marrot L, Nielsen M, Verschoore M, Jablonski NG, Young AR. Sunscreen photoprotection and vitamin D status. Br J Dermatol 2019; 181:916-931. [PMID: 31069788 PMCID: PMC6899926 DOI: 10.1111/bjd.17992] [Citation(s) in RCA: 108] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/03/2019] [Indexed: 12/16/2022]
Abstract
Background Global concern about vitamin D deficiency has fuelled debates on photoprotection and the importance of solar exposure to meet vitamin D requirements. Objectives To review the published evidence to reach a consensus on the influence of photoprotection by sunscreens on vitamin D status, considering other relevant factors. Methods An international panel of 13 experts in endocrinology, dermatology, photobiology, epidemiology and biological anthropology reviewed the literature prior to a 1‐day meeting in June 2017, during which the evidence was discussed. Methods of assessment and determining factors of vitamin D status, and public health perspectives were examined and consequences of sun exposure and the effects of photoprotection were assessed. Results A serum level of ≥ 50 nmol L−1 25(OH)D is a target for all individuals. Broad‐spectrum sunscreens that prevent erythema are unlikely to compromise vitamin D status in healthy populations. Vitamin D screening should be restricted to those at risk of hypovitaminosis, such as patients with photosensitivity disorders, who require rigorous photoprotection. Screening and supplementation are advised for this group. Conclusions Sunscreen use for daily and recreational photoprotection does not compromise vitamin D synthesis, even when applied under optimal conditions. What's already known about this topic?
Knowledge of the relationship between solar exposure behaviour, sunscreen use and vitamin D is important for public health but there is confusion about optimal vitamin D status and the safest way to achieve this. Practical recommendations on the potential impact of daily and/or recreational sunscreens on vitamin D status are lacking for healthy people. What does this study add?
Judicious use of daily broad‐spectrum sunscreens with high ultraviolet (UV) A protection will not compromise vitamin D status in healthy people. However, photoprotection strategies for patients with photosensitivity disorders that include high sun‐protection factor sunscreens with high UVA protection, along with protective clothing and shade‐seeking behaviour are likely to compromise vitamin D status. Screening for vitamin D status and supplementation are recommended in patients with photosensitivity disorders. Linked Comment: https://doi.org/10.1111/bjd.18126. https://doi.org/10.1111/bjd.18494 available online
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Affiliation(s)
- T Passeron
- Department of Dermatology, CHU Nice, Université Côte d'Azur, CHU Nice, 151, route de Ginestière, 06200, Nice, France.,C3M, INSERM U1065 Université Côte d'Azur, 151, route de Ginestière, 06200, Nice, France
| | - R Bouillon
- Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Gasthuisberg, 3000, Leuven, Belgium
| | - V Callender
- Callender Dermatology & Cosmetic Center, 12200 Annapolis Road, Suite 315, Glenn Dale, MD, 20769, U.S.A
| | - T Cestari
- Federal University of Rio Grande do Sul, Hospital de Clinicas de Porto Alegre, Ramiro Barcellos 2350 zone 13, Porto Alegre, RS, 90035-903, Brazil
| | - T L Diepgen
- Department of Clinical Social Medicine, University of Heidelberg, Voßstr. 2, 69115, Heidelberg, Germany
| | - A C Green
- Cancer and Population Studies Group, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.,CRUK Manchester Institute and Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, M13 9NQ, U.K
| | - J C van der Pols
- School of Exercise and Nutrition Science, Queensland University of Technology, Brisbane, QLD, 4059, Australia
| | - B A Bernard
- L'Oréal R&I, Scientific Directorate, 9 rue Pierre Dreyfus, 92110, Clichy, France
| | - F Ly
- Faculty of Medicine, Pharmacy and Odontology, University Cheikh Anta Diop of Dakar, BP 5825, Dakar, Senegal
| | - F Bernerd
- L'Oréal R&I, 1 Avenue Eugène Schueller, 93600, Aulnay-sous-bois, France
| | - L Marrot
- L'Oréal R&I, 1 Avenue Eugène Schueller, 93600, Aulnay-sous-bois, France
| | - M Nielsen
- L'Oréal R&I, Scientific Directorate, 9 rue Pierre Dreyfus, 92110, Clichy, France
| | - M Verschoore
- L'Oréal R&I, Scientific Directorate, 9 rue Pierre Dreyfus, 92110, Clichy, France
| | - N G Jablonski
- Department of Anthropology, The Pennsylvania State University, 409 Carpenter Building, University Park, PA, 16802, U.S.A
| | - A R Young
- St John's Institute of Dermatology, King's College London, London, SE1 9RT, U.K
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15
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Lynch Cronin I, Byrne F, Doyle R, Fraser WD, Chipchase A, Eustace JA. The Effect of Short-Term Vitamin D Supplementation on Calcium Status in Vitamin D Insufficient Renal Transplant Recipients at Risk of Hypercalcemia. J Ren Nutr 2019; 29:181-187. [DOI: 10.1053/j.jrn.2018.11.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2018] [Revised: 10/08/2018] [Accepted: 11/18/2018] [Indexed: 12/28/2022] Open
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16
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Ferrándiz-Pulido C, Torres IB, Juárez-Dobjanschi C, Zarzoso-Muñoz I, Berastegui C, Castells L, García-Patos V, Moreso F. Vitamin D deficiency in solid-organ transplant recipients from a Spanish Mediterranean population. Clin Exp Dermatol 2019; 44:e103-e109. [PMID: 30701578 DOI: 10.1111/ced.13915] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/10/2018] [Indexed: 01/17/2023]
Abstract
BACKGROUND Solid-organ transplant recipients (SOTRs) are at risk of developing vitamin D deficiency, mainly caused by reduced sunlight exposure with subsequent low vitamin D synthesis in the skin. AIM To analyse whether SOTRs from a Spanish Mediterranean region were vitamin D-deficient. METHODS This was a cross-sectional, descriptive and observational study in a transplantation-specialized Dermatological Unit from a Mediterranean area to determine the calcidiol levels of a cohort of 78 consecutively attending patients not receiving vitamin D supplements. Serum 25(OH)D3 levels were determined and clinical characteristics were collected. Logistic regression analysis was used to analyse variables associated with dichotomized 25(OH)D3 levels (≤ or > 10 ng/mL). RESULTS The cohort comprised 30 lung, 29 kidney and 19 liver transplant recipients. Mean calcidiol was 18 ± 9 ng/mL. Deficiency of 25(OH)D3 was present in 19% of patients, while 68% had insufficient levels and 13% had sufficient levels. Following multivariate logistic regression analysis, the season of blood sampling remained the only predictor of deficient 25(OH)D3 levels. CONCLUSION Despite living in a mid-latitude country with sunny weather, our SOTR population was at high risk of developing hypovitaminosis D, especially in autumn/winter. Avoiding sun exposure is important to prevent skin cancer, but careful monitoring of vitamin D status is recommended, with supplementation if hypovitaminosis D is detected.
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Affiliation(s)
- C Ferrándiz-Pulido
- Department of Dermatology, Hospital Universitari Vall d'Hebron, Barcelona, Spain
| | - I B Torres
- Department of Nephrology, Hospital Universitari Vall d'Hebron, Barcelona, Spain
| | - C Juárez-Dobjanschi
- Department of Dermatology, Hospital Universitari Vall d'Hebron, Barcelona, Spain
| | - I Zarzoso-Muñoz
- Department of Dermatology, Hospital Universitari Vall d'Hebron, Barcelona, Spain
| | - C Berastegui
- Department of Pneumology, Hospital Universitari Vall d'Hebron, Barcelona, Spain
| | - L Castells
- Department of Internal Medicine-Hepatology, Hospital Universitari Vall d'Hebron, Barcelona, Spain
| | - V García-Patos
- Department of Dermatology, Hospital Universitari Vall d'Hebron, Barcelona, Spain
| | - F Moreso
- Department of Nephrology, Hospital Universitari Vall d'Hebron, Barcelona, Spain
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17
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de Gruijl FR, Wolterbeek R, Pavel S, de Fijter JW, Hamdy NAT, Bouwes Bavinck JN. Low wintertime pre-diagnostic vitamin D status is associated with an increased risk of internal malignancies in kidney transplant recipients. Photochem Photobiol Sci 2018; 17:1946-1955. [PMID: 30397693 DOI: 10.1039/c7pp00404d] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Low serum 25-hydroxyvitamin D (25OHD) concentrations have been associated with increased cancer risk, but the relative importance of seasonality, i.e. high summer concentrations versus low winter concentrations, is unclear. We investigated this issue in a high risk group: kidney transplant recipients with known increased risk of cancer and low vitamin D statuses. We examined the relationship between registered concentrations of 25OHD binned by quarter and subsequent risk of internal malignancy or cutaneous squamous cell carcinoma in 1112 kidney transplant recipients. Hazard ratios for internal malignancies were significantly increased with lower pre-diagnostic 25OHD concentrations in the first quarter of the year (January-March); a 1.4 fold increase (95%CI 1.1;1.7) per 10 nmol L-1 decrease in 25OHD. Except for women in April-June (1.3 (1.01;1.7) per 10 nmol L-1 decrease) pre-diagnostic 25OHD concentrations in the other quarters were not statistically significantly associated with internal malignancies. Higher 25OHD concentrations tended to be associated with the development of cutaneous squamous cell carcinomas, independent of the time of the year. Our study indicates that low wintertime 25OHD concentrations are associated with an increased risk of internal malignancies and that transplant recipients may benefit from wintertime vitamin D supplementation. Our findings need further corroboration, but suggest that the lowest concentrations of vitamin D, which occur in winter, are important for the risk of internal malignancies.
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Affiliation(s)
- Frank R de Gruijl
- Dept. of Dermatology, Leiden University Medical Center, Leiden, The Netherlands.
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18
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Nolte Fong JV, Moore LW. Nutrition Trends in Kidney Transplant Recipients: the Importance of Dietary Monitoring and Need for Evidence-Based Recommendations. Front Med (Lausanne) 2018; 5:302. [PMID: 30430111 PMCID: PMC6220714 DOI: 10.3389/fmed.2018.00302] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2018] [Accepted: 10/11/2018] [Indexed: 12/19/2022] Open
Abstract
Many physiological properties of the renal system influence nutrient metabolism, elimination, and homeostasis. Kidney failure poses significant challenges to maintaining adequate nutrition, most of which transplantation ameliorates. Comprehensive recommendations for managing nutritional derangements for patients with chronic kidney disease and end stage renal disease exist; however, there are only sparse guidelines for post-transplant malnutrition and adverse outcomes. Not only are guidelines limited, but little is known about dietary trends of post-kidney transplant recipients. This review describes guidelines for prevalent metabolic and nutritional complications post-kidney transplantation and also evaluates changes in caloric intake and diet composition after transplantation. This topic is important because nutrition influences allograft function and a number of cardiovascular risk factors including blood pressure, dyslipidemia, weight, and diabetes. In addition, many dietary recommendations and modifiable lifestyle changes should be tailored for specific complications of transplant patients, namely immunosuppression side effects, dietary restrictions, and electrolyte imbalances.
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Affiliation(s)
- Joy V Nolte Fong
- Department of Surgery, Houston Methodist Hospital, Houston, TX, United States
| | - Linda W Moore
- Department of Surgery, Houston Methodist Hospital, Houston, TX, United States
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19
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Timalsina S, Sigdel MR, Baniya S, Subedee S. Status of vitamin D and parameters of calcium homeostasis in renal transplant recipients in Nepal: a cross sectional study. BMC Nephrol 2018; 19:290. [PMID: 30348109 PMCID: PMC6198466 DOI: 10.1186/s12882-018-1088-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2018] [Accepted: 10/09/2018] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Vitamin D, apart from being an important part of the "calcium-vitamin D-parathyroid hormone" endocrine axis, has diverse range of "non-calcemic" biological actions. A high prevalence of vitamin D deficiency has been observed in renal transplant recipients (RTRs) worldwide. This study aimed to determine the prevalence of hypovitaminosis D in Nepalese RTRs and interrelations between serum 25-hydroxyvitamin D [25(OH) D] and other biochemical parameters. METHODS A total of 80 adult RTRs visiting a university hospital were enrolled in this cross sectional study. Serum 25(OH) D and intact parathyroid hormone (iPTH) were measured using Enhanced Chemiluminiscent Immunoassay. The RTR population was categorized into recent transplant recipients (≤1 year) and long term recipients (> 1 year). The vitamin D status was defined as per NKF/KDOQI guidelines. SPSS version 20.0 was used to analyze the data. Appropriate statistical tests were applied to compare variables between groups and establish correlation. P < 0.05 was considered to be statistically significant. RESULTS The mean age of the recipients was 38.11 ± 11.47 years (68 males, 85.0%). Chronic glomerulonephritis was the leading cause of CKD. The two RTR groups (recent and long term) didn't differ in demographic and biochemical characteristics. 83.75% of the recipients had PTH levels above the upper limit of the recommended range for their stage of CKD. 57.5% had hypocalcemia and none of the recipients had hypercalcemia. The median serum 25(OH) D was 24.15 ng/ml (8.00-51.50 ng/ml). Only 27.5% had sufficient vitamin D status whereas 53.8% were vitamin D insufficient and 18.8% were vitamin D deficient, the distribution almost comparable in the 2 transplant group. The serum 25(OH) D was not significantly affected by the time post-transplant, gender and sunlight avoidance. There was a significant negative correlation between serum 25(OH) D and iPTH (Pearson's r = - 0.35, P = 0.001), but not so with the graft function. CONCLUSION There is a high prevalence of vitamin D insufficiency in RTRs. The deficiency status is not corrected despite of nutritional improvement and normalization of GFR post-transplantation and likely exacerbates secondary hyperparathyroidism. Vitamin D supplementation coupled with sensible sun exposure could be important strategies in optimization of the vitamin D status in this population.
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Affiliation(s)
- Santosh Timalsina
- Department of Biochemistry, Chitwan Medical College, Bharatpur, Nepal
| | - Mahesh Raj Sigdel
- Department of Nephrology, Tribhuvan University Teaching Hospital, Kathmandu, Nepal
| | - Santosh Baniya
- Department of General Practice and Emergency Medicine, Tribhuvan University Teaching Hospital, Kathmandu, Nepal
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20
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Vitamin D Concentration in Patients After Heart and Kidney Transplantation. Transplant Proc 2018; 50:2100-2104. [PMID: 30177117 DOI: 10.1016/j.transproceed.2018.02.171] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2017] [Accepted: 02/06/2018] [Indexed: 11/23/2022]
Abstract
BACKGROUND One of the main actions of vitamin D is bone mineralization regulation. Vitamin D is linked also to hypertension, diabetes, and cardiovascular disease. Vitamin D deficiency may result in osteomalacia, but its excess may result in bone calcium mobilization. Kidney transplant recipients are also at risk of hypovitaminosis D because of impaired graft function. The aim of the study was to assess vitamin D concentration in patients after heart and kidney transplantation. MATERIAL AND METHODS Ninety-eight stable heart transplant recipients were enrolled in the study; 80 kidney transplant recipients and 22 healthy volunteers served as controls. The laboratory tests, including parameters of 25-hydroxyvitamin D (calcidiol), were assayed using commercially available kits. RESULTS Calcidiol deficiency (level below 10 ng/mL) was observed in 10% of the transplant group and in 55 % of the orthotopic heart transplant recipients (OHT). There was positive correlation between calcidiol concentration, hemoglobin, kidney function, and serum glucose in kidney transplant recipients. In OHT, vitamin D correlated with age, kidney function, hemoglobin, cholesterol, low-density lipoprotein cholesterol, and glucose. Both groups had similar kidney function. In both groups of patients with estimated glomerular filtration rate above 60 mL/min/1.72 m2, vitamin D was significantly higher. In OHT, vitamin D was higher in nondiabetic patients. In OHT in multivariate analysis, vitamin D was predicted in 24% by kidney function (beta = -0.30; P = .02) and hemoglobin concentration (beta = 0.25; P = .03). CONCLUSIONS Vitamin D deficiency is more common in patients after heart transplantation than in kidney allograft recipients despite similar kidney function. The possible associations between the cardiovascular system and vitamin D merit further studies.
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21
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Serum 25-Hydroxyvitamin D Level Is Not Related to Regulatory T Cells or Kidney Function in Renal Transplant Recipients. Transplant Proc 2018; 50:1802-1806. [PMID: 30056904 DOI: 10.1016/j.transproceed.2018.03.117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2017] [Revised: 03/15/2018] [Accepted: 03/23/2018] [Indexed: 10/17/2022]
Abstract
BACKGROUND Vitamin D and regulatory T cells (Tregs) are both involved in promoting peripheral tolerance and limiting chronic inflammatory diseases. Renal transplant recipients (RTRs) are likely to have low vitamin D levels, which may influence their immune status. AIM The aim of our study was to assess the usefulness of serum 25-hydroxyvitamin D (25(OH)D) and Tregs in estimation of the protolerogenic milieu in RTRs within 1 year after kidney transplantation. METHODS 26 RTRs (15M/11F, aged 49.1 ± 15.4 years) 3 to 13 months after kidney transplantation and 24 healthy volunteers were enrolled for the study. The serum level of 25(OH)D was measured with ELISA and peripheral blood immune cell populations (T lymphocytes, helper T lymphocytes, and Tregs) were assessed by flow cytometry. RESULTS Severe 25(OH)D deficiency (<10 ng/mL) was found in one RTR (3%) and moderate deficiency (<20 ng/mL) in 12 (46%), while vitamin D sufficiency was found in 6 patients (23%). The RTRs did not differ from the control group in observed 25(OH)D levels. None of the cell populations were related to the level of 25(OH)D in the control group. In RTRs, there was a negative association between 25(OH)D and total T lymphocyte count (rs = -0.45, P = .023), but 25(OH)D was not related to any other cell population or kidney function. CONCLUSION The results of our study suggest that serum 25(OH)D is not sufficiently reflective of vitamin D status to apply this measure in assessment of protolerogenic milieu in RTRs.
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Vangala C, Pan J, Cotton RT, Ramanathan V. Mineral and Bone Disorders After Kidney Transplantation. Front Med (Lausanne) 2018; 5:211. [PMID: 30109232 PMCID: PMC6079303 DOI: 10.3389/fmed.2018.00211] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2018] [Accepted: 07/09/2018] [Indexed: 12/16/2022] Open
Abstract
The risk of mineral and bone disorders among patients with chronic kidney disease is substantially elevated, owing largely to alterations in calcium, phosphorus, vitamin D, parathyroid hormone, and fibroblast growth factor 23. The interwoven relationship among these minerals and hormones results in maladaptive responses that are differentially affected by the process of kidney transplantation. Interpretation of conventional labs, imaging, and other fracture risk assessment tools are not standardized in the post-transplant setting. Post-transplant bone disease is not uniformly improved and considerable variation exists in monitoring and treatment practices. A spectrum of abnormalities such as hypophosphatemia, hypercalcemia, hyperparathyroidism, osteomalacia, osteopenia, and osteoporosis are commonly encountered in the post-transplant period. Thus, reducing fracture risk and other bone-related complications requires recognition of these abnormalities along with the risk incurred by concomitant immunosuppression use. As kidney transplant recipients continue to age, the drivers of bone disease vary throughout the post-transplant period among persistent hyperparathyroidism, de novo hyperparathyroidism, and osteoporosis. The use of anti-resorptive therapies require understanding of different options and the clinical scenarios that warrant their use. With limited studies underscoring clinical events such as fractures, expert understanding of MBD physiology, and surrogate marker interpretation is needed to determine ideal and individualized therapy.
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Affiliation(s)
- Chandan Vangala
- Division of Nephrology and Solid-Organ Transplantation, Michael E. DeBakey VA Medical Center, Houston, TX, United States
| | - Jenny Pan
- Division of Nephrology and Solid-Organ Transplantation, Michael E. DeBakey VA Medical Center, Houston, TX, United States
| | - Ronald T Cotton
- Division of Abdominal Transplantation, Department of Surgery, Baylor College of Medicine, Houston, TX, United States
| | - Venkat Ramanathan
- Division of Nephrology and Solid-Organ Transplantation, Michael E. DeBakey VA Medical Center, Houston, TX, United States
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Wilimborek J, Nowicki M, Kurnatowska I. Seasonal Variation of Vitamin D Status in Long-Term Kidney Transplant Recipients. Transplant Proc 2018; 49:2086-2091. [PMID: 29149966 DOI: 10.1016/j.transproceed.2017.07.009] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2017] [Accepted: 07/30/2017] [Indexed: 12/16/2022]
Abstract
BACKGROUND There is little information about circannual rhythm of vitamin D level in kidney transplantation (KTx) patients. MATERIAL AND METHODS In 71 patients (27 females; 44 males) in the long term after KTx (5.5 ± 2.6 years) during the winter and summer months plasma concentration of 25-hydroxyvitamin D (25(OH)D), 1,25-hydroxyvitamin D, parathormone (PTH), fibroblast growth factor 23 (FGF-23), calcium, and phosphorus were assessed. Vitamin D status was classified according to 25(OH)D level (ie, insufficiency, ≤30 ng/mL; deficiency, <15 ng/mL). RESULTS In this study, 96% of KTx patients had vitamin D insufficiency including 37% deficiency during winter and 89% of KTx patients had vitamin D insufficiency and 24% had vitamin D deficiency, respectively, during summer. Mean 25(OH)D level during winter was lower than in summer (17.4 ± 7.1 vs 20.2 ± 7.2 ng/mL; P = .02), similar to calcitriol (163.6 ± 37.4 vs 284.5 ± 77.8 pmol/L; P = .001). There were no significant differences in winter and summer levels of calcium, phosphorus, and PTH. The 25(OH)D level was significantly higher in patients with estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m2 compared with those with lower eGFR (21.6 ± 7.5 vs 17.6 ± 6.0; P = .02) only in the summer time. CONCLUSIONS Most of the KTx patients have vitamin D insufficiency during both winter and summer with higher concentration of vitamin D metabolites in summer. Other factors than graft function may have an impact on vitamin D levels in KTx patients.
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Affiliation(s)
- J Wilimborek
- Department of Clinical Pharmacology, Medical University of Lodz, Lodz, Poland; Department of Nephrology, Hypertension and Kidney Transplantation, Medical University of Lodz, Lodz, Poland.
| | - M Nowicki
- Department of Nephrology, Hypertension and Kidney Transplantation, Medical University of Lodz, Lodz, Poland
| | - I Kurnatowska
- Department of Clinical Pharmacology, Medical University of Lodz, Lodz, Poland
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Tiryaki O, Usalan C, Tarakcioglu M, Coban S. Calcitriol Reduces Albuminuria and Urinary Angiotensinogen Level in Renal Transplant Recipients. Transplant Proc 2018; 50:1342-1347. [DOI: 10.1016/j.transproceed.2018.01.055] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Accepted: 01/23/2018] [Indexed: 12/22/2022]
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Abstract
Vitamin D plays a key role in skeletal and cardiovascular disorders, cancers, central nervous system diseases, reproductive diseases, infections, and autoimmune and dermatological disorders. The two main sources of vitamin D are sun exposure and oral intake, including vitamin D supplementation and dietary intake. Multiple factors are linked to vitamin D status, such as Fitzpatrick skin type, sex, body mass index, physical activity, alcohol intake, and vitamin D receptor polymorphisms. Patients with photosensitive disorders tend to avoid sun exposure, and this practice, along with photoprotection, can put this category of patients at risk for vitamin D deficiency. Maintaining a vitamin D serum concentration within normal levels is warranted in atopic dermatitis, psoriasis, vitiligo, polymorphous light eruption, mycosis fungoides, alopecia areata, systemic lupus erythematosus, and melanoma patients. The potential determinants of vitamin D status, as well as the benefits and risks of vitamin D (with a special focus on the skin), will be discussed in this article.
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Underrecognition and Underestimation of Disturbances in Calcium-Phosphate Balance in Kidney Transplant Recipients. Transplant Proc 2018; 50:1790-1793. [PMID: 30056901 DOI: 10.1016/j.transproceed.2018.02.155] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2017] [Accepted: 02/19/2018] [Indexed: 12/13/2022]
Abstract
Disturbances in mineral metabolism, namely chronic kidney disease-metabolic bone disease, became more profound with impairment of renal function. The aim of the study was to assess how often calcium, phosphate, alkaline phosphatase, and parathyroid hormone (PTH) were measured in kidney transplant recipients relative to hemodialyzed patients. In addition, prevalence of hypercalcemia defined as calcium concentration over 10.5 mg/dL was assessed. PATIENTS AND METHODS We studied 200 kidney allograft recipients and 100 hemodialyzed patients. Calcium, phosphate, alkaline phosphatase, 25-hydroxy vitamin D, and PTH were obtained from outpatient charts. RESULTS All the studied parameters were available in 100% of the hemodialyzed patients. In kidney allograft recipients, calcium and phosphate levels were available in 80%, alkaline phosphatase activity was available in 40%, PTH was available in less than 10%, and vitamin D was available in 1%. Hypercalcemia was present in 10% of hemodialyzed patients and in 5% of kidney allograft recipients. Vitamin D analogue was administered to 98% of hemodialyzed patients, whereas vitamin D was administered to 28% of kidney allograft recipients, particularly those with impaired kidney function. In conclusion, calcium and phosphate are seldom assessed on an outpatient basis in kidney allograft recipients, making the diagnosis and treatment of secondary hyperparathyroidism in this population difficult. Care of kidney transplant recipients could be substantially improved, particularly in regard to chronic kidney disease-metabolic bone disease, when regular check-ups for calcium-phosphate balance are implemented and proper treatment could be introduced to prevent further chronic kidney disease-metabolic bone disease.
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Giannini S, Mazzaferro S, Minisola S, De Nicola L, Rossini M, Cozzolino M. Raising awareness on the therapeutic role of cholecalciferol in CKD: a multidisciplinary-based opinion. Endocrine 2018; 59:242-259. [PMID: 28726185 PMCID: PMC5846860 DOI: 10.1007/s12020-017-1369-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2017] [Accepted: 06/27/2017] [Indexed: 12/19/2022]
Abstract
Vitamin D is recognized to play an essential role in health and disease. In kidney disease, vitamin D analogs have gained recognition for their involvement and potential therapeutic importance. Nephrologists are aware of the use of oral native vitamin D supplementation, however, uncertainty still exists with regard to the use of this treatment option in chronic kidney disease as well as clinical settings related to chronic kidney disease, where vitamin D supplementation may be an appropriate therapeutic choice. Two consecutive meetings were held in Florence in July and November 2016 comprising six experts in kidney disease (N = 3) and bone mineral metabolism (N = 3) to discuss a range of unresolved issues related to the use of cholecalciferol in chronic kidney disease. The panel focused on the following six key areas where issues relating to the use of oral vitamin D remain controversial: (1) vitamin D and parathyroid hormone levels in the general population, (2) cholecalciferol in chronic kidney disease, (3) vitamin D in cardiovascular disease, (4) vitamin D and renal bone disease, (5) vitamin D in rheumatological diseases affecting the kidney, (6) vitamin D and kidney transplantation.
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Affiliation(s)
- Sandro Giannini
- Department of Medicine, Clinica Medica 1, University of Padova, Padova, Italy
| | - Sandro Mazzaferro
- Department of Cardiovascular Respiratory Nephrologic Anesthetic and Geriatric Sciences, Sapienza University of Rome, Rome, Italy
| | - Salvatore Minisola
- Department of Internal Medicine and Medical Disciplines, Sapienza University of Rome, Rome, Italy
| | - Luca De Nicola
- Division of Nephrology, Second University of Naples, Naples, Italy
| | - Maurizio Rossini
- Department of Medicine, Rheumatology Unit, University of Verona, Verona, Italy
| | - Mario Cozzolino
- Department of Health Sciences, Renal Division and Laboratory of Experimental Nephrology, San Paolo Hospital, University of Milan, Milan, Italy.
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Sarno G, Nappi R, Altieri B, Tirabassi G, Muscogiuri E, Salvio G, Paschou SA, Ferrara A, Russo E, Vicedomini D, Vincenzo C, Vryonidou A, Della Casa S, Balercia G, Orio F, De Rosa P. Current evidence on vitamin D deficiency and kidney transplant: What's new? Rev Endocr Metab Disord 2017; 18:323-334. [PMID: 28281103 DOI: 10.1007/s11154-017-9418-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Kidney transplant is the treatment of choice for end-stage chronic kidney disease. Kidneys generate 1,25-dihydroxyvitamin D (calcitriol) from 25-hydroxyvitamin D (calcidiol) for circulation in the blood to regulate calcium levels. Transplant patients with low calcidiol levels have an increased risk of metabolic and endocrine problems, cardiovascular disease, type 2 diabetes mellitus, poor graft survival, bone disorders, cancer, and mortality rate. The recommended calcidiol level after transplant is at least 30 ng/mL (75 nmol/L), which could require 1000-3000 IU/d vitamin D3 to achieve. Vitamin D3 supplementation studies have found improved endothelial function and acute rejection episodes. However, since kidney function may still be impaired, raising calcidiol levels may not lead to normal calcitriol levels. Thus, supplementation with calcitriol or an analog, alfacalcidiol, is often employed. Some beneficial effects found include possible improved bone health and reduced risk of chronic allograft nephropathy and cancer.
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Affiliation(s)
- Gerardo Sarno
- General Surgery and Transplantation Unit - "San Giovanni di Dio e Ruggi D'Aragona" University Hospital, Scuola Medica Salernitana, 84131, Salerno, Italy.
| | - Riccardo Nappi
- General Surgery and Transplantation Unit - "San Giovanni di Dio e Ruggi D'Aragona" University Hospital, Scuola Medica Salernitana, 84131, Salerno, Italy
- Nephrology and Dialisys Unit - "Santa Maria della Misericordia" Hospital, ASUIUD - Udine, Udine, Italy
| | - Barbara Altieri
- Institute of Medical Pathology, Division of Endocrinology and Metabolic Diseases, Catholic University, Rome, Italy
| | - Giacomo Tirabassi
- Division of Endocrinology, Department of Clinical and Molecular Sciences, Umberto I Hospital, Polytechnic University of Marche, Ancona, Italy
| | | | - Gianmaria Salvio
- Division of Endocrinology, Department of Clinical and Molecular Sciences, Umberto I Hospital, Polytechnic University of Marche, Ancona, Italy
| | - Stavroula A Paschou
- Division of Endocrinology and Diabetes, "Aghia Sophia" Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Aristide Ferrara
- General Surgery and Transplantation Unit - "San Giovanni di Dio e Ruggi D'Aragona" University Hospital, Scuola Medica Salernitana, 84131, Salerno, Italy
| | - Enrico Russo
- General Surgery and Transplantation Unit - "San Giovanni di Dio e Ruggi D'Aragona" University Hospital, Scuola Medica Salernitana, 84131, Salerno, Italy
| | - Daniela Vicedomini
- General Surgery and Transplantation Unit - "San Giovanni di Dio e Ruggi D'Aragona" University Hospital, Scuola Medica Salernitana, 84131, Salerno, Italy
| | - Cerbone Vincenzo
- General Surgery and Transplantation Unit - "San Giovanni di Dio e Ruggi D'Aragona" University Hospital, Scuola Medica Salernitana, 84131, Salerno, Italy
| | - Andromachi Vryonidou
- Department of Endocrinology and Diabetes, Hellenic Red Cross Hospital, Athens, Greece
| | - Silvia Della Casa
- Institute of Medical Pathology, Division of Endocrinology and Metabolic Diseases, Catholic University, Rome, Italy
| | - Giancarlo Balercia
- Division of Endocrinology, Department of Clinical and Molecular Sciences, Umberto I Hospital, Polytechnic University of Marche, Ancona, Italy
| | - Francesco Orio
- Endocrinology, Department of Sports Science and Wellness, "Parthenope" University Naples, Naples, Italy
| | - Paride De Rosa
- General Surgery and Transplantation Unit - "San Giovanni di Dio e Ruggi D'Aragona" University Hospital, Scuola Medica Salernitana, 84131, Salerno, Italy
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Messa P, Regalia A, Alfieri CM. Nutritional Vitamin D in Renal Transplant Patients: Speculations and Reality. Nutrients 2017; 9:nu9060550. [PMID: 28554998 PMCID: PMC5490529 DOI: 10.3390/nu9060550] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2017] [Revised: 05/15/2017] [Accepted: 05/22/2017] [Indexed: 12/14/2022] Open
Abstract
Reduced levels of nutritional vitamin D are commonly observed in most chronic kidney disease (CKD) patients and particularly in patients who have received a kidney transplant (KTx). In the complex clinical scenario characterizing the recipients of a renal graft, nutritional vitamin D deficiency has been put in relation not only to the changes of mineral and bone metabolism (MBM) after KTx, but also to most of the medical complications which burden KTx patients. In fact, referring to its alleged pleiotropic (non-MBM related) activities, vitamin D has been claimed to play some role in the occurrence of cardiovascular, metabolic, immunologic, neoplastic and infectious complications commonly observed in KTx recipients. Furthermore, low nutritional vitamin D levels have also been connected with graft dysfunction occurrence and progression. In this review, we will discuss the purported and the demonstrated effects of native vitamin D deficiency/insufficiency in most of the above mentioned fields, dealing separately with the MBM-related and the pleiotropic effects.
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Affiliation(s)
- Piergiorgio Messa
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano 20122, Italy.
- via Festa del Perdono, Università degli Studi di Milano, Milano 20122, Italy.
| | - Anna Regalia
- via Festa del Perdono, Università degli Studi di Milano, Milano 20122, Italy.
| | - Carlo Maria Alfieri
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano 20122, Italy.
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Zimmerman D, House AA, Kim SJ, Booth RA, Zhang T, Ramsay T, Knoll G. The Risk of Acute Rejection Following Kidney Transplant by 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D Status: A Prospective Cohort Study. Can J Kidney Health Dis 2017; 4:2054358117699822. [PMID: 28491335 PMCID: PMC5406125 DOI: 10.1177/2054358117699822] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2016] [Accepted: 01/12/2017] [Indexed: 12/24/2022] Open
Abstract
Background: Prediction of acute kidney transplant rejection remains imperfect despite several known risk factors. There is an increasing appreciation of the potential importance of the vitamin D pathway in immunological disease and transplantation. Objective: The purpose of this study was to determine the association of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D with acute rejection. Design: This was a prospective cohort study. Setting: Three academic adult kidney transplant programs in Ontario, Canada, were chosen. Patients: All consecutive adult patients at the 3 institutions who received a solitary kidney transplant, were able to provide written informed consent, and planned to be followed at the same center post-operatively were included. Measurements: Serum concentration of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were measured at baseline, 3, and 6 months post-transplantation. Acute rejection was classified using Banff criteria. Methods: The co-primary outcome was the association between 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D and time to first occurrence of biopsy-proven acute rejection (BPAR) within the first year after kidney transplantation. Cox proportional hazards models were fitted taking into account the time-varying nature of serum concentrations of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D. Results: From 556 screened patients, data on 327 kidney transplant recipients are included. First BPAR occurred in 54 (16.5%) patients. In adjusted Cox proportional hazards models, the serum concentration of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D was not associated with acute renal transplant rejection (hazard ratio 1.00; 95% [confidence interval] CI, 0.87-1.14, per 10 nmol/L increase, and hazard ratio 0.97; 95% CI, 0.84-1.12, per 10 pmol/L increase, respectively). Limitations: Given the observational design, we cannot rule out the possibility of residual confounding that limited our ability to detect a clinically significant effect of vitamin D metabolites on acute rejection. Conclusions: A low serum concentration of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D is not associated with an increased risk of acute kidney transplant rejection following kidney transplantation.
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Affiliation(s)
- Deborah Zimmerman
- Division of Nephrology, Department of Medicine, Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ontario, Canada
| | - Andrew A House
- Division of Nephrology, Department of Medicine, Schulich School of Medicine & Dentistry, London Health Sciences Centre, Ontario, Canada
| | - S Joseph Kim
- Division of Nephrology, Department of Medicine, University Health Network, Toronto, Ontario, Canada
| | - Ronald A Booth
- Division of Biochemistry, Department of Pathology and Laboratory Medicine, Ottawa Hospital, University of Ottawa, Ontario, Canada
| | - Tinghua Zhang
- Methods Centre, Ottawa Hospital Research Institute, University of Ottawa, Ontario, Canada
| | - Tim Ramsay
- Methods Centre, Ottawa Hospital Research Institute, University of Ottawa, Ontario, Canada
| | - Greg Knoll
- Division of Nephrology, Department of Medicine, Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ontario, Canada
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Protective effect of 1α,25-dihydroxyvitamin D3 on effector CD4+ T cell induced injury in human renal proximal tubular epithelial cells. PLoS One 2017; 12:e0172536. [PMID: 28245293 PMCID: PMC5330482 DOI: 10.1371/journal.pone.0172536] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2016] [Accepted: 02/06/2017] [Indexed: 11/19/2022] Open
Abstract
Background The aim of this study was to investigate the protective effect of 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] on effector CD4+ T cells or on inflammatory cytokine-induced injury in human renal proximal tubular epithelial cells (HRPTEpiC). Methods First, we investigated the effect of 1,25(OH)2D3 on CD4+ T cell proliferation. Second, we examined the effect of 1,25(OH)2D3 on inflammatory cytokine secretion or fibrosis in HRPTEpiC induced by inflammatory cytokines or activated CD4+ T cells using ELISA and real-time PCR. Lastly, we compared urine inflammatory-cytokine (IL-6, IL-8) or KIM-1 levels in kidney transplant recipients low serum 25-hydroxyvitamin D (25(OH)D) group (< 20 ng/mL) (n = 40) and normal 25(OH)D group (n = 50). Results Pre-incubation with 1,25(OH)2D3 significantly reduced the percentages of Th1 and Th17 cells compared to that of Th0 condition (P < 0.05 for each). In contrast, 1,25(OH)2D3 increased the proportion of Th2 and Treg cells in a dose-dependent manner (P < 0.05 for each). Treatment of HRPTEpiC with inflammatory cytokines (TNF-α, IL-17, and TGF-β) or effector CD4+ T cells resulted in increased production of IL-6, IL-8, or KIM-1 from HRPTEpiC in a dose-dependent manner. However, treatment with 1,25(OH)2D3 significantly reduced the level of these cytokines (P < 0.05 for all). Western blot analysis demonstrated that the mTOR/STAT3/ERK pathway was downregulated by 1,25(OH)2D3 in HRPTEpiC. Furthermore, the concentrations of urine IL-6/creatinine (P < 0.05) and Kim-1/creatinine (P < 0.05) were higher in the low 25(OH)D group than in the normal 25(OH)D group in kidney transplant recipients. Conclusion The results of this study suggests that vitamin D may have a significant role in the regulation of inflammation in allograft tissue in kidney transplant recipients. Trial registration All participants provided written informed consent in accordance with the Declaration of Helsinki. This study was approved by the Institutional Review Board of Seoul St. Mary’s Hospital (KC13TNMI0701).
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Ziff OJ, Penny H, Frame S, Cronin A, Goldsmith D. Impact of seasonality on the dynamics of native Vitamin D repletion in long-term renal transplant patients. Clin Kidney J 2017; 10:411-418. [PMID: 28616220 PMCID: PMC5466087 DOI: 10.1093/ckj/sfw136] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2016] [Accepted: 11/14/2016] [Indexed: 01/06/2023] Open
Abstract
Background: Renal transplant recipients (RTRs) are often Vitamin D (VitD) depleted as a result of both chronic kidney disease and mandated sun avoidance behaviours. Repleting VitD may be warranted, but how, and for how long, is unknown, as is the impact of seasonality on the success of repletion. We investigated the impact of seasonality on VitD status following VitD repletion in a large cohort of stable, long-term RTRs. Methods: Serum 25-hydroxyvitamin D [25(OH)D] concentrations and bone biochemistry parameters were analysed from 102 VitD repletion courses in 98 RTRs that had undergone VitD repletion. Repletion was delivered over 6 months with either 240 000 IU colecalciferol if pre-repletion serum VitD was between 20 and 50 nmol/L, or with 360 000 IU if VitD was <20 nmol/L. Twelve months post-repletion 25(OH)D and parathyroid hormone (PTH) were available for 75 patients. Results: At baseline, 25(OH)D was 20.1 ± 1.0 nmol/L, increasing to 65.4 ± 1.8 nmol/L following repletion (+7.55 nmol/L/month, P < 0.0001). Twelve months post-repletion and after no further VitD administration, 25(OH)D fell to 35.4 ± 1.8 nmol/L (14.2 ± 0.7 ng/mL; −2.50 nmol/L/month, P < 0.0001). PTH followed the opposite trend with baseline, repletion-end and post-repletion values being 144.2 ± 12.0, 109.6 ± 7.5 and 129.2 ± 11.4 ng/L, respectively. VitD repletion during the summer was associated with significantly higher at repletion-end 25(OH)D compared with any other time of year [summer 80.9 ± 4.0, autumn 64.1 ± 3.0 (P = 0.002), winter 48.9 ± 3.0 (P <0.001), spring 63.8 ± 2.5 nmol/L (P <0.001)]. There was no hypercalcaemia during repletion and renal transplant function remained stable without any evidence of allograft rejection. Conclusions: VitD repletion can safely and effectively be achieved in the majority of chronic stable RTRs using a 6-month bolus intermediate-dose schedule. Winter repletion is associated with an inadequate response in 25(OH)D; however, all patients experience a post-repletion fall towards deficiency in the absence of maintenance supplementation, irrespective of the season of repletion.
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Affiliation(s)
- Oliver J Ziff
- Department of Nephrology and Transplantation, Guy's and St Thomas' NHS Foundation Trust, London, UK.,Institute of Cardiovascular Sciences, University College London, London, UK
| | - Hugo Penny
- Department of Nephrology and Transplantation, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Sharon Frame
- Department of Nephrology and Transplantation, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Antonia Cronin
- Department of Nephrology and Transplantation, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - David Goldsmith
- Department of Nephrology and Transplantation, Guy's and St Thomas' NHS Foundation Trust, London, UK
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Atis O, Keles M, Cankaya E, Dogan H, Aksoy H, Akcay F. Vitamin D Treatment Effect on Serum Endocan and High-Sensitivity C-Reactive Protein Levels in Renal Transplant Patients. Prog Transplant 2016; 26:335-339. [DOI: 10.1177/1526924816664086] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Context: Endocan is a marker showing endothelial dysfunction and inflammation. Significantly increased endocan levels have been observed in serum of patients with sepsis and cancer. Objective: Our aim was to investigate the relationship between vitamin D treatment and serum endocan and high-sensitivity C-reactive protein (hs-CRP) levels as inflammatory markers in transplant patients. Design: Prospective. Setting: Nephrology clinic. Patients: Thirty-eight renal transplant patients with serum 25-hydroxy-vitamin D (25-OH-vitamin D) levels below 20 ng/mL and transplanted at least 12 months. Intervention: One-time oral dose of 300 000 IU vitamin D3. Main Outcome Measures: Before and after vitamin D treatment, serum endocan, hs-CRP, calcium, phosphorus, and parathyroid hormone (PTH) levels were measured. Results: Median serum endocan and PTH values before vitamin D were significantly higher than those of after treatment values ( P = .001 and P < .001, respectively). On the other hand, serum total calcium and phosphorus levels before vitamin D treatment were lower than the values obtained after vitamin D treatment ( P = .0013 and P < .001, respectively). Serum hs-CRP was lower after vitamin D therapy than before, but the difference was not statistically significant ( P = .06). A moderate negative correlation was determined between endocan and 25-OH-vitamin D levels after treatment with vitamin D ( r = −.36, P = .02). Conclusion: This study has revealed that vitamin D treatment reduced markers of endothelial dysfunction in patients with renal transplantation and vitamin D deficiency.
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Affiliation(s)
- Omer Atis
- Department of Medical Biology, Medical School, Ataturk University, Erzurum, Turkey
| | - Mustafa Keles
- Department of Nephrology, Medical School, Mevlana University, Konya, Turkey
| | - Erdem Cankaya
- Department of Nephrology, Medical School, Ataturk University, Erzurum, Turkey
| | - Hasan Dogan
- Department of Medical Biology, Medical School, Ataturk University, Erzurum, Turkey
| | - Hulya Aksoy
- Department of Medical Biochemistry, Medical School, Ataturk University, Erzurum, Turkey
| | - Fatih Akcay
- Department of Medical Biochemistry, Medical School, Ataturk University, Erzurum, Turkey
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Filipov JJ, Zlatkov BK, Dimitrov EP, Svinarov DA. Higher 25-Hydroxyvitamin D Levels Are Associated With Lower Proteinuria in Kidney Transplant Recipients. EXP CLIN TRANSPLANT 2016; 14:629-633. [PMID: 27483020 DOI: 10.6002/ect.2015.0344] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Proteinuria is associated with decreased graft and patient survival after kidney transplantation. Increasing evidence shows that vitamin D has antiproteinuric and renoprotective effects. The aim of our study was to assess the influence of 25-hydroxyvitamin D levels on proteinuria after kidney transplantation. MATERIAL AND METHODS Between May 1, 2012, and November 30, 2012, we tested 395 kidney transplant recipients for 25-hydroxyvitamin D levels during their regular visits to our transplant center together with routine blood sampling and proteinuria testing. Patients within 12 months of transplant, who had undergone parathyroidectomy, had unstable graft function, had concomitant intake of calcineurin inhibitors and mammalian target of rapamycin inhibitors were not included in the study. Subjects with advanced liver disease, or receiving vitamin D supplementation were also excluded. All laboratory, clinical, and therapeutic factors for proteinuria were taken into consideration. Statistical analyses included descriptive statistics and univariate and multivariate log-log regression with backward selection (SPSS version 22.0; SPSS Inc., Chicago, IL, USA), with significance at P < .05. Determination of total 25-hydroxyvitamin D levels was performed by a validated liquid chromatography-tandem mass spectrometry method. RESULTS Our study group included 230 patients (148 men, 82 women). Positive association was established between proteinuria and history of diabetes mellitus, rejection episode 12 months within testing for 25-hydroxyvitamin D levels, and use of mammalian target of rapamycin inhibitors (P < .05). Significant negative relations were detected for patient age, graft function, and 25-hydroxyvitamin D concentrations (P < .05). CONCLUSIONS Our study established that better vitamin D status is associated with lower proteinuria. However, further research is needed to clarify the possible renoprotective properties of vitamin D.
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Affiliation(s)
- Jean J Filipov
- From the Department of Nephrology and Transplantation, and University Hospital "Alexandrovska," and the Medical University, Sofia, Bulgaria
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Morrone LF, Bolasco P, Camerini C, Cianciolo G, Cupisti A, Galassi A, Mazzaferro S, Russo D, Russo L, Cozzolino M. Vitamin D in patients with chronic kidney disease: a position statement of the Working Group "Trace Elements and Mineral Metabolism" of the Italian Society of Nephrology. J Nephrol 2016; 29:305-328. [PMID: 27062486 DOI: 10.1007/s40620-016-0305-6] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2016] [Accepted: 03/30/2016] [Indexed: 02/07/2023]
Abstract
In the late 1970s, calcitriol was introduced into clinical practice for the management of secondary renal hyperparathyroidism in chronic kidney disease (CKD). Since then, the use of calcifediol or other native forms of vitamin D was largely ignored until the publication of the 2009 Kidney Disease Improving Global Outcomes (KDIGO) recommendations. The guidelines suggested that measurement of circulating levels of 25(OH)D (calcifediol) and its supplementation were to be performed on the same basis as for the general population. This indication was based on the fact that the precursors of active vitamin D had provided to CKD patients considerable benefits in survival, mainly due to their pleiotropic effects on the cardiovascular system. However, despite the long-term use of various classes of vitamin D in CKD, a clear definition is still lacking concerning the most appropriate time for initiation of therapy, the best compound to prescribe (active metabolites or analogs), the proper dosage, and the most suitable duration of therapy. The aim of this position statement is to provide and critically appraise the current plentiful evidence on vitamin D in different clinical settings related to CKD, particularly focusing on outcomes, monitoring and treatment-associated risks. However, it should be taken in account that position statements are meant to provide guidance; therefore, they are not to be considered prescriptive for all patients and, importantly, they cannot replace the judgment of clinicians.
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Affiliation(s)
- Luigi Francesco Morrone
- Nephrology, Dialysis and Renal Transplantation Unit, University Hospital "Policlinico", Bari, Italy.
| | - Pergiorgio Bolasco
- Territorial Unit of Nephrology and Dialysis-ASL 8 of Cagliari, Cagliari, Italy
| | - Corrado Camerini
- Operative Unit of Nephrology, AO Spedali Civili di Brescia and University of Brescia, Brescia, Italy
| | - Giuseppe Cianciolo
- Nephrology Dialysis and Renal Transplantation Unit, S. Orsola University Hospital, Bologna, Italy
| | - Adamasco Cupisti
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | | | - Sandro Mazzaferro
- Department of Cardiovascular Respiratory Nephrologic Anesthetic and Geriatric Sciences, Sapienza University of Rome, Rome, Italy
| | - Domenico Russo
- Department of Public Health, Unit of Nephrology and Hypertension, University of Naples Federico II, Naples, Italy
| | - Luigi Russo
- Department of Public Health, Unit of Nephrology and Hypertension, University of Naples Federico II, Naples, Italy
| | - Mario Cozzolino
- Renal Division and Laboratory of Experimental Nephrology, Department of Health Sciences, San Paolo Hospital, University of Milan, Milan, Italy
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Fibroblast growth factor-23, vitamin D and mineral metabolism in renal transplant recipients. INDIAN JOURNAL OF TRANSPLANTATION 2016. [DOI: 10.1016/j.ijt.2016.03.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
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Taweesedt PT, Disthabanchong S. Mineral and bone disorder after kidney transplantation. World J Transplant 2015; 5:231-242. [PMID: 26722650 PMCID: PMC4689933 DOI: 10.5500/wjt.v5.i4.231] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2015] [Revised: 09/11/2015] [Accepted: 10/27/2015] [Indexed: 02/05/2023] Open
Abstract
After successful kidney transplantation, accumulated waste products and electrolytes are excreted and regulatory hormones return to normal levels. Despite the improvement in mineral metabolites and mineral regulating hormones after kidney transplantation, abnormal bone and mineral metabolism continues to present in most patients. During the first 3 mo, fibroblast growth factor-23 (FGF-23) and parathyroid hormone levels decrease rapidly in association with an increase in 1,25-dihydroxyvitamin D production. Renal phosphate excretion resumes and serum calcium, if elevated before, returns toward normal levels. FGF-23 excess during the first 3-12 mo results in exaggerated renal phosphate loss and hypophosphatemia occurs in some patients. After 1 year, FGF-23 and serum phosphate return to normal levels but persistent hyperparathyroidism remains in some patients. The progression of vascular calcification also attenuates. High dose corticosteroid and persistent hyperparathyroidism are the most important factors influencing abnormal bone and mineral metabolism in long-term kidney transplant (KT) recipients. Bone loss occurs at a highest rate during the first 6-12 mo after transplantation. Measurement of bone mineral density is recommended in patients with estimated glomerular filtration rate > 30 mL/min. The use of active vitamin D with or without bisphosphonate is effective in preventing early post-transplant bone loss. Steroid withdrawal regimen is also beneficial in preservation of bone mass in long-term. Calcimimetic is an alternative therapy to parathyroidectomy in KT recipients with persistent hyperparathyroidism. If parathyroidectomy is required, subtotal to near total parathyroidectomy is recommended. Performing parathyroidectomy during the waiting period prior to transplantation is also preferred in patients with severe hyperparathyroidism associated with hypercalcemia.
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Rapid calcitriol increase and persistent calcidiol insufficiency in the first 6 months after kidney transplantation. Nucl Med Commun 2015; 36:489-93. [PMID: 25603274 DOI: 10.1097/mnm.0000000000000265] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
INTRODUCTION Vitamin D deficiency or insufficiency is prevalent in kidney transplant recipients. Little is known about post-transplantation changes in vitamin D forms, which are essential for bone health and other health outcomes. The aim was to measure the levels of calcidiol and calcitriol during the first 6 months after kidney transplantation and examine their relation with other bone mineral metabolic parameters. PATIENTS AND METHODS A prospective study was performed on 98 patients recruited between April 2010 and June 2011. Calcidiol and calcitriol levels were measured at baseline and at days 15, 30, 90, and 180 after kidney transplantation. RESULTS Serum calcidiol levels remained persistently low: 14.3 (9-22) ng/ml at baseline and 16.3 (10.1-20.6) ng/ml at 6 months (P=0.641). At 6 months, calcidiol levels showed an inverse correlation with simultaneously measured parathyroid hormone levels. Calcidiol showed a trend to be higher in patients transplanted in spring but with no statistically significant difference. Calcitriol levels increased from 17 (13-23.7) pg/ml at baseline to 24 (16-32) pg/ml (P=0.002) in the first 2 weeks after transplantation and reached 37 (25-50) pg/ml (P=0.000) after 6 months. During the follow-up, calcitriol levels showed a significant inverse correlation with baseline fibroblast growth factor-23 levels. At month 6, calcitriol levels were inversely correlated with baseline fibroblast growth factor-23 levels and directly correlated with calcidiol levels. CONCLUSION In most patients, calcidiol levels remain low 6 months after kidney transplantation, whereas calcitriol levels rapidly return to normal. Lower calcidiol blood levels promoted lower calcitriol blood levels and higher parathyroid hormone concentrations.
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Wong J, Tan MZW, Chandran M. Fifty shades of gray: Bone disease in renal transplantation. PROCEEDINGS OF SINGAPORE HEALTHCARE 2015. [DOI: 10.1177/2010105815611808] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Kidney transplantation is the renal replacement therapy of choice for patients with end stage renal disease. Advances in technology, surgical techniques and pharmacotherapy have improved renal allograft survival. Increasingly, we are seeing long term side effects related to renal transplantation, bone disease being a major one amongst them. Renal transplant patients have a higher risk of fragility fractures even when compared to those who remain on dialysis. This is likely to be related to pre-existing underlying bone disease and the emergence of new metabolic bone problems post-transplant. Conditions such as persistent hyperparathyroidism and the use of certain immunosuppressive agents have a deleterious effect on the post renal transplant bone. Remarkable advances in the field of metabolic bone research have been made in the last decade and newer imaging techniques, biomarkers and therapeutic options are now available for osteoporosis in the general population. Interest is being focused on attempting to extrapolate these new discoveries to the management of bone disease post renal transplant. This review will briefly describe the metabolic bone changes that occur after transplantation and will provide an update on the currently available investigative options and therapeutic strategies for the management of post renal transplant bone disease.
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Affiliation(s)
- Jiunn Wong
- Department of Renal Medicine, Singapore General Hospital, Singapore
| | | | - Manju Chandran
- Department of Endocrinology, Singapore General Hospital, Singapore
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Schalka S, Steiner D, Ravelli FN, Steiner T, Terena AC, Marçon CR, Ayres EL, Addor FAS, Miot HA, Ponzio H, Duarte I, Neffá J, Cunha JAJD, Boza JC, Samorano LDP, Corrêa MDP, Maia M, Nasser N, Leite OMRR, Lopes OS, Oliveira PD, Meyer RLB, Cestari T, Reis VMSD, Rego VRPDA. Brazilian consensus on photoprotection. An Bras Dermatol 2015; 89:1-74. [PMID: 25761256 PMCID: PMC4365470 DOI: 10.1590/abd1806-4841.20143971] [Citation(s) in RCA: 65] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2014] [Accepted: 10/28/2014] [Indexed: 12/14/2022] Open
Abstract
Brazil is a country of continental dimensions with a large heterogeneity of climates
and massive mixing of the population. Almost the entire national territory is located
between the Equator and the Tropic of Capricorn, and the Earth axial tilt to the
south certainly makes Brazil one of the countries of the world with greater extent of
land in proximity to the sun. The Brazilian coastline, where most of its population
lives, is more than 8,500 km long. Due to geographic characteristics and cultural
trends, Brazilians are among the peoples with the highest annual exposure to the sun.
Epidemiological data show a continuing increase in the incidence of non-melanoma and
melanoma skin cancers. Photoprotection can be understood as a set of measures aimed
at reducing sun exposure and at preventing the development of acute and chronic
actinic damage. Due to the peculiarities of Brazilian territory and culture, it would
not be advisable to replicate the concepts of photoprotection from other developed
countries, places with completely different climates and populations. Thus the
Brazilian Society of Dermatology has developed the Brazilian Consensus on
Photoprotection, the first official document on photoprotection developed in Brazil
for Brazilians, with recommendations on matters involving photoprotection.
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Affiliation(s)
- Sérgio Schalka
- Photobiology Department, Sociedade Brasileira de Dermatologia, São Paulo, SP, Brazil
| | | | | | | | | | | | - Eloisa Leis Ayres
- Center of Dermatology Prof. Rene Garrido Neves, City Health Foundation, Rio de Janeiro, RJ, Brazil
| | | | | | - Humberto Ponzio
- Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Ida Duarte
- Charity Hospital, Santa Casa de Misericórdia, São Paulo, SP, Brazil
| | - Jane Neffá
- Fluminense Federal University, Niterói, RJ, Brazil
| | | | | | | | | | - Marcus Maia
- Charity Hospital, Santa Casa de Misericórdia, São Paulo, SP, Brazil
| | - Nilton Nasser
- Federal University of Santa Catarina, Blumenau, SC, Brazil
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Filipov JJ, Zlatkov BK, Dimitrov EP, Svinarov D. Relationship between vitamin D status and immunosuppressive therapy in kidney transplant recipients. BIOTECHNOL BIOTEC EQ 2015; 29:331-335. [PMID: 26019648 PMCID: PMC4433925 DOI: 10.1080/13102818.2014.995415] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2014] [Accepted: 10/27/2014] [Indexed: 12/04/2022] Open
Abstract
There is a growing body of evidence for the protective role of vitamin D in diabetes mellitus (DM), infection, cancer, cardiovascular disease, immune disorders and kidney function. Considering the reported high prevalence of vitamin D insufficiency among kidney transplant recipients (KTRs), the aim of this study was to assess the influence of immunosuppressive therapy and other factors on vitamin D status in such patients. The study included 289 KTRs (189 males and 100 females) who consented to participate. The first test for 25-hydrohyvitamin D [25(OH)D] was performed by a validated liquid chromatography-tandem mass spectrometry method. Influence of immunosuppressive drugs and previously reported predictors on vitamin D status was assessed by descriptive statistics, univariate and multivariate regression. Our results showed that only 53 patients (18.34%) of the studied KTRs were vitamin D sufficient. In addition to a well expected positive association between serum 25(OH)D and summer blood sampling (p < 0.05) and inverse relationship between vitamin D status and DM, gender (female) and body mass index, serum 25(OH)D was found to be inversely associated with calcineurin inhibitors (CNI) (p < 0.05) and unaffected by other immunosuppressive agents. Our study demonstrated high prevalence of vitamin D insufficiency after kidney transplantation in the studied cohort of patients. Apart from female gender, winter months, DM and overweight, the use of CNI could be considered an additional significant predictor of lower 25(OH)D in Bulgarian KTRs.
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Affiliation(s)
- Jean Jeanov Filipov
- Department of Nephrology and Transplantation, University Hospital ‘Alexandrovska’, Medical University of Sofia, Sofia, Bulgaria
| | - Borelli Kirilov Zlatkov
- Department of Nephrology and Transplantation, University Hospital ‘Alexandrovska’, Medical University of Sofia, Sofia, Bulgaria
| | - Emil Paskalev Dimitrov
- Department of Nephrology and Transplantation, University Hospital ‘Alexandrovska’, Medical University of Sofia, Sofia, Bulgaria
| | - Dobrin Svinarov
- Laboratory of Therapeutic Drug Management & Clinical Pharmacology, University Hospital ‘Alexandrovska’, Medical University of Sofia, Sofia, Bulgaria
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Baxmann AC, Menon VB, Medina-Pestana JO, Carvalho AB, Heilberg IP. Overweight and body fat are predictors of hypovitaminosis D in renal transplant patients. Clin Kidney J 2014; 8:49-53. [PMID: 25713710 PMCID: PMC4310423 DOI: 10.1093/ckj/sfu120] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2014] [Accepted: 10/17/2014] [Indexed: 12/19/2022] Open
Abstract
Background Hypovitaminosis D has been frequently reported after renal transplantation, but the impact of obesity and other factors in the reduction of vitamin D levels is not well established. We aimed to evaluate risk factors contributing to hypovitaminosis D among nondiabetic renal transplant recipients (RTR) with serum creatinine <2.0 mg/dL, at least 6 months after transplantation. Methods One hundred RTR were subjected to anthropometric evaluation and body composition assessment through bioelectrical impedance analysis; blood samples were drawn for biochemical and hormonal determinations and clinical data were retrieved from the medical records. Results Hypovitaminosis D was observed in 65% and overweight (body mass index, BMI >25 kg/m2) in 59% of cases with a significant median weight gain after transplantation of 5.1 kg. An inadequate distribution of body fat was evidenced in 50% of males and in 58% of females. Patients with either vitamin D deficiency or insufficiency presented significantly higher median values of body fat and weight gain since transplantation, as well as lower lean mass compared with patients with normal vitamin D levels (P < 0.001). Moreover, median values of waist circumference, BMI, serum leptin and parathyroid hormone levels were significantly higher in the group with vitamin D deficiency. A multivariate linear regression analysis then revealed that body fat and leptin levels, but not skin color, gender, age, glucocorticoid use, renal function, microalbuminuria and other confounding factors, were independently associated with low levels of 25 hydroxyvitamin D3 even after adjustments for seasonal variations. Conclusion In conclusion, the present study showed body fat and serum leptin levels to be the only independent risk factors for hypovitaminosis D among RTR.
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Obi Y, Hamano T, Ichimaru N, Tomida K, Matsui I, Fujii N, Okumi M, Kaimori JY, Yazawa K, Kokado Y, Nonomura N, Rakugi H, Takahara S, Isaka Y, Tsubakihara Y. Vitamin D deficiency predicts decline in kidney allograft function: a prospective cohort study. J Clin Endocrinol Metab 2014; 99:527-35. [PMID: 24285688 DOI: 10.1210/jc.2013-2421] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
CONTEXT Vitamin D, often deficient in kidney transplant (KTx) recipients, has potential immunomodulatory effects. OBJECTIVE This study aimed to evaluate whether vitamin D status affects the rate of decline in kidney allograft function. DESIGN, SETTING, AND PATIENTS The study included a prospective cohort of 264 ambulatory KTx recipients at a single Japanese center. MAIN OUTCOME MEASURES We measured the baseline 25-hydroxyvitamin D (25D) concentration and examined its association with annual decline in estimated glomerular filtration rate (eGFR). Secondary outcome was rescue treatment with iv methylprednisolone (IV-MP) as an index of rejection episodes. RESULTS The mean serum 25D concentration was 17.1 (SD 6.5) ng/mL, and 68.4% patients had vitamin D inadequacy or deficiency. Time after KTx was a significant effect modifier for the association of serum 25D concentration with annual eGFR change and need for IV-MP (P for interaction < .1). We divided patients according to the median time after KTx (10 y) and found that low vitamin D was significantly associated with a rapid eGFR decline at less than 10 years after KTx but not at 10 or more years after KTx. The same was true for rescue treatment with IV-MP. Overall, propensity score matching showed independent associations of low vitamin D with both outcomes. Stratified matching confirmed pronounced associations at less than 10 years after KTx. CONCLUSIONS Vitamin D deficiency predicts a rapid decline in eGFR and need for IV-MP at less than 10 years after KTx. Future studies are warranted to evaluate the clinical efficacy of vitamin D supplementation.
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Affiliation(s)
- Yoshitsugu Obi
- Departments of Geriatric Medicine and Nephrology (Y.O., I.M., H.R., Y.I.), Comprehensive Kidney Disease Research (T.H., Y.T.), Advanced Technology for Transplantation (N.I., J.K., S.T.), and Specific Organ Regulation (Urology) (M.O., K.Y., N.N.), Osaka University Graduate School of Medicine, Suita 565-0871, Osaka, Japan; Department of Kidney Disease and Hypertension (K.T.), Osaka General Medical Center, Osaka 558-0056, Osaka, Japan; Department of Internal Medicine (N.F.), Hyogo Prefectural Nishinomiya Hospital, Nishinomiya 662-0918, Hyogo, Japan; and Takahashi Clinic (Y.K.), Toyonaka 570-0027, Osaka, Japan
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Calcidiol deficiency in end-stage organ failure and after solid organ transplantation: status quo. Nutrients 2013; 5:2352-71. [PMID: 23857217 PMCID: PMC3738977 DOI: 10.3390/nu5072352] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2013] [Revised: 06/13/2013] [Accepted: 06/14/2013] [Indexed: 12/13/2022] Open
Abstract
Among patients with organ failure, vitamin D deficiency is extremely common and frequently does not resolve after transplantation. This review crystallizes and summarizes existing data on the status quo of vitamin D deficiency in patients with organ failure and in solid organ transplant recipients. Interventional studies evaluating different treatment strategies, as well as current clinical practice guidelines and recommendations on the management of low vitamin D status in these patients are also discussed.
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Leccia MT. [Skin, sun exposure and vitamin D: facts and controversies]. Ann Dermatol Venereol 2013; 140:176-82. [PMID: 23466150 DOI: 10.1016/j.annder.2012.12.003] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2012] [Revised: 11/16/2012] [Accepted: 12/05/2012] [Indexed: 12/31/2022]
Abstract
Vitamin D plays a clearly defined role in phosphorus, calcium and bone metabolism. In addition to its effects on cellular proliferation and differentiation, and on immunity, it appears to exert other action, poorly understood to date, on human physiology and disease. A number of epidemiological studies have demonstrated a protective role of sun exposure with regard to the incidence of certain immune diseases and cancer, and upon the related mortality rates. Furthermore, over the last 10 years, studies have purported to find levels judged "inadequate" in numerous populations, and, in the absence of any strict scientific arguments, a correlation was established by certain authors between supposedly "inadequate" levels, sun exposure and risk of cancer. However, analysis of the literature shows that there is in fact no precise and consensual definition of normal ranges and that the notion of inadequacy was created artificially using assay techniques lacking in sensitivity and reproducibility. Photosynthesis of vitamin D can in fact be considered perfectly adequate in the majority of populations. However, greater care is needed with elderly subjects and with subjects exposed very little to sunlight. Current studies show that the means of photoprotection used in everyday life do not adversely affect such photosynthesis. In the event of documented vitamin D deficiency, oral supplements should be given, and exposure to natural or artificial UV radiation should not be prescribed. Ultraviolet radiation has been shown to be carcinogenic and responsible for the onset of most skin cancers, and the population must be warned against misleading advertising from the tanning industry. Care should also be taken with regard to the potential harmful effects of inappropriate vitamin D supplementation.
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Affiliation(s)
- M-T Leccia
- Clinique de dermatologie et photobiologie, pôle pluridisciplinaire de médecine, CHU A.-Michallon, 38043 Grenoble cedex, France.
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Mudigonda T, Levender MM, O'Neill JL, West CE, Pearce DJ, Feldman SR. Incidence, risk factors, and preventative management of skin cancers in organ transplant recipients: a review of single- and multicenter retrospective studies from 2006 to 2010. Dermatol Surg 2012. [PMID: 23190408 DOI: 10.1111/dsu.12028] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Organ transplant recipients (OTRs) taking immunosuppressants are at high risk of skin cancer, which is the most common malignant condition in OTRs, so dermatologic surveillance is important for OTRs. OBJECTIVES To characterize the most common skin cancers arising from chronic immunosuppression in OTRs. METHODS A PubMed search for retrospective single- and multicenter studies reporting skin cancer incidence from 2006 to 2010 was undertaken. Data regarding each study's immunosuppressive regimen, affected skin cancer cohort, and associated risk factors were extracted. RESULTS Thirty-six articles that met our inclusion criteria reported incidences of nonmelanoma skin cancer (NMSC), Kaposi's sarcoma, melanoma, and Merkel cell carcinoma. NMSC was the most commonly reported cancer of all skin cancers after transplantation. Common risk factors were sex, age, sunlight exposure, and immunosuppressive agent-related (duration, type). CONCLUSION Sun education programs and frequent screenings in organ transplant clinics have provided the best preventative strategies after transplantation, although the characteristics of the immunosuppressive regimen also play an important role. Thus, the adjuvant strategy of modifying immunosuppression may be effective when confronting severe transplant-associated skin cancer. Although the decision-making process for curbing levels of immunosuppression is difficult, further long-term, randomized controlled studies should assess the effect of using less immunosuppressant medication while preserving graft function.
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Affiliation(s)
- Tejaswi Mudigonda
- Department of Dermatology, Center for Dermatology Research, School of Medicine, Wake Forest University, Winston-Salem, North Carolina, USA
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Penny H, Frame S, Dickinson F, Garrett G, Young AR, Sarkany R, Chitalia N, Hampson G, Goldsmith D. Determinants of vitamin D status in long-term renal transplant patients. Clin Transplant 2012; 26:E617-23. [PMID: 23083399 DOI: 10.1111/ctr.12039] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/24/2012] [Indexed: 12/11/2022]
Abstract
In this study, we explored the determinants of vitamin D status in a large cohort of stable, Long-term renal transplant (RTx) patients. Serum 25(OH)D concentrations, and bone biochemistry parameters, were retrospectively analyzed from 266 RTx patients (>10 yr post-engraftment) presenting to clinic over the course of a year. Forty-five percent of the cohort were vitamin D deficient (<37.5 nM), 38% insufficient (37.5 75-nM), and 17% sufficient (>75 nM). Serum 25(OH)D concentrations were higher in patients presenting in summer (p<0.001) and in more active patients (p<0.05). RTx patients with non-melanoma skin cancer (NMSC) (n=45) had higher 25(OH)D concentrations than patients without NMSC (n=221; p<0.05) despite these patients being older, having worse eGFR, transplanted for longer, and less active physically (p<0.05). Lower 25(OH)D concentrations were associated with higher PTH concentrations (p<0.05) which, in the setting of widespread hypovitaminosis, suggests that secondary hyperparathyroidism was common in this cohort. In conclusion, season and activity status are important determinants of vitamin D status. We report, for the first time, that NMSC is associated with higher 25(OH)D, probably through increased UV radiation exposure. Long-term RTx patients may benefit from oral vitamin D supplementation, but this requires a randomized controlled trial to confirm.
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Affiliation(s)
- Hugo Penny
- Department of Nephrology and Transplantation, Guy's and St Thomas' NHS Foundation Trust, London, UK
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48
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Tomida K, Hamano T, Ichimaru N, Fujii N, Matsui I, Nonomura N, Tsubakihara Y, Rakugi H, Takahara S, Isaka Y. Dialysis vintage and parathyroid hormone level, not fibroblast growth factor-23, determines chronic-phase phosphate wasting after renal transplantation. Bone 2012; 51:729-36. [PMID: 22796419 DOI: 10.1016/j.bone.2012.06.027] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2012] [Revised: 06/07/2012] [Accepted: 06/27/2012] [Indexed: 12/11/2022]
Abstract
PURPOSE Fibroblast growth factor 23 (FGF23), rather than parathyroid hormone (PTH), has been shown to be the major factor behind hypophosphatemia in the early period after renal transplantation. However, it is not clear whether phosphate wasting persists in the chronic phase. Purpose of our study is to elucidate whether FGF23 can also explain phosphate wasting, if any, in the chronic phase. METHODS In this cross-sectional observational study, we enrolled 247 recipients who had received a graft more than 1 year prior to this study. We compared the phosphate metabolism of recipients and predialysis chronic kidney disease (CKD) patients who are matched on age and estimated glomerular filtration rate (eGFR). We also investigated the determinants of tubular reabsorption of phosphate normalized for glomerular filtration rate (TmP/GFR), as an index of renal threshold for phosphate. RESULTS Recipients had a median dialysis vintage of 27.0 months and eGFR 41.2 mL/min/1.73 m(2). Whereas hypophosphatemia (<2.4 mg/dL) was observed in 6.1% of the recipients, 55.2% had TmP/GFR lower than 2.4 mg/dL. Recipients showed significantly lower TmP/GFR in all CKD stages than their predialysis counterparts, indicating that phosphate wasting persists in the chronic phase. Compared to predialysis patients, the recipients in stages 2T and 3T showed lower phosphate and higher intact PTH levels, despite a higher percentage being active vitamin D users. However, in stage 4T, phosphate retention masked relative hypophosphatemia. FGF23 was higher in the recipients across all CKD stages, but adjustment for vitamin D prescription revealed that transplantation had no effect on FGF23. Multiple regression analysis in the recipients showed significant negative associations of intact PTH and dialysis vintage with TmP/GFR. CONCLUSIONS Renal phosphate wasting persists in the chronic-phase renal transplantation recipients even with normophosphatemia. Persistent hyperparathyroidism and longer dialysis vintage, not FGF23, was associated with renal phosphate wasting in the chronic phase. Such an impact on phosphate metabolism of the factors determined in dialysis period could be called as "uremic memory". This novel finding in the chronic phase is in sharp contrast to the previous finding in the early phase that FGF23 levels are determinants of phosphate wasting.
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Affiliation(s)
- Kodo Tomida
- Department of Kidney Disease and Hypertension, Osaka General Medical Center, 3-1-56 Bandai-higashi, Osaka, 558-8558, Japan
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García IM, Altamirano L, Mazzei L, Fornés M, Molina MN, Ferder L, Manucha W. Role of mitochondria in paricalcitol-mediated cytoprotection during obstructive nephropathy. Am J Physiol Renal Physiol 2012; 302:F1595-605. [PMID: 22492946 DOI: 10.1152/ajprenal.00617.2011] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Vitamin D slows the progression of chronic kidney disease. Furthermore, activators of vitamin D receptors (VDR) have suppressant effects on the renin-angiotensin system, as well as anti-inflammatory and antifibrotic actions. This study aimed to evaluate the cytoprotective effects of paricalcitol, a VDR activator, at the mitochondrial level using an obstructive nephropathy model [unilateral ureteral obstruction (UUO)]. Rats subjected to UUO and controls were treated daily with vehicle or paricalcitol. The control group underwent a sham surgery. The treatment was done for 15 days (30 ng/kg). The following were determined: biochemical parameters; fibrosis; apoptosis; mitochondrial morphology; VDR, AT(1) receptor, and NADPH oxidase 4 expression; and NADPH oxidase activity (in total and in mitochondrial fractions from the renal cortex). VDR activation prevented fibrosis (20 ± 5 vs. 60 ± 10%) and the number of TUNEL-positive apoptotic cells (10 ± 3 vs. 25 ± 4) in UUO. Biochemical, histological, and molecular studies suggest mitochondrial injury. Electron microscopy revealed in UUO electronically luminous material in the nucleus. Some mitochondria were increased in size and contained dilated crests and larger than normal spaces in their interiors. These changes were not present with paricalcitol treatment. Additionally, high AT(1)-receptor mRNA and NADPH activity was reverted in mitochondrial fractions from obstructed paricalcitol-treated animals (0.58 ± 0.06 vs. 0.95 ± 0.05 relative densitometry units and 9,000 ± 800 vs. 15,000 ± 1,000 relative fluorescence units·μg protein(-1)·min(-1), respectively). These changes were consistent with an improvement in VDR expression (0.75 ± 0.05 vs. 0.35 ± 0.04 relative densitometry units). These results suggest that paricalcitol confers a protective effect and reveal, as well, a possible AT(1) receptor-dependent protective effect that occurs at the mitochondrial level.
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Affiliation(s)
- Isabel Mercedes García
- Área de Fisiopatología, Departamento de Patología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina
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Beani JC. [Solar protection products: efficacy and risks]. Ann Dermatol Venereol 2012; 139:261-72. [PMID: 22482479 DOI: 10.1016/j.annder.2012.01.022] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2011] [Revised: 12/21/2011] [Accepted: 01/31/2012] [Indexed: 12/31/2022]
Abstract
Solar protection products (SPP) containing chemical filters and/or mineral filters are extensively used today in photoprotection; however, concerns continue to be voiced about their efficacy and about their possible dangers. A rapid review of photoprotection strategies shows that SPP owe their photoprotective effect to the absence of other photoprotection methods having clearly established efficacy in healthy subjects; in addition, they exhibit real protective efficacy against the majority of harmful effects of solar radiation, provided they have been devised in keeping with the specifications clearly set out in the recommendations of the French Medicines Agency (Afssaps). Such efficacy is dependent on their correct usage, recently reiterated by Afssaps in its recommendations to end-users concerning the good use of solar products: application of adequate quantities of such products, selection of the appropriate photoprotection class based on phototype and conditions of exposure, and regular renewal of applications in the event of prolonged exposure and after bathing or profuse sweating. Solar filters have long been known to cause contact allergic dermatitis, irritative dermatitis and photosensitisation, and a particular risk has appeared with the use of octocrylene. However, debate has centred primarily on the risk of endocrine disturbance potentially induced by chemical filters, certain of which exhibit established transcutaneous penetration. The risk of mimicry of an effect of oestradiol has been raised on the basis of a series of studies, almost all of which were carried out by the same team, and which mainly concerned 4-methylbenzylidene-camphor (4-MBC) following oral absorption in the rat. The risk of this type of effect with SPPs under normal conditions of use seems fairly remote according to the current state of knowledge; in any event, within the context of the "National Fertility Action Plan", Afssaps has been formally requested to analyse the risk associated with cosmetic substances that are "reprotoxic" and/or affect endocrine function, as a result of which various filters are currently being reassessed for such risk. The greater alleged safety of mineral filters, based on the absence of introduction of risk of photosensitisation (as a result of which they are preferred for use in young children), no longer seems so clear since the introduction of titanium dioxide (TiO2) and zinc oxide (ZnO) in the form of nanoparticles. Afssaps drew up a risk assessment report concerning cutaneous penetration, genotoxicity and oncogenesis for TiO(2) and ZnO in nanoparticle form; further studies are needed before any general conclusions may be drawn. The European Scientific Committee on Consumer Safety (SCCS) is also carrying out an evaluation of the use of TiO(2) and of ZnO as UV filters. Finally, current data do not suggest that SPPs exert any harmful effects by inhibiting the beneficial effects of the sun, in particular, vitamin D synthesis.
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Affiliation(s)
- J-C Beani
- Clinique universitaire de dermato-vénéréologie, allergologie et photobiologie, pôle pluridisciplinaire de médecine, CHU, Grenoble cedex, France.
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