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Mazzaferro S, Tartaglione L, Cohen-Solal M, Hoang Tran M, Pasquali M, Rotondi S, Ureña Torres P. Pathophysiology and therapies of CKD-associated secondary hyperparathyroidism. Clin Kidney J 2025; 18:i15-i26. [PMID: 40083954 PMCID: PMC11903092 DOI: 10.1093/ckj/sfae423] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Indexed: 03/16/2025] Open
Abstract
Uremic secondary hyperparathyroidism (SHP) refers to the biochemical abnormalities that characterize CKD-MBD. However, historically parathyroid hormone (PTH) is identified as the key culprit hormone and the essential biomarker of secondary hyperparathyroidism. SHP represents the adaptive response to several mineral abnormalities that initiate and maintain increased PTH secretion through classical mineral derangements and more recently elucidated hormonal dysregulations. Among classic factors involved in the pathogenesis of SHP, phosphate, calcium, and calcitriol have a prominent role. The discovery of new pathogenetic factors involved in the development of SHP (and the eventual CKD-MBD) including fibroblast growth factor-23 (FGF23) and klotho provides new hypothesis and perspectives to our understanding of this complex metabolic disturbance. Recently more than serum phosphate a critical role in regulating FGF23 synthesis and the progression of CKD is ascribed to phosphate pool, reflected by production of glycerol-3-phosphate and the formation of excessive CPP-2. Finally, also skeletal resistance to PTH action, due to dysregulation of the Wnt-β-catenin system and intestinal dysbiosis, affecting the PTH actions on bone are causal factor of SHP. Identifying all the actors at play is mandatory to allow the most precise therapeutic prescription in the individual patient. This paper aims to review, in particular, the pathophysiology of SHP, which is essential to envisage the eventual therapeutic options for the associated MBD.
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Affiliation(s)
- Sandro Mazzaferro
- Department of Translation and Precision Medicine, Sapienza University of Rome, Rome, Italy
- Nephrology Unit, Department of Internal Medicine and Medical Specialties, Policlinico Umberto I Hospital, Rome, Italy
| | - Lida Tartaglione
- UOSD Dialysis, Department of Internal Medicine and Medical Specialties, Policlinico Umberto I Hospital, Rome, Italy
| | - Martine Cohen-Solal
- Department of Rheumatology, National Reference Center for Rare Bone Disease in Adults, Lariboisière Hospital, APHP. Nord, France
- Inserm U1132, BIOSCAR, Paris, Université Paris Cité, Paris, France
| | - Minh Hoang Tran
- NTT Hi-Tech Institute, Nguyen Tat Thanh University, Ho Chi Minh City, Vietnam
| | - Marzia Pasquali
- Nephrology Unit, Department of Internal Medicine and Medical Specialties, Policlinico Umberto I Hospital, Rome, Italy
| | - Silverio Rotondi
- Department of Translation and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Pablo Ureña Torres
- Department of Nephrology and Dialysis, AURA Saint Ouen-sur-Seine, Paris, France
- Department of Renal Physiology, Necker Hospital, University of Paris Descartes, Paris, France
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Wang Y, Hu C, Li Y, Liu Q, Gao L, Zhang D, Cao L. Association between serum vitamin D and the risk of diabetic kidney disease in patients with type 2 diabetes. Front Med (Lausanne) 2024; 11:1445487. [PMID: 39185464 PMCID: PMC11342449 DOI: 10.3389/fmed.2024.1445487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Accepted: 07/24/2024] [Indexed: 08/27/2024] Open
Abstract
Aims This investigation explored the potential correlation between serum vitamin D concentration and diabetic kidney disease (DKD) among patients with type 2 diabetes mellitus (T2DM). Methods This cross-sectional study assessed 4,570 patients with T2DM drawn from the National Health and Nutrition Examination Survey (NHANES) dataset. Restricted cubic splines were utilized to examine the dose-response relationship between serum vitamin D levels and the risk of DKD in patients with T2DM. Serum vitamin D concentrations were divided into quartiles for multivariable logistic regression analysis to evaluate the association between varying serum vitamin D levels and DKD risk in patients with T2DM. Additionally, sex-stratified analyses were conducted to determine consistency of the results. The influence of vitamin D concentrations on mortality risk was assessed using a Cox regression model. Results Of the patients with T2DM, 33% were diagnosed with DKD. Restricted cubic spline plots revealed a U-shaped relationship between vitamin D levels and DKD risk, with a protective effect noted in the mid-range, indicating optimal serum vitamin D concentrations between 59.6 nmol/L and 84.3 nmol/L. The multivariate Cox regression analysis suggested that higher VID levels were associated with a reduced mortality risk, particularly in male patients. Conclusion The regulation and monitoring of serum vitamin D levels within an optimal range may play a pivotal role in the prevention of DKD in patients with T2DM. Public health strategies should emphasize the regular monitoring of vitamin D levels, especially among populations at elevated risk, to mitigate the progression of DKD and decrease the associated mortality rates.
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Affiliation(s)
- Yujie Wang
- Department of Nephrology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
- Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan, China
| | - Chenggang Hu
- Emergency Department, The Affiliated TCM Hospital of Southwest Medical University, Luzhou, Sichuan, China
| | - Ying Li
- Department of Nephrology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
- Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan, China
| | - Qi Liu
- Department of Nephrology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
- Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan, China
| | - Lichao Gao
- Department of Nephrology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
- Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan, China
| | - Dongmei Zhang
- Department of Nephrology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
- Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan, China
| | - Ling Cao
- Department of Nephrology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
- Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan, China
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Li L, Zhao J. Association of serum 25-hydroxyvitamin D with cardiovascular and all-cause mortality in patients with chronic kidney disease: NHANES 2007‒2018 results. Clinics (Sao Paulo) 2024; 79:100437. [PMID: 38996723 PMCID: PMC11296000 DOI: 10.1016/j.clinsp.2024.100437] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Revised: 06/09/2024] [Accepted: 06/14/2024] [Indexed: 07/14/2024] Open
Abstract
BACKGROUND Vitamin D insufficiency is a prevalent issue in patients suffering from CKD. The purpose of this study was to determine whether serum 25(OH)D levels are associated with all-cause and cardiovascular mortality in patients with CKD. METHODS To examine the associations between 25(OH)D levels and cardiovascular mortality, this retrospective cohort study used the National Health and Nutrition Examination Survey (NHANES) and the National Death Index (NDI) 2007‒2018 database. A total of 2,668 eligible subjects were included in this study, with follow-up conducted until December 31, 2019. The associations were assessed using Cox proportional hazards regression, restricted cubic splines, Kaplan-Meier survival curves, and competing risks survival analysis. Furthermore, subgroup and sensitivity analyses were performed. RESULTS During a median follow-up of 72 months in a weighted population of 11,715,452 eligible participants, there were 665 deaths from any cause, including 196 cardiovascular-related deaths. After adjusting for covariates, lower levels of 25(OH)D were significantly associated with increased risks for both all-cause mortality (HR= 0.85, 95 % CI 0.77∼0.94) and cardiovascular mortality (SHR= 0.80, 95 % CI 0.67∼0.94). Consistent results were also observed when analyzing 25(OH)D as a categorical variable (quartile). Compared to group Q1, both group Q3 (HR = 0.71, 95 % CI 0.54‒0.93) and group Q4 (HR = 0.72, 95 % CI 0.55‒0.94) exhibited a significantly reduced mortality risk. Weighted restricted cubic splines revealed an inverse J-shaped linear association between levels of 25(OH) D and all-cause mortality ((PNonliner > 0.05). Subgroup analysis and sensitivity analysis yielded similar findings. CONCLUSIONS All-cause mortality and cardiovascular disease-related mortality were significantly increased by lower 25(OH)D levels, both as continuous and categorical variables. 25(OH)D has an inverse J-shaped linear association with all-cause and cardiovascular mortality.
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Affiliation(s)
- Luohua Li
- Department of Nephrology, Jiujiang City Key Laboratory of Cell Therapy, Jiujiang No. 1 People's Hospital, Jiujiang, China
| | - Jinhan Zhao
- The Third Unit, The Department of Hepatology. Beijing Youan Hospital, Capital Medical University, Beijing, China; Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China.
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Vervloet MG, Hsu S, de Boer IH. Vitamin D supplementation in people with chronic kidney disease. Kidney Int 2023; 104:698-706. [PMID: 37541585 DOI: 10.1016/j.kint.2023.07.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2023] [Revised: 07/08/2023] [Accepted: 07/13/2023] [Indexed: 08/06/2023]
Abstract
Vitamin D supplements have long been advocated for people with chronic kidney disease based on data from observational studies among the general population and people with chronic kidney disease. These data consistently suggested that higher circulating concentrations of 25-hydroxyvitamin D are associated with improved fracture, cardiovascular, cancer, and mortality outcomes. In the past few years, large clinical trials have been conducted to assess the effects of vitamin D supplements on a range of clinically relevant outcomes. Most of these studies were performed in the general population, but they also enrolled people with chronic kidney disease. Virtually all of these trials were negative and contradicted the observational data. In this review, the key observational data and clinical trials are summarized, and potential explanations for the discrepancies between these studies are discussed.
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Affiliation(s)
- Marc G Vervloet
- Department of Nephrology, Amsterdam University Medical Center, Amsterdam, the Netherlands; Division of Diabetes and Metabolism, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Center (UMC), Amsterdam, the Netherlands.
| | - Simon Hsu
- Kidney Research Institute and Division of Nephrology, University of Washington, Seattle, Washington, USA
| | - Ian H de Boer
- Kidney Research Institute and Division of Nephrology, University of Washington, Seattle, Washington, USA
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Kong SY, Jung E, Hwang SS, Ro YS, Shin SD, Cha KC, Hwang SO. Circulating Vitamin D Level and Risk of Sudden Cardiac Death and Cardiovascular Mortality: A Dose-Response Meta-Analysis of Prospective Studies. J Korean Med Sci 2023; 38:e260. [PMID: 37605499 PMCID: PMC10442497 DOI: 10.3346/jkms.2023.38.e260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Accepted: 04/13/2023] [Indexed: 08/23/2023] Open
Abstract
BACKGROUND We conducted a comprehensive meta-analysis of prospective cohort studies to analyze the effect of circulating vitamin D level on the risk of sudden cardiac death (SCD) and cardiovascular disease (CVD) mortality. METHODS Prospective cohort studies evaluating the association between circulating vitamin D and risk of SCD and CVD mortality were systematically searched in the PubMed and Embase. Extracted data were analyzed using a random effects model and results were expressed in terms of hazard ratio (HR) and 95% confidence interval (CI). Restricted cubic spline analysis was used to estimate the dose-response relationships. RESULTS Of the 1,321 records identified using the search strategy, a total of 19 cohort studies were included in the final meta-analysis. The pooled estimate of HR (95% CI) for low vs. high circulating vitamin D level was 1.75 (1.49-2.06) with I² value of 30.4%. In subgroup analysis, strong effects of circulating vitamin D were observed in healthy general population (pooled HR, 1.84; 95% CI, 1.43-2.38) and the clinical endpoint of SCD (pooled HRs, 2.68; 95% CI, 1.48-4.83). The dose-response analysis at the reference level of < 50 nmol/L showed a significant negative association between circulating vitamin D and risk of SCD and CVD mortality. CONCLUSION Our meta-analysis of prospective cohort studies showed that lower circulating vitamin D level significantly increased the risk of SCD and CVD mortality.
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Affiliation(s)
- So Yeon Kong
- Laboratory of Emergency Medical Services, Seoul National University Hospital Biomedical Research Institute, Seoul, Korea
| | - Eujene Jung
- Laboratory of Emergency Medical Services, Seoul National University Hospital Biomedical Research Institute, Seoul, Korea
- Department of Emergency Medicine, Chonnam National University Hospital, Gwangju, Korea.
| | - Seung-Sik Hwang
- Department of Public Health Sciences, Seoul National University Graduate School of Public Health, Seoul, Korea
| | - Young Sun Ro
- Laboratory of Emergency Medical Services, Seoul National University Hospital Biomedical Research Institute, Seoul, Korea
| | - Sang Do Shin
- Laboratory of Emergency Medical Services, Seoul National University Hospital Biomedical Research Institute, Seoul, Korea
| | - Kyoung-Chul Cha
- Department of Emergency Medicine, Yonsei University Wonju College of Medicine, Kangwon, Korea
| | - Sung Oh Hwang
- Department of Emergency Medicine, Yonsei University Wonju College of Medicine, Kangwon, Korea
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Hsu S, Zelnick LR, Bansal N, Brown J, Denburg M, Feldman HI, Ginsberg C, Hoofnagle AN, Isakova T, Leonard MB, Lidgard B, Robinson‐Cohen C, Wolf M, Xie D, Kestenbaum BR, de Boer IH. Vitamin D Metabolites and Risk of Cardiovascular Disease in Chronic Kidney Disease: The CRIC Study. J Am Heart Assoc 2023; 12:e028561. [PMID: 37421259 PMCID: PMC10382125 DOI: 10.1161/jaha.122.028561] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2022] [Accepted: 04/18/2023] [Indexed: 07/10/2023]
Abstract
Background The ratio of 24,25-dihydroxyvitamin D3/25-hydroxyvitamin D3 (vitamin D metabolite ratio [VDMR]) may reflect functional vitamin D activity. We examined associations of the VDMR, 25-hydroxyvitamin D (25[OH]D), and 1,25-dihydroxyvitamin D (1,25[OH]2D) with cardiovascular disease (CVD) in patients with chronic kidney disease. Methods and Results This study included longitudinal and cross-sectional analyses of 1786 participants from the CRIC (Chronic Renal Insufficiency Cohort) Study. Serum 24,25-dihydroxyvitamin D3, 25(OH)D, and 1,25(OH)2D were measured by liquid chromatography-tandem mass spectrometry 1 year after enrollment. The primary outcome was composite CVD (heart failure, myocardial infarction, stroke, and peripheral arterial disease). We used Cox regression with regression-calibrated weights to test associations of the VDMR, 25(OH)D, and 1,25(OH)2D with incident CVD. We examined cross-sectional associations of these metabolites with left ventricular mass index using linear regression. Analytic models adjusted for demographics, comorbidity, medications, estimated glomerular filtration rate, and proteinuria. The cohort was 42% non-Hispanic White race and ethnicity, 42% non-Hispanic Black race and ethnicity, and 12% Hispanic ethnicity. Mean age was 59 years, and 43% were women. Among 1066 participants without prevalent CVD, there were 298 composite first CVD events over a mean follow-up of 8.6 years. Lower VDMR and 1,25(OH)2D were associated with incident CVD before, but not after, adjustment for estimated glomerular filtration rate and proteinuria (hazard ratio, 1.11 per 1 SD lower VDMR [95% CI, 0.95-1.31]). Only 25(OH)D was associated with left ventricular mass index after full covariate adjustment (0.6 g/m2.7 per 10 ng/mL lower [95% CI, 0.0-1.3]). Conclusions Despite modest associations of 25(OH)D with left ventricular mass index, 25(OH)D, the VDMR, and 1,25(OH)2D were not associated with incident CVD in chronic kidney disease.
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Affiliation(s)
- Simon Hsu
- Division of Nephrology and Kidney Research Institute, Department of MedicineUniversity of WashingtonSeattleWA
| | - Leila R. Zelnick
- Division of Nephrology and Kidney Research Institute, Department of MedicineUniversity of WashingtonSeattleWA
| | - Nisha Bansal
- Division of Nephrology and Kidney Research Institute, Department of MedicineUniversity of WashingtonSeattleWA
| | - Julia Brown
- Division of Nephrology and Hypertension, Department of MedicineLoyola University of ChicagoMaywoodIL
| | - Michelle Denburg
- Division of Pediatric NephrologyDepartment of Pediatrics, The Children’s Hospital of PhiladelphiaPhiladelphiaPA
- Department of Biostatistics, Epidemiology, and InformaticsPerelman School of Medicine at the University of PennsylvaniaPhiladelphiaPA
| | - Harold I. Feldman
- Department of Biostatistics, Epidemiology, and InformaticsPerelman School of Medicine at the University of PennsylvaniaPhiladelphiaPA
- Center for Clinical Epidemiology and BiostatisticsPerelman School of Medicine at the University of PennsylvaniaPhiladelphiaPA
| | - Charles Ginsberg
- Division of Nephrology‐HypertensionUniversity of California, San DiegoSan DiegoCA
| | | | - Tamara Isakova
- Division of Nephrology and Hypertension, Center for Translational Metabolism and Health, Institute for Public Health and MedicineNorthwestern University Feinberg School of MedicineChicagoIL
| | - Mary B. Leonard
- Division of Nephrology, Lucile Packard Children’s HospitalStanford University School of MedicinePalo AltoCA
| | - Benjamin Lidgard
- Division of Nephrology and Kidney Research Institute, Department of MedicineUniversity of WashingtonSeattleWA
| | | | - Myles Wolf
- Division of Nephrology, Department of Medicine, Duke Clinical Research InstituteDuke University School of MedicineDurhamNCUSA
| | - Dawei Xie
- Department of Biostatistics, Epidemiology, and InformaticsPerelman School of Medicine at the University of PennsylvaniaPhiladelphiaPA
- Center for Clinical Epidemiology and BiostatisticsPerelman School of Medicine at the University of PennsylvaniaPhiladelphiaPA
| | - Bryan R. Kestenbaum
- Division of Nephrology and Kidney Research Institute, Department of MedicineUniversity of WashingtonSeattleWA
| | - Ian H. de Boer
- Division of Nephrology and Kidney Research Institute, Department of MedicineUniversity of WashingtonSeattleWA
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Li R, Li Y, Fan Z, Liu Z, Lin J, He M. L-shaped association of serum 25-hydroxyvitamin D with all-cause and cardiovascular mortality in older people with chronic kidney disease: results from the NHANES database prospective cohort study. BMC Public Health 2023; 23:1260. [PMID: 37380964 DOI: 10.1186/s12889-023-16165-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Accepted: 06/21/2023] [Indexed: 06/30/2023] Open
Abstract
BACKGROUND This study was conducted to assess the association of serum 25-hydroxyvitamin D [25(OH)D] concentrations with all-cause and cardiovascular disease (CVD) mortality in older people with chronic kidney disease (CKD) in the United States. METHODS We identified 3230 CKD participants aged ≥ 60 years from the National Health and Nutrition Examination Survey (2001-2018). CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2. Mortality outcomes were determined by linkage to National Death Index (NDI) records through December 31, 2019. Restricted cubic spline based on Cox regression models were utilized to elucidate the nonlinear relationship between serum 25(OH)D concentrations and mortality in patients with CKD. RESULTS During median 74 months of follow-up, 1615 all-cause death and 580 CVD death were recorded. We found an L-shaped association between serum 25(OH)D concentrations and all-cause and CVD mortality, reaching a plateau at 90 nmol/L. Accordingly, per one-unit increment in natural log-transformed 25(OH)D was associated with a 32% and 33% reduced risk of all-cause mortality (hazard ratio [HR] 0.68; 95%CI, 0.56 to 0.83) and CV mortality (HR 0.69; 95%CI, 0.49 to 0.97) in participants with serum 25(OH)D < 90 nmol/L, but no considerable difference was observed in participants with serum 25(OH)D ≥ 90 nmol/L. Compared with those in the deficiency group (< 50 nmol/L), insufficient (50 to < 75 nmol/L) and sufficient group (≥ 75 nmol/L) were significantly associated with lower all-cause mortality (HR,0.83; 95%CI, 0.71 to 0.97 and HR, 0.75; 95%CI, 0.64 to 0.89) and CV mortality (HR,0.87; 95%CI, 0.68 to 1.10 and HR, 0.77; 95%CI, 0.59 to < 1.0), respectively. CONCLUSION An L-shaped relationship between serum 25(OH)D levels with all-cause and CVD mortality was observed in elderly CKD patients in the United States. A 25(OH)D concentration of 90 nmol/L may be the target to reduce the risk of premature death.
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Affiliation(s)
- Rugang Li
- Department of Nephrology, Affiliated Yuebei People's Hospital of Shantou University Medical College, No. 133 South Huimin Road, Shaoguan, 512026, Guangdong, China
| | - Yang Li
- Department of Nephrology, Haikou Municipal People's Hospital and Central South University Xiangya Medical College Affiliated Hospital, Haikou, China
| | - Zhongcheng Fan
- Department of Osteology, Haikou Municipal People's Hospital and Central South University Xiangya Medical College Affiliated Hospital, Haikou, China
| | - Zhaoqi Liu
- Guangdong Medical University, Zhanjiang, 524001, Guangdong, China
| | - Juhua Lin
- Guangdong Medical University, Zhanjiang, 524001, Guangdong, China
| | - Min He
- Department of Nephrology, Affiliated Yuebei People's Hospital of Shantou University Medical College, No. 133 South Huimin Road, Shaoguan, 512026, Guangdong, China.
- Guangdong Medical University, Zhanjiang, 524001, Guangdong, China.
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Grant WB, Al Anouti F, Boucher BJ, Fakhoury HMA, Moukayed M, Pilz S, Al-Daghri NM. Evidence That Increasing Serum 25(OH)D Concentrations to 30 ng/mL in the Kingdom of Saudi Arabia and the United Arab Emirates Could Greatly Improve Health Outcomes. Biomedicines 2023; 11:994. [PMID: 37189612 PMCID: PMC10136066 DOI: 10.3390/biomedicines11040994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 03/17/2023] [Accepted: 03/21/2023] [Indexed: 03/30/2023] Open
Abstract
Accumulating evidence supports the potential protective effects of vitamin D against chronic diseases such as Alzheimer's disease, autoimmune diseases, cancers, cardiovascular disease (ischaemic heart disease and stroke), type 2 diabetes, hypertension, chronic kidney disease, stroke, and infectious diseases such as acute respiratory tract diseases, COVID-19, influenza, and pneumonia, as well as adverse pregnancy outcomes. The respective evidence is based on ecological and observational studies, randomized controlled trials, mechanistic studies, and Mendelian randomization studies. However, randomized controlled trials on vitamin D supplementation have largely failed to show benefits, probably due to poor design and analysis. In this work, we aim to use the best available evidence on the potential beneficial effects of vitamin D to estimate the expected reduction in incidence and mortality rates of vitamin D-related diseases in the Kingdom of Saudi Arabia and the United Arab Emirates if minimum serum 25(OH)D concentrations were to be raised to 30 ng/mL. Estimated reductions by 25% for myocardial infarction incidence, 35% for stroke incidence, 20 to 35% for cardiovascular disease mortality, and 35% for cancer mortality rates depicted a promising potential for raising serum 25(OH)D. Methods to increase serum 25(OH)D concentrations at the population level could include food fortification with vitamin D3, vitamin D supplementation, improved dietary vitamin D intake, and sensible sun exposure.
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Affiliation(s)
- William B. Grant
- Sunlight, Nutrition, and Health Research Center, P.O. Box 641603, San Francisco, CA 94164-1603, USA
| | - Fatme Al Anouti
- Department of Health Sciences, College of Natural and Health Sciences, Zayed University, Abu Dhabi P.O. Box 144534, United Arab Emirates
| | - Barbara J. Boucher
- The Blizard Institute, Barts & The London School of Medicine & Dentistry, Queen Mary University of London, London E12AT, UK
| | - Hana M. A. Fakhoury
- Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia
| | - Meis Moukayed
- School of Arts and Sciences, American University in Dubai, Dubai P.O. Box 28282, United Arab Emirates
| | - Stefan Pilz
- Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria
| | - Nasser M. Al-Daghri
- Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
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Farooqui N, Subbiah A, Chaturvedi P, Sati H, Singh G, Bhowmik D, Agarwal SK, Bagchi S. Association of vitamin D status with disease severity and outcome in Indian patients with IgA nephropathy. BMC Nephrol 2023; 24:15. [PMID: 36650464 PMCID: PMC9843909 DOI: 10.1186/s12882-023-03061-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Accepted: 01/11/2023] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND Vitamin D deficiency has been examined as a risk factor for severity and progression of kidney disease due to its immunomodulatory effects. There is paucity of data about its impact in IgA nephropathy (IgAN). METHODS In a retrospective cohort study, 25 (OH) vitamin D assay was performed in bio-banked baseline serum samples collected during kidney biopsy of 105 adult patients with primary IgAN diagnosed between 2015 and 2019. A level of < 10 ng/mL was defined as Vitamin D deficiency. RESULTS Mean age of patients was 34 ± 10.6 years, 69.5% were males. Mean baseline 25(OH) Vitamin D levels was 15.9 ± 11.9 ng/mL and 41(39%) patients had vitamin D deficiency. Serum albumin level was lower in vitamin D deficient patients compared to those who had higher vitamin D levels (3.7 ± 0.9 vs 4.1 ± 0.7 g/dl, p = 0.018)but there was no significant difference in baseline proteinuria and eGFR. Crescentic lesions were more frequent in vitamin D deficient group (19.5% vs 6.3%, p = 0.022). At median follow up of 21.5 months (6 - 56 months), there was no difference in remission (68.3% vs 65.6%, p = 0.777) and disease progression (12.5% vs 9.4%, p = 0.614) in those with and without Vitamin D deficiency respectively. On multivariate cox proportional hazard analysis, vitamin D deficiency was not a significant risk factor for renal survival (HR-1.79, 95% confidence interval:0.50-6.34, p = 0.368). CONCLUSION There was no association between vitamin D deficiency and disease profile as well as renal outcome in Indian patients with IgAN.
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Affiliation(s)
- Naba Farooqui
- grid.413618.90000 0004 1767 6103All India Institute of Medical Sciences, New Delhi, India
| | - Arunkumar Subbiah
- grid.413618.90000 0004 1767 6103Department of Nephrology, All India Institute of Medical Sciences, New Delhi, India
| | - Pradeep Chaturvedi
- grid.413618.90000 0004 1767 6103Department of Reproductive Biology, All India Institute of Medical Sciences, New Delhi, India
| | - Hem Sati
- grid.413618.90000 0004 1767 6103Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India
| | - Geetika Singh
- grid.413618.90000 0004 1767 6103Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Dipankar Bhowmik
- grid.413618.90000 0004 1767 6103Department of Nephrology, All India Institute of Medical Sciences, New Delhi, India
| | - Sanjay K. Agarwal
- grid.413618.90000 0004 1767 6103Department of Nephrology, All India Institute of Medical Sciences, New Delhi, India
| | - Soumita Bagchi
- grid.413618.90000 0004 1767 6103Department of Nephrology, All India Institute of Medical Sciences, New Delhi, India
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Miller M, Quimby J, Langston C, Ames M, Parker VJ. Effect of calcifediol supplementation on renin-angiotensin-aldosterone system mediators in dogs with chronic kidney disease. J Vet Intern Med 2022; 36:1693-1699. [PMID: 35962709 PMCID: PMC9511075 DOI: 10.1111/jvim.16499] [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: 02/10/2022] [Accepted: 07/12/2022] [Indexed: 11/29/2022] Open
Abstract
Background Chronic kidney disease (CKD) leads to low serum concentrations of vitamin D metabolites. Thus, hypovitaminosis D associated with CKD might contribute to disease progression via increased concentration of renin angiotensin aldosterone system (RAAS) mediators. Objectives To evaluate whether supplementation with calcifediol affects equilibrium concentrations of selected mediators of the RAAS. We hypothesized that vitamin D supplementation will decrease concentration of circulating RAAS mediators in dogs with CKD. Animals Six client‐owned adult dogs with IRIS Stage 2 and 3 CKD. Methods Prospective study. Serum 25‐hydroxyvitamin D (25[OH]D), 1,25‐dihydroxyvitamin D (1,25[OH]2D), 24,25‐dihydroxyvitamin D (24,25[OH]2D), RAAS mediators (angiotensin I/II/III/IV/1‐5/1‐7, and aldosterone), and surrogate angiotensin converting enzyme (ACE) activity (calculated by the ratio of angiotensin II to angiotensin I) were evaluated at baseline, after 3 months of calcifediol supplementation, and 2 months after discontinuing administration of supplement. Results All serum vitamin D metabolite concentrations increased significantly by month 3 (P < .001): 25(OH)D (median 250 ng/mL; range, 204‐310), compared to baseline (median 43.2 ng/mL; range, 33.8‐58.3 ng/mL); 1,25(OH)2D (median 66.1 pg/mL; range, 57.3‐88.1 pg/mL) compared to baseline (median 35.2 pg/mL; range, 29.3‐56.7 pg/mL); 24,25(OH)2D (median 68.4 ng/mL; range, 22.1‐142.0 ng/mL) compared to baseline (median 14.4 ng/mL; range, 9.0‐21.3 ng/mL). Calculated ACE activity was significantly lower at month 3 (median 0.5; range, 0.4‐1.0) compared to baseline (median 0.7; range, 0.6‐1.3; P = .01). There were no significant differences in any of the evaluated RAAS variables at any other time‐point. Conclusions and Clinical Importance Short‐term calcifediol supplementation in this small group of CKD dogs appeared to decrease ACE activity.
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Affiliation(s)
| | - Jessica Quimby
- Department of Veterinary Clinical Sciences, The Ohio State University College of Veterinary Medicine, Columbus, OH
| | - Catherine Langston
- Department of Veterinary Clinical Sciences, The Ohio State University College of Veterinary Medicine, Columbus, OH
| | - Marisa Ames
- Department of Medicine & Epidemiology, University of California Davis, Davis, CA
| | - Valerie J Parker
- Department of Veterinary Clinical Sciences, The Ohio State University College of Veterinary Medicine, Columbus, OH
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Kadry ARM, Lin YS, Caffrey JL, Sonawane B. Vitamin D status in relation to inflammatory risk and albuminuria associated with polycyclic aromatic hydrocarbon exposure in the US population. ARCHIVES OF ENVIRONMENTAL & OCCUPATIONAL HEALTH 2022; 78:88-97. [PMID: 35766980 DOI: 10.1080/19338244.2022.2090890] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with both systematic inflammation and renal dysfunction. Reports have suggested that anti-inflammatory properties of vitamin D may provide protection against renal injury. This cross-sectional study tested the hypothesis that serum 25-hydroxyvitamin D [25(OH)D] moderates the inflammation and albuminuria associated with PAH exposure. Data were obtained from 5,982 subjects aged 20-79 years in the National Health and Nutrition Examination Survey (2001-2010). PAH exposure was estimated by urinary PAH metabolites. Inflammation was defined as serum C-reactive protein (CRP) > 3 mg/L and albuminuria as urinary albumin-to-creatinine ratio > 30 mg/g. The results found that greater PAH exposure was linked with inflammation and albuminuria. Individuals with PAH exposure also tended to have lower 25(OH)D and lower vitamin D was associated with both elevated CRP (Odds ratio [OR] = 1.28, 95% confidence interval [CI] = 1.07-1.54) and urinary albumin (1.35, 95%CI = 1.03-1.77) for any given PAH exposure. Those with lower serum 25(OH)D-to-urinary PAH ratios were likewise at a greater risk of elevated CRP and albuminuria. The findings support prior suggestions that exposure to PAHs is associated with inflammation and albuminuria but suggests further that the risk is higher when vitamin D is lower. Thus, nutritional status becomes an important variable in PAH risk assessment.
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Affiliation(s)
- Abdel-Razak M Kadry
- Office of Research and Development, U.S. Environmental Protection Agency, Washington, District of Columbia, USA
| | - Yu-Sheng Lin
- Office of Research and Development, U.S. Environmental Protection Agency, Washington, District of Columbia, USA
| | - James L Caffrey
- School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, Texas, USA
| | - Babasaheb Sonawane
- Toxicology and Risk Assessment Consulting Services, North Potomac, Maryland, USA
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12
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Etemadi J, Samadifar M, Ghojazadeh M, Motavalli R, Oriyo R, Majidi T, Tayebi Khosroshahi H. The Effects of Cholecalciferol Supplementation on FGF23 and α-Klotho in Hemodialysis Patients With Hypovitaminosis D: A Randomized, Double-Blind, Placebo-Controlled Trial. J Ren Nutr 2022; 32:334-340. [PMID: 34294550 DOI: 10.1053/j.jrn.2021.05.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Revised: 02/24/2021] [Accepted: 05/25/2021] [Indexed: 11/11/2022] Open
Abstract
OBJECTIVE Vitamin D-fibroblast growth factor-23 (FGF-23)-klotho forms an axis that takes part at least in cardiovascular complications in patients with chronic kidney disease. This study aimed to assess the effects of cholecalciferol supplementation on FGF23 and α-klotho in patients with hypovitaminosis D requiring hemodialysis. METHODS In a single-center, parallel-arm, randomized, double-blind, placebo-controlled trial, 86 patients with hypovitaminosis D requiring hemodialysis were enrolled. The patients were randomized into 2 groups (n = 43 each) to receive either 50,000 IU of cholecalciferol or placebo every week for 12 weeks. Accordingly, the serum levels of FGF23 and klotho were measured by ELISA and compared between both groups. RESULTS Serum 25OH(D) levels increased in participants who received cholecalciferol supplementation compared with participants who received placebo (P = .006). In addition, serum FGF23 decreased and α-klotho levels increased in the supplemented group compared with placebo. However, the before-after differences between cholecalciferol supplement and placebo were significant only for α-klotho (P = .035). These effects were not accompanied by changes in the levels of phosphate, total and ionized calcium, and intact parathyroid hormone. CONCLUSION Cholecalciferol supplementation of 50,000 IU for 12 weeks increases α-klotho levels in the serum of kidney failure patients undergoing hemodialysis. This may suggest that patients receiving maintenance hemodialysis can benefit from using cholecalciferol supplementation and increase in serum α-klotho levels.
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Affiliation(s)
- Jalal Etemadi
- Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Maryam Samadifar
- Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Morteza Ghojazadeh
- Research Center for Evidence based-medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Roza Motavalli
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Roghaiyeh Oriyo
- Imam Reza Teaching Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Taraneh Majidi
- Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Kantas T, Avendaño Capriles CA, Babor S, Tamdin T, Al-Rihani H, Thalla A, Adel Abdelmawla A, Mohammed Saeed Muthanna F, Tousif S. Relationship Between Chronic Kidney Disease Staging and Vitamin D Deficiency: A Retrospective Study. Cureus 2022; 14:e21221. [PMID: 35186523 PMCID: PMC8843767 DOI: 10.7759/cureus.21221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/10/2022] [Indexed: 11/05/2022] Open
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14
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Zhou T, Shen L, Li Z, Jia J, Xing H, Wang N, Jiao Q, Fan Y. Severe 25-Hydroxyvitamin D Deficiency May Predict Poor Renal Outcomes in Patients With Biopsy-Proven Diabetic Nephropathy. Front Endocrinol (Lausanne) 2022; 13:871571. [PMID: 35600603 PMCID: PMC9114460 DOI: 10.3389/fendo.2022.871571] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Accepted: 03/30/2022] [Indexed: 11/18/2022] Open
Abstract
AIMS This study aims to investigate the role of 25-hydroxyvitamin D (25(OH)D) levels in predicting renal survival in biopsy-proven diabetic nephropathy (DN) with type 2 diabetes mellitus (DM). METHODS In this retrospective study, a total of 161 biopsy-proven DN patients were enrolled and divided into four groups (normal group: 25(OH)D>20ng/ml; mild group: 10<25(OH)D ≤ 20ng/ml; moderate group: 5<25(OH)D ≤ 10 ng/ml; severe group: 25(OH)D ≤ 5 ng/ml). The effect of the 25(OH)D level on renal survival was evaluated by multivariate Cox regression. RESULTS A total of 161 type 2 DM patients with biopsy-proven DN were enrolled in this study. Patients with lower 25(OH)D levels had higher serum creatinine, urinary albumin creatinine ratio (UACR), total cholesterol, and parathyroid hormone levels as well as lower estimated glomerular filtration rate (eGFR), hemoglobin, albumin, and calcium levels and were more prone to diabetic retinopathy (DR). Rather than proteinuria and renal function, glomerular class and interstitial fibrosis and tubular atrophy (IFTA) had a significant correlation with 25(OH)D levels. Multivariate Cox regression indicated that severe deficiency of 25(OH)D levels was associated with adverse renal outcomes. Compared to the level in the normal group, after adjusting for clinicopathological characteristics, a lower 25(OH)D level remained a risk factor for renal outcomes. The HRs were 3.446 (95% CI 0.366-32.406, p=0.279) for the mild group, 8.009 (95% CI 0.791-81.102, p=0.078) for the moderate group, and 14.957(95%CI 1.364-163.995, P=0.027) for the severe group. CONCLUSION Levels of 25(OH)D less than 5 ng/ml were correlated with worse renal function, more pathological injury and poorer renal prognosis in patients with biopsy-proven DN.
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Affiliation(s)
- Ting Zhou
- Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
- General Practice Department, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Li Shen
- Clinical Research Unit, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
| | - Ze Li
- Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
| | - Junjie Jia
- Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
| | - Haifan Xing
- Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
| | - Niansong Wang
- Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
| | - Qiong Jiao
- Department of Pathology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
- *Correspondence: Ying Fan, ; Qiong Jiao,
| | - Ying Fan
- Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
- *Correspondence: Ying Fan, ; Qiong Jiao,
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15
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Uwaezuoke SN. Vitamin D Analogs Can Retard the Onset or Progression of Diabetic Kidney Disease: A Systematic Review. FRONTIERS IN CLINICAL DIABETES AND HEALTHCARE 2021; 2:763844. [PMID: 36994344 PMCID: PMC10012055 DOI: 10.3389/fcdhc.2021.763844] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Accepted: 09/30/2021] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Previous studies have shown that vitamin D analogs (such as paricalcitol) can reduce albuminuria in patients with diabetes mellitus and retard the progression of diabetic kidney disease (DKD). A recent systematic review reported significant improvement of renal function in patients with DKD who received vitamin D or its analogs. Study-driven data about their use in improving DKD outcomes have continued to accumulate over the years. AIM This paper aims to systematically review the contemporary evidence about the effectiveness of vitamin D analogs in retarding the onset or progression of DKD. METHODS With appropriate descriptors, two electronic databases (PubMed and Google Scholar) were searched for articles published between 2015 and 2021 in the English language. Primary studies that fulfilled the inclusion criteria were selected; their titles and abstracts were screened, and duplicates were removed. Relevant data were retrieved from the final selected studies using a preconceived data-extraction form. RESULTS A total of eight studies (three randomized-controlled trials, one prospective study, and four cross-sectional studies) were reviewed. A total of 6,243 participants were investigated in the eight studies and comprised young adults, middle-aged adults, and the elderly with a male-gender predominance. One randomized controlled trial reported that paricalcitol significantly improved renal function in type 1 diabetes patients with renal impairment when combined with renin-angiotensin-aldosterone system (RAAS) blockers. A strong correlation between vitamin D deficiency and DKD risk was noted in the majority of the cross-sectional studies. High doses of cholecalciferol (4,000 or 10,000 IU/day), given early in DKD, significantly reduced disease prevalence. CONCLUSION Paricalcitol may retard the onset or progression of DKD, especially if administered in combination with RAAS blockers. The association of vitamin D deficiency with DKD risk also supports this therapeutic effect. Future systematic reviews are still needed to strengthen the current evidence on therapeutic benefit of vitamin D or its analogs in DKD.
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Affiliation(s)
- Samuel N. Uwaezuoke
- Department of Pediatrics, University of Nigeria Teaching Hospital, Enugu, Nigeria
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16
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Wang Y, Zheng Y, Chen P, Liang S, He P, Shao X, Cai G, Chen X. The weak correlation between serum vitamin levels and chronic kidney disease in hospitalized patients: a cross-sectional study. BMC Nephrol 2021; 22:292. [PMID: 34445968 PMCID: PMC8393712 DOI: 10.1186/s12882-021-02498-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Accepted: 08/11/2021] [Indexed: 12/18/2022] Open
Abstract
Background Chronic kidney disease (CKD) has become a global public health problem. Accumulating evidence suggested that vitamins play important roles in the progression of CKD. Methods A cross-sectional study was conducted to investigate the vitamin status of patients with CKD at stage 1–5. The serum concentrations of 9 vitamins, vitamin A, B1, B2, B6, B9, B12, C, D, and E were measured by electroanalytical method with a Multi-Vitamin Analyzer. Pearson correlation and multiple linear regression between serum level of vitamins were analyzed. Results The median levels of vitamin A, B1, B2, B6, B9, B12, C and E were within the reference ranges or on the borderline. Vitamin D deficiency was found in all patients. Weak correlation was found between vitamin A or vitamin D and estimated glomerular filtration rate (eGFR). The Pearson correlation coefficient were − 0.21766 and 0.19752, respectively. Hypertension, diabetes mellitus, and atherosclerosis were the major comorbidities. Conclusions For the first time, the serum levels of 9 vitamins were measured simultaneously in patients with CKD at different stages. Vitamin D deficiency was found in all patients. Weak correlation between vitamin A or vitamin D and eGFR was found.
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Affiliation(s)
- Yong Wang
- Department of Nephrology, State Key Laboratory of Kidney Diseases, First Medical Center of Chinese People's Liberation Army General Hospital, Chinese People's Liberation Army Institute of Nephrology, National Clinical Research Center for Kidney Diseases, Fuxing Road 28, 100853, Beijing, China
| | - Ying Zheng
- Department of Nephrology, State Key Laboratory of Kidney Diseases, First Medical Center of Chinese People's Liberation Army General Hospital, Chinese People's Liberation Army Institute of Nephrology, National Clinical Research Center for Kidney Diseases, Fuxing Road 28, 100853, Beijing, China
| | - Pu Chen
- Department of Nephrology, State Key Laboratory of Kidney Diseases, First Medical Center of Chinese People's Liberation Army General Hospital, Chinese People's Liberation Army Institute of Nephrology, National Clinical Research Center for Kidney Diseases, Fuxing Road 28, 100853, Beijing, China
| | - Shuang Liang
- Department of Nephrology, State Key Laboratory of Kidney Diseases, First Medical Center of Chinese People's Liberation Army General Hospital, Chinese People's Liberation Army Institute of Nephrology, National Clinical Research Center for Kidney Diseases, Fuxing Road 28, 100853, Beijing, China
| | - Pengfei He
- Department of Nephrology, State Key Laboratory of Kidney Diseases, First Medical Center of Chinese People's Liberation Army General Hospital, Chinese People's Liberation Army Institute of Nephrology, National Clinical Research Center for Kidney Diseases, Fuxing Road 28, 100853, Beijing, China
| | - Xiaolei Shao
- Department of Nephrology, State Key Laboratory of Kidney Diseases, First Medical Center of Chinese People's Liberation Army General Hospital, Chinese People's Liberation Army Institute of Nephrology, National Clinical Research Center for Kidney Diseases, Fuxing Road 28, 100853, Beijing, China
| | - Guangyan Cai
- Department of Nephrology, State Key Laboratory of Kidney Diseases, First Medical Center of Chinese People's Liberation Army General Hospital, Chinese People's Liberation Army Institute of Nephrology, National Clinical Research Center for Kidney Diseases, Fuxing Road 28, 100853, Beijing, China
| | - Xiangmei Chen
- Department of Nephrology, State Key Laboratory of Kidney Diseases, First Medical Center of Chinese People's Liberation Army General Hospital, Chinese People's Liberation Army Institute of Nephrology, National Clinical Research Center for Kidney Diseases, Fuxing Road 28, 100853, Beijing, China.
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17
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Vitamin D protects glomerular mesangial cells from high glucose-induced injury by repressing JAK/STAT signaling. Int Urol Nephrol 2021; 53:1247-1254. [PMID: 33942213 PMCID: PMC8144147 DOI: 10.1007/s11255-020-02728-z] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2020] [Accepted: 12/02/2020] [Indexed: 01/28/2023]
Abstract
Aim High glucose (HG) induces the production of transforming growth factor (TGF)-β and reactive oxygen species, which further activates JAK/STAT signaling and promotes the synthesis of matrix proteins, contributes to the pathophysiological processes of diabetic nephropathy. This study aims to investigate the protection role of vitamin D (VD) in the kidney in high glucose condition. Methods Rat glomerular mesangial cells were cultured in high glucose medium, with or without VD or VD receptor (VDR) siRNAs treatment. The levels of TGF-β and fibronectin were detected by qRT-PCR, immunoblotting and enzyme-linked immunosorbent assay (ELISA). The levels of phosphorylated JAK2, STAT1 and STAT3, and JAK/STAT signaling downstream genes were examined by immunoblotting and qRT-PCR. Results In rat glomerular mesangial cells, VD treatment can repress the tyrosine phosphorylation of JAK2, STAT1 and STAT3. VD inhibited TGF-β and fibronectin expression which was rescued by vitamin d receptor (VDR) siRNA and STATs inhibitor perficitinib. The JAK/STAT signaling downstream protein coding genes including SOCS1, SOCS3 and type IV collagen were repressed by VD. Meanwhile, the expression of non-coding RNAs such as miR-181a, miR-181b, was repressed by VD, and the expression of miR-34a and Let-7b was upregulated by VD.
Conclusion Vitamin D (VD) treatment inhibits the function of HG on fibronectin production through regulating JAK/STAT pathway. These results provide direct evidences that VD protects glomerular mesangial cells from high glucose-induced injury through repressing JAK/STAT signaling, which has the potential for clinical DN treatment. Supplementary Information The online version contains supplementary material available at 10.1007/s11255-020-02728-z.
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Tuey SM, Atilano-Roque A, Charkoftaki G, Thurman JM, Nolin TD, Joy MS. Influence of vitamin D treatment on functional expression of drug disposition pathways in human kidney proximal tubule cells during simulated uremia. Xenobiotica 2021; 51:657-667. [PMID: 33870862 DOI: 10.1080/00498254.2021.1909783] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Effects of cholecalciferol (VitD3) and calcitriol (1,25-VitD3), on the expression and function of major vitamin D metabolizing enzymes (cytochrome P450 [CYP]2R1, CYP24A1) and select drug transport pathways (ABCB1/P-gp, SLCO4C1/OATP4C1) were evaluated in human kidney proximal tubule epithelial cells (hPTECs) under normal and uraemic serum conditions.hPTECs were incubated with 10% normal or uraemic serum for 24 h followed by treatment with 2% ethanol vehicle, or 100 and 240 nM doses of VitD3, or 1,25-VitD3 for 6 days. The effects of treatment on mRNA and protein expression and functional activity of select CYP enzymes and transporters were assessedUnder uraemic serum, treatment with 1,25-VitD3 resulted in increased mRNA but decreased protein expression of CYP2R1. Activity of CYP2R1 was not influenced by serum or VitD analogues. CYP24A1 expression was increased with 1,25-VitD3 under normal as well as uraemic serum, although to a lesser extent. ABCB1/P-gp mRNA expression increased under normal and uraemic serum, with exposure to 1,25-VitD3. SLCO4C1/OATP4C1 exhibited increased mRNA but decreased protein expression, under uraemic serum + 1,25-VitD3. Functional assessments of transport showed no changes regardless of exposure to serum or 1,25-VitD3.Key findings indicate that uraemic serum and VitD treatment led to differential effects on the functional expression of CYPs and transporters in hPTECs.
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Affiliation(s)
- Stacey M Tuey
- Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA
| | - Amandla Atilano-Roque
- Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA
| | - Georgia Charkoftaki
- Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA.,School of Public Health, Yale University, New Haven, CT, USA
| | - Joshua M Thurman
- Division of Nephrology and Hypertension, School of Medicine, University of Colorado, Aurora, CO, USA
| | - Thomas D Nolin
- Department of Pharmacy and Therapeutics, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA
| | - Melanie S Joy
- Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA.,Division of Nephrology and Hypertension, School of Medicine, University of Colorado, Aurora, CO, USA
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Ziemińska M, Sieklucka B, Pawlak K. Vitamin K and D Supplementation and Bone Health in Chronic Kidney Disease-Apart or Together? Nutrients 2021; 13:809. [PMID: 33804453 PMCID: PMC7999920 DOI: 10.3390/nu13030809] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 02/15/2021] [Accepted: 02/24/2021] [Indexed: 12/16/2022] Open
Abstract
Vitamin K (VK) and vitamin D (VD) deficiency/insufficiency is a common feature of chronic kidney disease (CKD), leading to impaired bone quality and a higher risk of fractures. CKD patients, with disturbances in VK and VD metabolism, do not have sufficient levels of these vitamins for maintaining normal bone formation and mineralization. So far, there has been no consensus on what serum VK and VD levels can be considered sufficient in this particular population. Moreover, there are no clear guidelines how supplementation of these vitamins should be carried out in the course of CKD. Based on the existing results of preclinical studies and clinical evidence, this review intends to discuss the effect of VK and VD on bone remodeling in CKD. Although the mechanisms of action and the effects of these vitamins on bone are distinct, we try to find evidence for synergy between them in relation to bone metabolism, to answer the question of whether combined supplementation of VK and VD will be more beneficial for bone health in the CKD population than administering each of these vitamins separately.
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Affiliation(s)
- Marta Ziemińska
- Department of Monitored Pharmacotherapy, Medical University of Bialystok, 15-222 Bialystok, Poland;
| | - Beata Sieklucka
- Department of Pharmacodynamics, Medical University of Bialystok, 15-222 Bialystok, Poland;
| | - Krystyna Pawlak
- Department of Monitored Pharmacotherapy, Medical University of Bialystok, 15-222 Bialystok, Poland;
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20
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Efficacy of single-dose cholecalciferol in the blood pressure of patients with type 2 diabetes, hypertension and hypovitaminoses D. Sci Rep 2020; 10:19611. [PMID: 33184328 PMCID: PMC7665034 DOI: 10.1038/s41598-020-76646-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Accepted: 10/21/2020] [Indexed: 12/29/2022] Open
Abstract
Observational and experimental data reinforce the concept that vitamin D is associated with the pathogenesis of arterial hypertension. We investigated the effect of a single dose of 100,000 IU of cholecalciferol, in office blood pressure (BP), and 24-h ambulatory blood pressure monitoring (ABPM) in patients with type 2 diabetes mellitus (DM), hypertension, and hypovitaminosis D. Forty-three patients were randomized to a placebo or cholecalciferol group. BP was assessed by office measurements and 24-h ABPM, before and after intervention. At week 8, a greater decrease in median ABPM values was observed in cholecalciferol supplementation than in the placebo group for systolic 24-h (− 7.5 vs. − 1; P = 0.02), systolic daytime (− 7 vs. − 1; P = 0.007), systolic nighttime (− 7.0 vs. 3; P = 0.009), diastolic 24-h (− 3.5 vs. − 1; P = 0.037), and daytime DBP (− 5 vs. 0; P = 0.01). Office DBP was also reduced after vitamin D supplementation. A single dose of vitamin D3 improves BP in patients with type 2 diabetes, hypertension, and vitamin D insufficiency, regardless of vitamin D normalization. Vitamin D supplementation could be a valuable tool to treat patients with type 2 DM, hypertension, and hypovitaminosis D. Trial registration: Clinicaltrials.gov NCT 02204527.
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21
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Serum 25-hydroxyvitamin D status was associated with brachial-ankle pulse wave velocity and mortality among peritoneal dialysis patients. Eur J Clin Nutr 2020; 75:754-758. [PMID: 33097828 DOI: 10.1038/s41430-020-00787-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2019] [Revised: 06/17/2020] [Accepted: 10/13/2020] [Indexed: 11/08/2022]
Abstract
BACKGROUND/OBJECTIVES To investigate the correlation between serum 25-hydroxyvitamin D (25(OH)D) and brachial-ankle pulse wave velocity (baPWV) and mortality among peritoneal dialysis (PD) patients. SUBJECTS/METHODS We retrospectively reviewed the data of 269 PD patients in our center from January 1, 2013, to December 31, 2018. Subjects were divided into groups according to serum 25(OH)D level based on a cut-off of 20 ng/ml. The general linear regression model was employed to explore the correlation between 25(OH)D and baPWV. The correlation between 25(OH)D and mortality was examined in Cox proportional hazards models. RESULTS The mean (±SD) concentration of serum 25(OH)D was 17 (±7.2) ng/ml. Using linear regression analysis, and after adjusting for possible confounders, serum 25(OH)D concentration was found to be negatively associated with baPWV(β = -0.35, p < 0.001). Multivariate analysis showed that lower 25(OH)D level was significantly associated with higher total mortality in PD patients(< 20 ng/ml vs. ≥ 20 ng/ml; HR, 2.27; 95% CI, 1.04-4.93; P = 0.04)(as a continuous variable; HR, 0.94; 95% CI, 0.90-0.98; P = 0.01). CONCLUSIONS Serum 25(OH)D concentration was a significant factor associated with baPWV and mortality among patients with PD. Further studies with larger sample sizes will be needed to confirm this correlation.
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Miller MS, Rudinsky AJ, Klamer BG, Chew DJ, Parker VJ. Association between vitamin D metabolites, vitamin D binding protein, and proteinuria in dogs. J Vet Intern Med 2020; 34:2468-2477. [PMID: 33026128 PMCID: PMC7694856 DOI: 10.1111/jvim.15912] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Revised: 09/02/2020] [Accepted: 09/16/2020] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND Proteinuria has been associated with progression of renal disease and increased morbidity and mortality in dogs and people. In people, proteinuria also has been associated with hypovitaminosis D. Little is known about the relationship between vitamin D metabolism and proteinuria in dogs. OBJECTIVES To further elucidate vitamin D status in dogs with protein-losing nephropathy (PLN) and minimal to no azotemia. We hypothesized that vitamin D metabolites would be lower in dogs with PLN compared to healthy dogs. ANIMALS Twenty-three client-owned adult dogs with PLN and 10 healthy control dogs. METHODS Serum 25-hydroxyvitamin D (25[OH]D), 1,25-dihydroxyvitamin D (1,25[OH]2 D), 24,25-dihydroxyvitamin D (24,25[OH]2 D), serum vitamin D binding protein (VDBP), and urine 25(OH)D concentrations were measured. RESULTS Compared to healthy dogs, dogs with PLN had lower concentrations of all vitamin D metabolites (P < .01). Correlations (rho; 95% confidence interval [CI]) in dogs with PLN are reported. Serum 25(OH)D and 24,25(OH)2 D concentrations were positively correlated with albumin (r = 0.47; 0.07-0.74), and 24,25(OH)2 D was negatively correlated with urine protein-to-creatinine ratio (UPC; r = -0.54; -0.78 to -0.16). Urine 25(OH)D-to-creatinine ratio was negatively correlated with serum albumin concentration (r = -0.77; -0.91 to -0.50) and positively correlated with UPC (r = 0.79; 0.53-0.91). Serum VDBP concentration was positively correlated with serum albumin concentration (r = 0.53; 0.05-0.81). CONCLUSIONS AND CLINICAL IMPORTANCE Dogs with PLN have decreased serum concentrations of vitamin D metabolites. Urine 25(OH)D-to-creatinine ratio and UPC are correlated in PLN dogs. Future studies are needed to assess additional management strategies for dogs with PLN.
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Affiliation(s)
- Matthew S Miller
- Department of Veterinary Clinical Sciences, The Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA
| | - Adam J Rudinsky
- Department of Veterinary Clinical Sciences, The Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA
| | - Brett G Klamer
- Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University, Columbus, Ohio, USA
| | - Dennis J Chew
- Department of Veterinary Clinical Sciences, The Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA
| | - Valerie J Parker
- Department of Veterinary Clinical Sciences, The Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA
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Long-term vitamin D deficiency promotes renal fibrosis and functional impairment in middle-aged male mice. Br J Nutr 2020; 125:841-850. [PMID: 32812524 DOI: 10.1017/s0007114520003232] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Renal fibrosis is common especially in the elderly population. Recently, we found that vitamin D deficiency caused prostatic hyperplasia. This study aimed to investigate whether vitamin D deficiency promotes renal fibrosis and functional impairment. All mice except controls were fed with vitamin D-deficient (VDD) diets, beginning from their early life. The absolute and relative kidney weights on postnatal week 20 were decreased in VDD diet-fed male pups but not in female pups. A mild pathological damage was observed in VDD diet-fed male pups but not in females. Further analysis showed that VDD-induced pathological damage was aggravated, accompanied by renal dysfunction in 40-week-old male pups. An obvious collagen deposition was observed in VDD diet-fed 40-week-old male pups. Moreover, renal α-smooth muscle actin (α-SMA), a marker of epithelial-mesenchymal transition (EMT), and Tgf-β mRNA were up-regulated. The in vitro experiment showed that 1,25-dihydroxyvitamin D3 alleviated transforming growth factor-β1 (TGF-β1)-mediated down-regulation of E-cadherin and inhibited TGF-β1-evoked up-regulation of N-cadherin, vimentin and α-SMA in renal epithelial HK-2 cells. Moreover, 1,25-dihydroxyvitamin D3 suppressed TGF-β1-evoked Smad2/3 phosphorylation in HK-2 cells. These results provide experimental evidence that long-term vitamin D deficiency promotes renal fibrosis and functional impairment, at least partially, through aggravating TGF-β/Smad2/3-mediated EMT in middle-aged male mice.
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Noonan ML, Clinkenbeard EL, Ni P, Swallow EA, Tippen SP, Agoro R, Allen MR, White KE. Erythropoietin and a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHDi) lowers FGF23 in a model of chronic kidney disease (CKD). Physiol Rep 2020; 8:e14434. [PMID: 32476270 PMCID: PMC7261757 DOI: 10.14814/phy2.14434] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Revised: 04/10/2020] [Accepted: 04/13/2020] [Indexed: 12/19/2022] Open
Abstract
Iron-deficiency anemia is a potent stimulator of the phosphaturic hormone Fibroblast growth factor-23 (FGF23). Anemia, elevated FGF23, and elevated serum phosphate are significant mortality risk factors for patients with chronic kidney disease (CKD). However, the contribution of anemia to overall circulating FGF23 levels in CKD is not understood. Our goal was to investigate the normalization of iron handling in a CKD model using the erythropoiesis stimulating agents (ESAs) Erythropoietin (EPO) and the hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHDi) FG-4592, on the production of, and outcomes associated with, changes in bioactive, intact FGF23 ("iFGF23"). Our hypothesis was that rescuing the prevailing anemia in a model of CKD would reduce circulating FGF23. Wild-type mice were fed an adenine-containing diet to induce CKD, then injected with EPO or FG-4592. The mice with CKD were anemic, and EPO improved red blood cell indices, whereas FG-4592 increased serum EPO and bone marrow erythroferrone (Erfe), and decreased liver ferritin, bone morphogenic protein-6 (Bmp-6), and hepcidin mRNAs. In the mice with CKD, iFGF23 was markedly elevated in control mice but was attenuated by >70% after delivery of either ESA, with no changes in serum phosphate. ESA treatment also reduced renal fibrosis markers, as well as increased Cyp27b1 and reduced Cyp24a1 mRNA expression. Thus, improvement of iron utilization in a CKD model using EPO and a HIF-PHDi significantly reduced iFGF23, demonstrating that anemia is a primary driver of FGF23, and that management of iron utilization in patients with CKD may translate to modifiable outcomes in mineral metabolism.
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Affiliation(s)
- Megan L. Noonan
- Department of Medical and Molecular GeneticsIndiana University School of MedicineIndianapolisINUSA
| | - Erica L. Clinkenbeard
- Department of Medical and Molecular GeneticsIndiana University School of MedicineIndianapolisINUSA
| | - Pu Ni
- Department of Medical and Molecular GeneticsIndiana University School of MedicineIndianapolisINUSA
| | - Elizabeth A. Swallow
- Department of AnatomyCell Biology, and PhysiologyIndiana University School of MedicineIndianapolisINUSA
| | - Samantha P. Tippen
- Department of Medical and Molecular GeneticsIndiana University School of MedicineIndianapolisINUSA
- Department of AnatomyCell Biology, and PhysiologyIndiana University School of MedicineIndianapolisINUSA
| | - Rafiou Agoro
- Department of Medical and Molecular GeneticsIndiana University School of MedicineIndianapolisINUSA
| | - Matthew R. Allen
- Department of AnatomyCell Biology, and PhysiologyIndiana University School of MedicineIndianapolisINUSA
- Department of MedicineDivision of NephrologyIndiana University School of MedicineIndianapolisINUSA
| | - Kenneth E. White
- Department of Medical and Molecular GeneticsIndiana University School of MedicineIndianapolisINUSA
- Department of MedicineDivision of NephrologyIndiana University School of MedicineIndianapolisINUSA
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Brahmbhatt S, Mikhail M, Islam S, Aloia JF. Vitamin D and Abdominal Aortic Calcification in Older African American Women, the PODA Clinical Trial. Nutrients 2020; 12:E861. [PMID: 32213826 PMCID: PMC7146156 DOI: 10.3390/nu12030861] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 03/17/2020] [Accepted: 03/20/2020] [Indexed: 12/28/2022] Open
Abstract
Abdominal aortic calcification (AAC) detected on lateral vertebral fracture assessment is associated with increased cardiovascular risk. Vitamin D deficiency and toxicity have been linked with vascular calcification. The objective of this study was to determine the effect of high-dose vitamin D on the progression of AAC. The Physical Performance, Osteoporosis and vitamin D in African American Women (PODA) is a randomized, clinical trial examining the effect of vitamin D. There were 14.7% subjects with AAC in the vitamin D group, compared to 12.1% in the placebo group at baseline. The prevalence of extended AAC at baseline was 6.4% in the vitamin D group and 3.5% in the placebo group. The extended calcification scores over time were not different between groups. There was no association between AAC and serum 25(OH)D. However, PTH was associated with an increase in AAC in the placebo group.
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Affiliation(s)
- Saloni Brahmbhatt
- Bone Mineral Research, NYU Winthrop Hospital/NYU Langone Health, Mineola, NY 11501, USA;
| | - Mageda Mikhail
- Department of Endocrinology, NYU Winthrop Hospital/NYU Langone Health, Mineola, NY 11501, USA;
| | - Shahidul Islam
- Biostatistician, NYU Winthrop Research Institute, NYU Long Island School of Medicine, NYU Langone Health, Mineola, NY 11501, USA;
| | - John F. Aloia
- Bone Mineral Research, NYU Winthrop Hospital/NYU Langone Health, Mineola, NY 11501, USA;
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Snyder S, Hollenbeak CS, Kalantar-Zadeh K, Gitlin M, Ashfaq A. Cost-Effectiveness and Estimated Health Benefits of Treating Patients with Vitamin D in Pre-Dialysis. Forum Health Econ Policy 2020; 23:fhep-2019-0020. [PMID: 32134730 DOI: 10.1515/fhep-2019-0020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Background The optimal timing of treatment with vitamin D therapy for patients with chronic kidney disease (CKD), vitamin D insufficiency, and secondary hyperparathyroidism (SHPT) is a pressing question in nephrology with economic and patient outcome implications. Objective The objective of this study was to estimate the cost-effectiveness of earlier vitamin D treatment in CKD patients not on dialysis with vitamin D insufficiency and SHPT. Design A cost-effectiveness analysis based on a Markov model of CKD progression was developed from the Medicare perspective. The model follows a hypothetical cohort of 1000 Stage 3 or 4 CKD patients over a 5-year time horizon. The intervention was vitamin D therapy initiated in CKD stages 3 or 4 through CKD stage 5/end-stage renal disease (ESRD) versus initiation in CKD stage 5/ESRD only. The outcomes of interest were cardiovascular (CV) events averted, fractures averted, time in CKD stage 5/ESRD, mortality, quality-adjusted life years (QALYs), and costs associated with clinical events and CKD stage. Results Vitamin D treatment in CKD stages 3 and 4 was a dominant strategy when compared to waiting to treat until CKD stage 5/ESRD. Total cost savings associated with treatment during CKD stages 3 and 4, compared to waiting until CKD stage 5/ESRD, was estimated to be $19.9 million. The model estimated that early treatment results in 159 averted CV events, 5 averted fractures, 269 fewer patient-years in CKD stage 5, 41 fewer deaths, and 191 additional QALYs. Conclusions Initiating vitamin D therapy in CKD stages 3 or 4 appears to be cost-effective, largely driven by the annual costs of care by CKD stage, CV event costs, and risks of hypercalcemia. Further research demonstrating causal relationships between vitamin D therapy and patient outcomes is needed to inform decision making regarding vitamin D therapy timing.
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Affiliation(s)
- Sophie Snyder
- BluePath Solutions, 10951 W. Pico Blvd. Suite 120 Los Angeles, CA, USA
| | - Christopher S Hollenbeak
- The Pennsylvania State University, Department of Health Policy and Administration, University Park, PA, USA
| | | | - Matthew Gitlin
- BluePath Solutions, 10951 W. Pico Blvd. Suite 120 Los Angeles, CA, USA
| | - Akhtar Ashfaq
- Clinical R & D and Medical Affairs, Renal Division, Opko Pharmaceuticals, Miami, FL, USA
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Solarin AU, Nourse P, Gajjar P. Vitamin D status of children with moderate to severe chronic Kidney Disease at a Tertiary Pediatric Center in Cape Town. SAUDI JOURNAL OF KIDNEY DISEASES AND TRANSPLANTATION 2020; 30:781-794. [PMID: 31464234 DOI: 10.4103/1319-2442.265453] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
The prevalence of suboptimal Vitamin D levels is higher in patients with chronic kidney disease (CKD) than in the general population. Recent findings suggest that progression of CKD is linked to a suboptimal Vitamin D level. A high percentage of CKD patients have severe Vitamin D deficiency. These patients also have a low level of 25-hydroxy-vitamin D [25(OH)D] and consequently, a reduced ability to form active 1,25-dihydroxyvitamin D. Various factors underlie the low level of 25(OH)D, including a sedentary lifestyle, decreased intake of Vitamin D due to CKD-related dietary restrictions, and decreased synthesis of Vitamin D in skin due to uremia. All these factors may be particularly influential in patients with progressively worsening CKD, including those receiving chronic dialysis. The objective of our study is to determine the prevalence of Vitamin D deficiency in children with CKD stages three to five and those receiving chronic dialysis, to ascertain whether there is a relationship between Vitamin D deficiency and the stage of CKD, and to identify any clinical correlates associated with the Vitamin D status. A single-center, retrospective review was conducted of 46 children (younger than 18 years) with CKD stages 3-5D who attended the renal clinic of the Red Cross Children's Hospital between October 2013 and November 2014. In total, 73.9% of the study population had suboptimal Vitamin D levels (43.5% and 30.4% had Vitamin D deficiency and insufficiency, respectively). The prevalence of Vitamin D deficiency was significantly higher in older children (≥10 years of age) than in younger children (P = 0.000) but did not significantly differ between males and females (P = 0.693). In total, 12 of 15 black children (80%), 19 of 26 colored children (73.1%), two of four white children (50%), and one Asian child (100%) had suboptimal Vitamin D levels. Neither white nor Asian child had Vitamin D deficiency. In addition, 90% of patients undergoing chronic dialysis, 80% of whom were receiving peritoneal dialysis, had suboptimal Vitamin D levels. Age, weight, height, and the albumin concentration were significantly associated with the Vitamin D level. There was a positive linear relationship between the Vitamin D level and the serum albumin concentration (Spearman's rho correlation coefficient = 0.397, P = 0.007). In total, 87.5% of patients with nephrotic-range proteinuria had suboptimal Vitamin D levels, and 80% were Vitamin D deficient (P = 0.004). A higher percentage of Vitamin D deficiency/insufficiency cases was documented during the winter (24/34, 70.6%) than during the summer (10/34, 29.4%); however, this difference was not statistically significant (P = 0.685). Sub-optimal Vitamin D is high among children with moderate to severe CKD and significantly higher in those undergoing chronic dialysis. The emerging evidence of the role of Vitamin D in slowing progression of CKD highlights the need for monitoring and correction of Vitamin D levels in predialysis children.
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Affiliation(s)
- Adaobi Uzoamaka Solarin
- Department of Pediatrics, Lagos State University Teaching Hospital, Ikeja Lagos, Lagos, Nigeria
| | - Peter Nourse
- Department of Pediatrics and Child Health, Red Cross Children's Hospital/University of Cape Town, Cape Town, South Africa
| | - Priya Gajjar
- Department of Pediatrics and Child Health, Red Cross Children's Hospital/University of Cape Town, Cape Town, South Africa
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Abstract
The term uraemic cardiomyopathy refers to the cardiac abnormalities that are seen in patients with chronic kidney disease (CKD). Historically, this term was used to describe a severe cardiomyopathy that was associated with end-stage renal disease and characterized by severe functional abnormalities that could be reversed following renal transplantation. In a modern context, uraemic cardiomyopathy describes the clinical phenotype of cardiac disease that accompanies CKD and is perhaps best characterized as diastolic dysfunction seen in conjunction with left ventricular hypertrophy and fibrosis. A multitude of factors may contribute to the pathogenesis of uraemic cardiomyopathy, and current treatments only modestly improve outcomes. In this Review, we focus on evolving concepts regarding the roles of fibroblast growth factor 23 (FGF23), inflammation and systemic oxidant stress and their interactions with more established mechanisms such as pressure and volume overload resulting from hypertension and anaemia, respectively, activation of the renin-angiotensin and sympathetic nervous systems, activation of the transforming growth factor-β (TGFβ) pathway, abnormal mineral metabolism and increased levels of endogenous cardiotonic steroids.
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Affiliation(s)
- Xiaoliang Wang
- Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA
| | - Joseph I Shapiro
- Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA.
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Alfieri C, Ruzhytska O, Vettoretti S, Caldiroli L, Cozzolino M, Messa P. Native Hypovitaminosis D in CKD Patients: From Experimental Evidence to Clinical Practice. Nutrients 2019; 11:E1918. [PMID: 31443249 PMCID: PMC6723756 DOI: 10.3390/nu11081918] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Revised: 08/07/2019] [Accepted: 08/12/2019] [Indexed: 12/12/2022] Open
Abstract
Native hypovitaminosis D (n-hVITD) is frequently found from the early stages of chronic kidney disease (CKD) and its prevalence increases with CKD progression. Even if the implications of n-hVITD in chronic kidney disease-mineral bone disorder (CKD-MBD) have been extensively characterized in the literature, there is a lot of debate nowadays about the so called "unconventional effects" of native vitamin D (25(OH)VitD) supplementation in CKD patients. In this review, highlights of the dimension of the problem of n-hVITD in CKD stages 2-5 ND patients will be presented. In addition, it will focus on the "unconventional effects" of 25(OH)VitD supplementation, the clinical impact of n-hVITD and the most significant interventional studies regarding 25(OH)VitD supplementation in CKD stages 2-5 ND.
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Affiliation(s)
- Carlo Alfieri
- Nephrology, Dialysis and Renal Transplantation, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
- Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy
| | - Oksana Ruzhytska
- Department of Internal Medicine n3, Ternopil State Medical University, 46002 Ternopil, Ukraine
| | - Simone Vettoretti
- Nephrology, Dialysis and Renal Transplantation, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Lara Caldiroli
- Nephrology, Dialysis and Renal Transplantation, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Mario Cozzolino
- Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy
- Renal Division, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, 20122 Milan, Italy
| | - Piergiorgio Messa
- Nephrology, Dialysis and Renal Transplantation, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.
- Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy.
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Kleine CE, Obi Y, Streja E, Hsiung JT, Park C, Holick MF, Kalantar-Zadeh K. Seasonal variation of serum 25-hydroxyvitamin D and parameters of bone and mineral disorder in dialysis patients. Bone 2019; 124:158-165. [PMID: 30858148 DOI: 10.1016/j.bone.2019.03.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2018] [Revised: 02/20/2019] [Accepted: 03/04/2019] [Indexed: 12/18/2022]
Abstract
BACKGROUND Vitamin D deficiency is common among dialysis patients and may impact blood concentrations of calcium, phosphorus, intact parathyroid hormone (iPTH), and alkaline phosphatase (ALP). Seasonal variation of serum 25-hydroxyvitamin D [25(OH)D] concentrations has been well established for the general population; however, less is known about circannual variation in 25(OH)D as well as other parameters of mineral and bone disorder among dialysis patients. METHOD Based on 57,500 serum 25(OH)D measurements collected over two years from January 2009 to December 2010 among 25,025 dialysis patients, we evaluated the circannual variations in serum concentrations of 25(OH)D, calcium, phosphorus, iPTH, and ALP by a linear regression model with a cosinor function for the time period (month). We adjusted for potential confounders including case-mix variables, and ultraviolet index. RESULTS Serum 25(OH)D concentrations showed significant circannual variation and mean serum 25(OH)D was 3.2 ng/mL higher in summer than in winter. Furthermore, 25(OH)D concentration increased steadily by 1.3 ng/mL per year. While serum calcium concentrations showed statistically significant but clinically negligible seasonal variation (0.02 mg/dL in peak-trough difference), serum phosphorus did not follow such a pattern. Serum iPTH concentrations also showed a modest seasonal variation with 9% higher values in winter than in summer. Concordantly, ALP concentrations in the winter were 2% higher than in the summer time. Seasonal variation of 25(OH)D was greater in male (vs. female), African-American (vs. non-African-American), and younger (vs. older) dialysis patients. CONCLUSION Serum 25(OH)D and iPTH concentrations show seasonal variation among dialysis patients while the variation in other parameters of mineral and bone disorder was clinically irrelevant, if any. Serum 25(OH)D also showed a gradual increase over time. Clinicians and researchers should be aware of these changes when interpreting laboratory results in dialysis patients.
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Affiliation(s)
- Carola-Ellen Kleine
- Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine, Orange, CA, USA; Long Beach Veterans Affairs Healthcare System, Long Beach, CA, USA
| | - Yoshitsugu Obi
- Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine, Orange, CA, USA; Long Beach Veterans Affairs Healthcare System, Long Beach, CA, USA
| | - Elani Streja
- Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine, Orange, CA, USA; Long Beach Veterans Affairs Healthcare System, Long Beach, CA, USA
| | - Jui-Ting Hsiung
- Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine, Orange, CA, USA; Long Beach Veterans Affairs Healthcare System, Long Beach, CA, USA
| | - Christina Park
- Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine, Orange, CA, USA; Long Beach Veterans Affairs Healthcare System, Long Beach, CA, USA
| | - Michael F Holick
- Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Kamyar Kalantar-Zadeh
- Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine, Orange, CA, USA; Long Beach Veterans Affairs Healthcare System, Long Beach, CA, USA.
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Prasad-Reddy L, Isaacs D, Kantorovich A. Considerations and controversies in managing chronic kidney disease: An update. Am J Health Syst Pharm 2019; 74:795-810. [PMID: 28546302 DOI: 10.2146/ajhp160559] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
PURPOSE Current considerations and controversies surrounding the management of chronic kidney disease (CKD) are reviewed. SUMMARY Patients diagnosed with CKD require a unique clinical approach to prevent medication toxicities and ensure appropriate management of disease-progressing comorbidities, and they require attention to commonly occurring complications that may affect disease control and impact quality of life, including anemia and CKD-bone-mineral disorder (CKD-BMD). Many CKD-related comorbidities put patients at increased cardiovascular risk, including diabetes, hypertension, and hyperlipidemia. Although there are clinical guidelines to help clinicians manage CKD and its related complications and comorbidities, there are many clinical controversies surrounding optimal treatment. Recent literature and clinical studies bring into question multiple controversies regarding the optimal management approach to the patient living with CKD, including the appropriateness of iron and erythropoiesis-stimulating agents (ESAs) for the treatment of anemia and vitamin D supplementation for the prevention of CKD-BMD. While available guidelines can provide clinicians with guidance regarding the appropriate management of the patient with CKD, they often differ dramatically in the optimal approach to the management of comorbidities and complications. For a patient with CKD, the pharmacist has an important role to ensure optimal outcomes, by appropriately managing comorbid conditions and optimizing drug dosing. CONCLUSION Multiple controversies regarding the optimal management of patients with CKD, including the appropriateness of iron and ESAs for treatment of anemia and vitamin D supplementation for the prevention of CKD-BMD. Available guidelines differ dramatically in the optimal approach to the management of comorbidities and complications.
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Affiliation(s)
- Lalita Prasad-Reddy
- Chicago State University, Chicago, IL .,Rush University Medical Center, Chicago, IL.
| | | | - Alexander Kantorovich
- Chicago State University College of Pharmacy, Chicago, IL.,Advocate Christ Medical Center, Oak Lawn, IL
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Samaan F, Carvalho AB, Pillar R, Rocha LA, Cassiolato JL, Cuppari L, Canziani MEF. The Effect of Long-Term Cholecalciferol Supplementation on Vascular Calcification in Chronic Kidney Disease Patients With Hypovitaminosis D. J Ren Nutr 2019; 29:407-415. [PMID: 30686750 DOI: 10.1053/j.jrn.2018.12.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2018] [Revised: 12/06/2018] [Accepted: 12/10/2018] [Indexed: 12/18/2022] Open
Abstract
OBJECTIVE The role of vitamin D supplementation on vascular calcification (VC) in patients with chronic kidney disease (CKD) is controversial. The objective of this study was to evaluate the effects of long-term cholecalciferol supplementation on VC in nondialysis patients with CKD stages 3-4 with hypovitaminosis D. DESIGN AND METHODS Eighty patients aged 18-85 years with creatinine clearance between 15 and 60 mL/min/1.73 m2 and serum 25(OH)D level < 30 ng/mL were enrolled in a 18-month prospective study. Individuals with vitamin D insufficiency (25-hydroxyvitamin D [25(OH)D] level between 16 and 29 ng/mL) were included in a randomized, double-blind, two-arm study to receive cholecalciferol or placebo. Patients with vitamin D deficiency [25(OH)D < 15 ng/mL] were included in an observational study and mandatorily received cholecalciferol. The coronary artery calcium score was obtained by multislice computed tomography at baseline and the 18th month. RESULTS During the study, VC did not change in the treated insufficient group (418 [81-611] to 364 [232-817] AU, P = 0.25) but increased in the placebo group (118 [37-421] to 199 [49-490] AU, P = 0.01). The calcium score change was inversely correlated with 25(OH)D change (r = -0.45; P = 0.037) in the treated insufficient group but not in the placebo group. Renal function did not change in the insufficient, treated, and placebo groups. In multivariate analysis, there was no difference in VC progression between the treated and placebo insufficient groups (interaction P = 0.92). In the deficient group, VC progressed (265 [84-733] to 333 [157-745] AU; P = 0.006) and renal function declined (33 [26-43] to 23 [17-49] mL/min/1.73 m2; P = 0.04). The calcium score change was inversely correlated with cholecalciferol cumulative doses (r = -0.41; P = 0.048) and kidney function change (r = -0.43; P = 0.033) but not with 25(OH)D change (r = -0.08; P = 0.69). CONCLUSION Vitamin D supplementation did not attenuate VC progression in CKD patients with hypovitaminosis D. CONCLUSION Vitamin D supplementation did not attenuate VC progression in CKD patients with hypovitaminosis D.
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Affiliation(s)
- Farid Samaan
- Nephrology Division, Federal University of São Paulo, São Paulo, Brazil
| | | | - Roberta Pillar
- Nephrology Division, Federal University of São Paulo, São Paulo, Brazil
| | - Lillian A Rocha
- Nephrology Division, Federal University of São Paulo, São Paulo, Brazil
| | | | - Lilian Cuppari
- Nephrology Division, Federal University of São Paulo, São Paulo, Brazil
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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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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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Zand L, Kumar R. The Use of Vitamin D Metabolites and Analogues in the Treatment of Chronic Kidney Disease. Endocrinol Metab Clin North Am 2017; 46:983-1007. [PMID: 29080646 PMCID: PMC5977979 DOI: 10.1016/j.ecl.2017.07.008] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are associated with abnormalities in bone and mineral metabolism, known as CKD-bone mineral disorder. CKD and ESRD cause skeletal abnormalities characterized by hyperparathyroidism, mixed uremic osteodystrophy, osteomalacia, adynamic bone disease, and frequently enhanced vascular and ectopic calcification. Hyperparathyroidism and mixed uremic osteodystrophy are the most common manifestations due to phosphate retention, reduced concentrations of 1,25-dihydroxyvitamin D, intestinal calcium absorption, and negative calcium balance. Treatment with 1-hydroxylated vitamin D analogues is useful.
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Affiliation(s)
- Ladan Zand
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55901, USA.
| | - Rajiv Kumar
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55901, USA; Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First Street SW, Rochester, MN 55901, USA.
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Abstract
Cardiovascular factors are an important cause of mortality in chronic kidney disease, and vitamin-D deficiency is common in this patient population. Therefore, we aimed to investigate the effect of oral cholecalciferol on cardiac mechanics in children with chronic kidney disease. A total of 41 children with chronic kidney disease - the patient group - and 24 healthy subjects - the control group - free of any underlying cardiac or renal disease with low 25-hydroxyvitamin-D3 levels were evaluated by conventional tissue Doppler imaging and two-dimensional speckle-tracking echocardiography, both at baseline and following Stoss vitamin-D supplementation. Left ventricular strain and strain rate values were compared between the study groups. Initial longitudinal and radial strain as well as strain rate values of the left ventricle were significantly lower in patients. After vitamin-D supplementation, these improved significantly in patients, whereas no significant change was observed in the control group. Our study showed that, although conventional and tissue Doppler imaging methods could not determine any effect, two-dimensional speckle-tracking echocardiography revealed the favourable effects of high-dose cholecalciferol on cardiac mechanics, implying the importance of vitamin-D supplementation in children with chronic kidney disease.
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Batacchi Z, Robinson-Cohen C, Hoofnagle AN, Isakova T, Kestenbaum B, Martin KJ, Wolf MS, de Boer IH. Effects of Vitamin D 2 Supplementation on Vitamin D 3 Metabolism in Health and CKD. Clin J Am Soc Nephrol 2017; 12:1498-1506. [PMID: 28768705 PMCID: PMC5586563 DOI: 10.2215/cjn.00530117] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2017] [Accepted: 05/25/2017] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND OBJECTIVES Vitamin D supplements are prescribed to correct low circulating concentrations of 25-hydroxyvitamin D. In CKD, vitamin D metabolism is complicated by decreased conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D by CYP27B1 and possibly decreased conversion of 25-hydroxyvitamin D to 24,25-dihydroxyvitamin D by CYP24A1. The aim of this study was to determine the effects of vitamin D2 supplementation on vitamin D metabolism in health and CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We conducted a treatment-only intervention study of 25 individuals with CKD (eGFR<60 ml/min per 1.73 m2) and 44 individuals without CKD from three academic centers, all with screening 25-hydroxyvitamin D <30 ng/ml. Each participant was prescribed vitamin D2 (ergocalciferol) 50,000 IU orally twice weekly for 5 weeks. We tested whether changes in plasma concentrations of vitamin D metabolites and vitamin D metabolic ratios differed by CKD status. Plasma 1,25-dihydroxyvitamin D3-to-25-hydroxyvitamin D3 ratio and 24,25-dihydroxyvitamin D3-to-25-hydroxyvitamin D3 ratio were calculated as estimates of CYP27B1 and CYP24A1 function, respectively. RESULTS With treatment, plasma 25-hydroxyvitamin D2 and total 25-hydroxyvitamin D concentrations increased similarly for participants with and without CKD. For participants without CKD, 1,25-dihydroxyvitamin D2 increased (2.8±1.3-32.9±1.4 pg/ml), whereas 1,25-dihydroxyvitamin D3 decreased (45.6±1.9-14.6±1.9 pg/ml), resulting in no significant change in total 1,25-dihydroxyvitamin D; 1,25-dihydroxyvitamin D3-to-25-hydroxyvitamin D3 ratio decreased (3.0±0.2-1.7±0.2 pg/ng), and 24,25-dihydroxyvitamin D3-to-25-hydroxyvitamin D3 ratio increased (115.7±7.8-195.2±7.9 pg/ng). Individuals with CKD had lower baseline levels and smaller changes in magnitude for 1,25-dihydroxyvitamin D2 (2.1±1.6-24.4±1.6 pg/ml; P interaction =0.01), 1,25-dihydroxyvitamin D3-to-25-hydroxyvitamin D3 ratio (1.8±0.2-1.1±0.2 pg/ng; P interaction =0.05), and 24,25-dihydroxyvitamin D3-to-25-hydroxyvitamin D3 ratio (72.0±9.1-110.3±9.3 pg/ng; P interaction <0.001). Fibroblast growth factor-23 and parathyroid hormone were not significantly changed in either group. CONCLUSIONS Vitamin D2 supplementation decreases conversion of 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3 and induces vitamin D3 catabolism as evidenced by changes in D3 metabolites and vitamin D metabolic ratios. These effects occur without significant changes in fibroblast growth factor-23 or parathyroid hormone and are blunted in CKD. PODCAST This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2017_08_02_CJASNPodcast_17_09.mp3.
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Affiliation(s)
- Zona Batacchi
- Divisions of Metabolism, Endocrinology and Nutrition and
- Kidney Research Institute, and
| | | | - Andrew N. Hoofnagle
- Divisions of Metabolism, Endocrinology and Nutrition and
- Kidney Research Institute, and
- Department of Laboratory Medicine, University of Washington, Seattle, Washington
| | - Tamara Isakova
- Division of Nephrology and Hypertension, Department of Medicine and
- Center for Translational Metabolism and Health, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | | | - Kevin J. Martin
- Division of Nephrology, St. Louis University, St. Louis, Missouri
| | - Myles S. Wolf
- Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina; and
| | - Ian H. de Boer
- Nephrology
- Kidney Research Institute, and
- Veterans Affairs Puget Sound Health Care System, Seattle, Washington
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Han N, Hong SH, Kim YS, Kim DK, Kim IW, Ji E, Oh JM. Effect of additive calcium administration on FGF23 levels in patients with mild chronic kidney disease treated with calcitriol: a randomized, open-labeled clinical trial. Ther Clin Risk Manag 2017; 13:999-1007. [PMID: 28860784 PMCID: PMC5565373 DOI: 10.2147/tcrm.s142564] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND The purpose of the present study was to determine the effect of additional calcium carbonate treatment on fibroblast growth factor 23 (FGF23) levels in patients treated with calcitriol. METHODS In this randomized, open-labeled, and parallel-group study, a total of 30 patients with early chronic kidney disease (CKD) and vitamin D deficiency were randomly assigned to two groups and received interventions for 8 weeks: 1) a combination of calcium carbonate and calcitriol group; and 2) calcitriol only group. The primary outcome was the difference in percentage change of serum FGF23 levels from baseline between the two groups. Secondary end points included the changes in serum levels of calcium, phosphate, parathyroid hormone (PTH), and 25-hydroxyvitamin D3 (25(OH)D) from baseline. RESULTS Serum FGF23 levels were more elevated in the combination group than in the calcitriol-alone group. However, both mean change and percentage change in the serum FGF23 levels during the 8-week period were not significantly different between the two groups. Serum calcium level was increased significantly only in the combination treatment group. There was no significant difference in percentage change of serum calcium levels between the two groups. In addition, changes in serum levels of phosphate, 25(OH)D, or PTH were not significantly different between the two groups. In correlation analysis, changes in serum FGF23 levels were positively correlated with changes in serum calcium and phosphate levels, but not with changes in 25(OH)D or PTH levels. No serious adverse events were observed, however, there was one case of mild gastrointestinal discomfort. CONCLUSION This study revealed that additional calcium carbonate treatment significantly increased serum FGF23 levels in patients treated with calcitriol, with their synergistic effect in promoting intestinal calcium absorption. This suggests that serum FGF23 levels should be monitored regularly, especially in those who use combination of vitamin D and calcium carbonate from the early stages of CKD.
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Affiliation(s)
- Nayoung Han
- Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul
| | - Su Hyun Hong
- Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul.,Pharmaceutical Standardization Division, Drug Evaluation Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Chungcheongbuk-do
| | - Yon Su Kim
- Division of Nephrology, Department of Internal Medicine, Seoul National University Hospital, Seoul
| | - Dong Ki Kim
- Division of Nephrology, Department of Internal Medicine, Seoul National University Hospital, Seoul
| | - In-Wha Kim
- Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul
| | - Eunhee Ji
- College of Pharmacy, Gachon University, Incheon, Republic of Korea
| | - Jung Mi Oh
- Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul
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Oh TR, Kim CS, Bae EH, Ma SK, Han SH, Sung SA, Lee K, Oh KH, Ahn C, Kim SW. Association between vitamin D deficiency and health-related quality of life in patients with chronic kidney disease from the KNOW-CKD study. PLoS One 2017; 12:e0174282. [PMID: 28448520 PMCID: PMC5407618 DOI: 10.1371/journal.pone.0174282] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2016] [Accepted: 03/06/2017] [Indexed: 12/25/2022] Open
Abstract
Vitamin D deficiency is a growing health problem in both the general population and in patients with chronic kidney disease (CKD). However, the relationship between serum 25-hydroxyvitamin D levels and health-related quality of life in CKD is not well established. This study examined the association between vitamin D deficiency and quality of life in pre-dialysis CKD patients. Serum 25-hydroxyvitamin D levels and the Korean version of the Kidney Disease Quality of Life short form were obtained for 1844 pre-dialysis CKD patients in the prospective KoreaN cohort Study for Outcomes in patients With Chronic Kidney Disease (KNOW-CKD). The baseline estimated glomerular filtration rate was 50.26 ± 0.71 mL/min/1.73 m2. We identified 1294 (70.2%) patients with vitamin D deficiency, defined as a 25-hydroxyvitamin D level < 20 ng/ml. The scores of the kidney disease component summary, physical component summary, and mental component summary in the vitamin D deficiency group were significantly lower compared to the scores of those without vitamin D deficiency. The serum 25-hydroxyvitamin D level was independently associated with the kidney disease component summary and mental component summary scores (β = 0.147, p = 0.003 and β = 0.151, p = 0.047). In conclusion, there was a significant association between serum 25-hydroxyvitamin D levels and kidney disease component summary and mental component summary scores in pre-dialysis CKD patients.
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Affiliation(s)
- Tae Ryom Oh
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Chang Seong Kim
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Eun Hui Bae
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Seong Kwon Ma
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Seung Hyeok Han
- Depatment of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Su-Ah Sung
- Department of Internal Medicine, Eulji University, Seoul, Korea
| | - Kyubeck Lee
- Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, Seoul, Korea
| | - Kook Hwan Oh
- Department of Internal Medicine, Seoul National University, Seoul, Korea
| | - Curie Ahn
- Department of Internal Medicine, Seoul National University, Seoul, Korea
| | - Soo Wan Kim
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
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Vitamin D deficiency is significantly associated with depression in patients with chronic kidney disease. PLoS One 2017; 12:e0171009. [PMID: 28192445 PMCID: PMC5305247 DOI: 10.1371/journal.pone.0171009] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2016] [Accepted: 01/14/2017] [Indexed: 11/21/2022] Open
Abstract
Background Depression is reported to be the most common psychological problem in patients with chronic kidney disease (CKD). Several studies have reported that lower levels of serum vitamin D are significantly associated with depression. Both vitamin D deficiency and depression are prevalent in patients with CKD, yet the relationship between these two factors remains poorly understood. This study aimed to investigate the association between vitamin D levels and depression among CKD patients. Methods Totally, 21,257 individuals who participated in the Korean National Health and Nutrition Examination Survey (KNHANES V, VI) from 2010–2014 were screened for the study; 533 CKD patients were included. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D3 [25(OH)D3] ≤10 ng/mL. Patients were divided into vitamin D deficient or sufficient groups. Depression was screened for using the Korean version of the WHO Composite International Diagnostic Interview-Short Form. The association between vitamin D deficiency and depression was evaluated by multivariate logistic regression analysis. Results The mean participant age was 70.1±9.4 years; 262 patients (49.2%) were male. The median 25(OH)D3 level was 19.1±6.9 ng/mL. The prevalence of depression was higher in CKD patients than in the general population (14.3 vs. 11.1%, P = 0.03). Additionally, the prevalence of depression was significantly higher in CKD patients with (vs. without) vitamin D deficiency (32.5% vs. 50.0%, P<0.001). Multivariate logistic regression analysis showed that vitamin D deficiency was a significant independent predictor of depression after adjusting for confounding factors (adjusted odds ratio, 6.15; 95% confidence interval, 2.02–8.75; P = 0.001). Conclusion Depression was highly prevalent in CKD patients, in whom vitamin D deficiency was a significant independent predictor of depression. Therefore, management of vitamin D deficiency might help prevent depression in CKD patients.
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Felício JS, Luz RM, de Melo FTC, de Souza Resende F, de Oliveira AF, Peixoto AS, Abrahão Neto JF, Carvalho CT, da Silva DD, dos Santos MC, de Queiroz NNM, de Lemos MN, Yamada ES, Felício KM. Vitamin D on Early Stages of Diabetic Kidney Disease: A Cross-sectional Study in Patients with Type 1 Diabetes Mellitus. Front Endocrinol (Lausanne) 2016; 7:149. [PMID: 28018288 PMCID: PMC5151807 DOI: 10.3389/fendo.2016.00149] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2016] [Accepted: 11/08/2016] [Indexed: 12/31/2022] Open
Abstract
CONTEXT Genetic and environmental factors are involved in the pathogenesis of type 1 diabetes mellitus (T1DM), and vitamin D (VD) deficiency appears as a candidate to risk factor for developing diabetic kidney disease (DKD). OBJECTIVE The purpose of study was to evaluate the existence of an association between low levels of VD and the presence and degree of DKD in T1DM. PATIENTS AND METHODS We performed a cross-sectional study, between November 2014 and December 2015. Levels of 25(OH)D and albuminuria were analyzed in 37 patients with T1DM and normal glomerular filtration rate. Thirty-six subjects were evaluated as a control group. RESULTS Patients with T1DM and hypovitaminosis D had higher levels of albuminuria compared to those with normal VD levels [albuminuria (log10) = 1.92 vs. 1.44; p < 0.05]. When we have separated the group of patients according to stage of DKD in patients with normo, micro, and macroalbuminuria, there are lower levels of 25(OH)D in the last when compared to the first two groups (26.7 ± 6.2, 24.8 ± 7.0, and 15.9 ± 7.6 ng/ml; p < 0.05, respectively). In T1DM group, we have found correlations between VD levels and both albuminuria and DKD stages (r = -0.5; p < 0.01 and r = -0.4; p < 0.05, respectively). A simple linear regression model, with albuminuria as the dependent variable and VD as an independent variable, showed r2 = 0.2 and p < 0.01. CONCLUSION Our data suggest an association between reduced levels of VD and the presence and severity of DKD.
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Affiliation(s)
- João Soares Felício
- Endocrinology Division, University Hospital João de Barros Barreto, Federal University of Pará, Belém, Pará, Brazil
| | - Rafael Mendonça Luz
- Endocrinology Division, University Hospital João de Barros Barreto, Federal University of Pará, Belém, Pará, Brazil
| | | | - Fabricio de Souza Resende
- Endocrinology Division, University Hospital João de Barros Barreto, Federal University of Pará, Belém, Pará, Brazil
| | - Alana Ferreira de Oliveira
- Endocrinology Division, University Hospital João de Barros Barreto, Federal University of Pará, Belém, Pará, Brazil
| | - Amanda Soares Peixoto
- Endocrinology Division, University Hospital João de Barros Barreto, Federal University of Pará, Belém, Pará, Brazil
| | - João Felício Abrahão Neto
- Endocrinology Division, University Hospital João de Barros Barreto, Federal University of Pará, Belém, Pará, Brazil
| | - Carolina Tavares Carvalho
- Endocrinology Division, University Hospital João de Barros Barreto, Federal University of Pará, Belém, Pará, Brazil
| | - Denisson Dias da Silva
- Endocrinology Division, University Hospital João de Barros Barreto, Federal University of Pará, Belém, Pará, Brazil
| | - Marcia Costa dos Santos
- Endocrinology Division, University Hospital João de Barros Barreto, Federal University of Pará, Belém, Pará, Brazil
| | | | - Manuela Nascimento de Lemos
- Endocrinology Division, University Hospital João de Barros Barreto, Federal University of Pará, Belém, Pará, Brazil
| | - Elizabeth Sumi Yamada
- Endocrinology Division, University Hospital João de Barros Barreto, Federal University of Pará, Belém, Pará, Brazil
| | - Karem Miléo Felício
- Endocrinology Division, University Hospital João de Barros Barreto, Federal University of Pará, Belém, Pará, Brazil
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Li XH, Huang XP, Pan L, Wang CY, Qin J, Nong FW, Luo YZ, Wu Y, Huang YM, Peng X, Yang ZH, Liao YH. Vitamin D deficiency may predict a poorer outcome of IgA nephropathy. BMC Nephrol 2016; 17:164. [PMID: 27806690 PMCID: PMC5094030 DOI: 10.1186/s12882-016-0378-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2016] [Accepted: 10/26/2016] [Indexed: 11/10/2022] Open
Abstract
Background Experimental studies showed that 25-hydroxy-vitamin D [25(OH)D] deficiency (defined as 25-hydroxy-vitamin D < 15 ng/ml) has been associated with CKD progression. Patients with IgA nephropathy have an exceptionally high rate of severe 25(OH)D deficiency; however, it is not known whether this deficiency is a risk factor for progression of IgA nephropathy. We conducted this study to investigate the relationship between the plasma level of 25(OH)D and certain clinical parameters and renal histologic lesions in the patients with IgA nephropathy, and to evaluate whether the 25(OH)D level could be a good prognostic marker for IgA nephropathy progression. Methods A total of 105 patients with biopsy-proven IgA nephropathy were enrolled between 2012 and 2015. The circulating concentration of 25(OH)D was determined using serum samples collected at the time of biopsy. The primary clinical endpoint was the decline of estimated glomerular filtration rate (eGFR; a 30 % or more decline compared to the baseline). Results Mean eGFR decreased and proteinuria worsened proportionally as circulating 25(OH)D decreased (P < 0.05). The 25(OH)D deficiency was correlated with a higher tubulointerstitial score by the Oxford classification (P = 0.008). The risk for reaching the primary endpoint was significantly higher in the patients with a 25(OH)D deficiency compared to those with a higher level of 25(OH)D (P = 0.001). As evaluated using the Cox proportional hazards model, 25(OH)D deficiency was found to be an independent risk factor for renal progression [HR 5.99, 95 % confidence intervals (CIs) 1.59–22.54, P = 0.008]. Conclusion A 25(OH)D deficiency at baseline is significantly correlated with poorer clinical outcomes and more sever renal pathological features, and low levels of 25(OH)D at baseline were strongly associated with increased risk of renal progression in IgAN. Electronic supplementary material The online version of this article (doi:10.1186/s12882-016-0378-4) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Xiao-Hua Li
- Renal Division, Department of Medicine, First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, China
| | - Xin-Ping Huang
- Renal Division, Department of Medicine, First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, China
| | - Ling Pan
- Renal Division, Department of Medicine, First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, China
| | - Cheng-Yu Wang
- Renal Division, Department of Medicine, First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, China
| | - Ju Qin
- Renal Division, Department of Medicine, First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, China
| | - Feng-Wei Nong
- Renal Division, Department of Medicine, First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, China
| | - Yu-Zhen Luo
- Renal Division, Department of Medicine, First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, China
| | - Yue Wu
- Renal Division, Department of Medicine, First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, China
| | - Yu-Ming Huang
- Renal Division, Department of Medicine, First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, China
| | - Xi Peng
- Renal Division, Department of Medicine, First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, China
| | - Zhen-Hua Yang
- Renal Division, Department of Medicine, First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, China
| | - Yun-Hua Liao
- Renal Division, Department of Medicine, First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, China.
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Căpuşa C, Stefan G, Stancu S, Ilyes A, Dorobanţu N, Mircescu G. Subclinical cardiovascular disease markers and vitamin D deficiency in non-dialysis chronic kidney disease patients. Arch Med Sci 2016; 12:1015-1022. [PMID: 27695492 PMCID: PMC5016586 DOI: 10.5114/aoms.2016.61911] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2015] [Accepted: 03/02/2015] [Indexed: 12/21/2022] Open
Abstract
INTRODUCTION Since 25-hydroxyvitamin D (25(OH)D) deficiency has been linked to an increased risk for cardiovascular disease (CVD) in the hemodialysis population, we aimed to determine the relationship between serum 25(OH)D level and markers of subclinical CVD in non-dialysis chronic kidney disease (CKD) patients. MATERIAL AND METHODS This cross-sectional, single-center study prospectively enrolled 87 clinically stable CKD patients (median age: 61 (57-66) years, 51% male, median estimated glomerular filtration rate (eGFR): 32 (27-37) ml/min). Five markers of subclinical CVD were assessed: intima-media thickness, abdominal aortic calcifications (AAC) using the Kauppila score, cardio-ankle vascular index, ankle-brachial index (ABI) and interventricular septum thickness. RESULTS Vascular (37%), glomerular (23%) and interstitial (18%) nephropathies were the main causes of CKD. 25(OH)D had a median value of 14 (12.5-17.1) ng/ml, and its levels decreased with eGFR (rs = 0.19; p = 0.04). Patients with 25(OH)D deficiency (54%) were older, had a higher serum alkaline phosphatase level, lower ABI and higher AAC score. There were no differences between the two groups regarding other traditional or non-traditional risk factors for atherosclerosis. The association between subclinical CVD markers and 25(OH)D was further evaluated in multivariable binomial logistic regression models adjusted for CV risk factors. Lower 25(OH)D level was retained as an independent predictor only for pathological ABI. CONCLUSIONS This is the first study to evaluate the relationship between a large set of subclinical CVD markers and 25(OH)D deficiency in non-dialysis CKD patients. We found that hypovitaminosis D is associated with subclinical peripheral arterial disease, independently of other cardiovascular risk factors.
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Affiliation(s)
- Cristina Căpuşa
- Nephrology Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- “Dr Carol Davila” Teaching Hospital of Nephrology, Bucharest, Romania
| | - Gabriel Stefan
- Nephrology Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- “Dr Carol Davila” Teaching Hospital of Nephrology, Bucharest, Romania
| | - Simona Stancu
- Nephrology Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- “Dr Carol Davila” Teaching Hospital of Nephrology, Bucharest, Romania
| | - Andrea Ilyes
- “Dr Carol Davila” Teaching Hospital of Nephrology, Bucharest, Romania
| | | | - Gabriel Mircescu
- Nephrology Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- “Dr Carol Davila” Teaching Hospital of Nephrology, Bucharest, Romania
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Molina P, Górriz JL, Molina MD, Beltrán S, Vizcaíno B, Escudero V, Kanter J, Ávila AI, Bover J, Fernández E, Nieto J, Cigarrán S, Gruss E, Fernández-Juárez G, Martínez-Castelao A, Navarro-González JF, Romero R, Pallardó LM. What is the optimal level of vitamin D in non-dialysis chronic kidney disease population? World J Nephrol 2016; 5:471-481. [PMID: 27648411 PMCID: PMC5011254 DOI: 10.5527/wjn.v5.i5.471] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2016] [Revised: 06/22/2016] [Accepted: 08/15/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate thresholds for serum 25(OH)D concentrations in relation to death, kidney progression and hospitalization in non-dialysis chronic kidney disease (CKD) population.
METHODS Four hundred and seventy non-dialysis 3-5 stage CKD patients participating in OSERCE-2 study, a prospective, multicenter, cohort study, were prospectively evaluated and categorized into 3 groups according to 25(OH)D levels at enrollment (less than 20 ng/mL, between 20 and 29 ng/mL, and at or above 30 ng/mL), considering 25(OH)D between 20 and 29 ng/mL as reference group. Association between 25(OH)D levels and death (primary outcome), and time to first hospitalization and renal progression (secondary outcomes) over a 3-year follow-up, were assessed by Kaplan-Meier survival curves and Cox-proportional hazard models. To identify 25(OH)D levels at highest risk for outcomes, receiver operating characteristic (ROC) curves were performed.
RESULTS Over 29 ± 12 mo of follow-up, 46 (10%) patients dead, 156 (33%) showed kidney progression, and 126 (27%) were hospitalized. After multivariate adjustment, 25(OH)D < 20 ng/mL was an independent predictor of all-cause mortality (HR = 2.33; 95%CI: 1.10-4.91; P = 0.027) and kidney progression (HR = 2.46; 95%CI: 1.63-3.71; P < 0.001), whereas the group with 25(OH)D at or above 30 ng/mL did not have a different hazard for outcomes from the reference group. Hospitalization outcomes were predicted by 25(OH) levels (HR = 0.98; 95%CI: 0.96-1.00; P = 0.027) in the unadjusted Cox proportional hazards model, but not after multivariate adjusting. ROC curves identified 25(OH)D levels at highest risk for death, kidney progression, and hospitalization, at 17.4 ng/mL [area under the curve (AUC) = 0.60; 95%CI: 0.52-0.69; P = 0.027], 18.6 ng/mL (AUC = 0.65; 95%CI: 0.60-0.71; P < 0.001), and 19.0 ng/mL (AUC = 0.56; 95%CI: 0.50-0.62; P = 0.048), respectively.
CONCLUSION 25(OH)D < 20 ng/mL was an independent predictor of death and progression in patients with stage 3-5 CKD, with no additional benefits when patients reached the levels at or above 30 ng/mL suggested as optimal by CKD guidelines.
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45
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Yang H, Luo H, Tang X, Zeng X, Yu Y, Ma L, Fu P. Prognostic value of FGF23 among patients with end-stage renal disease: a systematic review and meta-analysis. Biomark Med 2016; 10:547-56. [PMID: 27075973 DOI: 10.2217/bmm.16.11] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Aims: Prognostic value of FGF23 in end-stage renal disease (ESRD) patients is controversial. A systematic review was conducted to quantify the association between elevated FGF23 and overall mortality among ESRD patients. Methods: MEDLINE, EMBASE, PubMed and reference lists were searched. Quality of the included studies was evaluated using Newcastle–Ottawa Scale checklist. Pooled effects were calculated as hazard ratio using fixed-effect models, and chi-square test was used for heterogeneity testing. Results: Seven studies (1406 patients) were included. Patients were at mean age of 62.3. Mean follow-up was 29.4 months. From the pooled analysis, elevated FGF23 was significantly associated with increased all-cause mortality (hazard ratio: 1.53; 95% CI: 1.05–2.25). p-value for heterogeneity was 0.10, I2 = 48%. Conclusions: ESRD patients with elevated FGF23 concentration have higher risk of death.
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Affiliation(s)
- Hongliu Yang
- Division of Nephrology, Kidney Research Institute, West China Hospital, West China Medical School of Sichuan University, Chengdu, Sichuan, China
| | - Han Luo
- Division of Thyroid surgery, West China Hospital, West China Medical School of Sichuan University, Chengdu, Sichuan, China
| | - Xi Tang
- Division of Nephrology, Kidney Research Institute, West China Hospital, West China Medical School of Sichuan University, Chengdu, Sichuan, China
| | - Xiaoxi Zeng
- Division of Nephrology, Kidney Research Institute, West China Hospital, West China Medical School of Sichuan University, Chengdu, Sichuan, China
| | - Yang Yu
- Division of Nephrology, Kidney Research Institute, West China Hospital, West China Medical School of Sichuan University, Chengdu, Sichuan, China
| | - Liang Ma
- Division of Nephrology, Kidney Research Institute, West China Hospital, West China Medical School of Sichuan University, Chengdu, Sichuan, China
| | - Ping Fu
- Division of Nephrology, Kidney Research Institute, West China Hospital, West China Medical School of Sichuan University, Chengdu, Sichuan, China
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Nakashima A, Yokoyama K, Yokoo T, Urashima M. Role of vitamin D in diabetes mellitus and chronic kidney disease. World J Diabetes 2016; 7:89-100. [PMID: 26981182 PMCID: PMC4781904 DOI: 10.4239/wjd.v7.i5.89] [Citation(s) in RCA: 75] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2015] [Revised: 12/24/2015] [Accepted: 01/19/2016] [Indexed: 02/05/2023] Open
Abstract
Approximately 30%-50% of people are recognized to have low levels of vitamin D, and insufficiency and deficiency of vitamin D are recognized as global health problems worldwide. Although the presence of hypovitamin D increases the risk of rickets and fractures, low vitamin D levels are also associated with hypertension, cancer, and cardiovascular disease. In addition, diabetes mellitus (DM) and chronic kidney disease (CKD) are also related to vitamin D levels. Vitamin D deficiency has been linked to onset and progression of DM. Although in patients with DM the relationship between vitamin D and insulin secretion, insulin resistance, and β-cell dysfunction are pointed out, evidence regarding vitamin D levels and DM is contradictory, and well controlled studies are needed. In addition, vitamin D influences the renin-angiotensin system, inflammation, and mineral bone disease, which may be associated with the cause and progression CKD. There is increasing evidence that vitamin D deficiency may be a risk factor for DM and CKD; however, it remains uncertain whether vitamin D deficiency also predisposes to death from DM and CKD. Although at this time, supplementation with vitamin D has not been shown to improve glycemic control or prevent incident DM, clinical trials with sufficient sample size, study periods, and optimal doses of vitamin D supplementation are still needed. This review focuses on the mechanism of vitamin D insufficiency and deficiency in DM or CKD, and discusses the current evidence regarding supplementation with vitamin D in patients with these diseases.
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Aytaç MB, Deveci M, Bek K, Kayabey Ö, Ekinci Z. Effect of cholecalciferol on local arterial stiffness and endothelial dysfunction in children with chronic kidney disease. Pediatr Nephrol 2016; 31:267-77. [PMID: 26432706 DOI: 10.1007/s00467-015-3220-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2015] [Revised: 09/10/2015] [Accepted: 09/13/2015] [Indexed: 12/13/2022]
Abstract
BACKGROUND As cardiovascular factors are the leading cause of mortality in chronic kidney disease (CKD) and as vitamin D deficiency is prevalent in this population, we aimed to examine the effect of oral cholecalciferol on cardiac parameters and biomarkers for endothelial cell activation in children with CKD. METHODS Forty-one children with CKD and 24 healthy subjects free of any underlying cardiac or renal disease with low 25-hydroxyvitamin D3 (25OHD) levels were evaluated using echocardiography basally and following Stoss vitamin D supplementation. The local vascular stiffness and endothelial dysfunction markers were compared among the groups. RESULTS Initial flow-mediated dilatation (FMD) measurements were lower and local arterial stiffness was significantly higher in patients. After vitamin D supplementation, these improved significantly in patients, while no significant change was observed for the healthy group. Homocysteine showed inverse correlation with baseline vitamin D level in CKD children and von Willebrand factor emerged as an independent risk factor for FMD impairment. CONCLUSIONS Our interventional study revealed the favorable effects of high-dose cholecalciferol on cardiovascular and endothelial parameters, implying the importance of vitamin D supplementation in children with CKD.
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Affiliation(s)
- Mehmet Baha Aytaç
- Department of Pediatric Nephrology, Kocaeli University, Medical Faculty, Izmit, Turkey.
| | - Murat Deveci
- Department of Pediatric Cardiology, Kocaeli University, Medical Faculty, Izmit, Turkey
| | - Kenan Bek
- Department of Pediatric Nephrology, Kocaeli University, Medical Faculty, Izmit, Turkey
| | - Özlem Kayabey
- Department of Pediatric Cardiology, Kocaeli University, Medical Faculty, Izmit, Turkey
| | - Zelal Ekinci
- Department of Pediatric Nephrology and Rheumatology, Kocaeli University, Medical Faculty, Izmit, Turkey
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Fujii H, Nakai K, Yonekura Y, Kono K, Goto S, Hirata M, Shinohara M, Nishi S, Fukagawa M. The Vitamin D Receptor Activator Maxacalcitol Provides Cardioprotective Effects in Diabetes Mellitus. Cardiovasc Drugs Ther 2015; 29:499-507. [PMID: 26602563 DOI: 10.1007/s10557-015-6629-y] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
PURPOSE Recent reports showed a significant association between vitamin D levels and cardiovascular disease events and mortality. In the current study, we investigated the effect of the vitamin D receptor activator maxacalcitol (OCT) on cardiac damage in a rat model of type 2 diabetes. METHODS At 20 weeks of age, the rats were divided into three groups: vehicle-treated (DM), insulin-treated (INS) and OCT-treated (OCT). At 30 weeks, the rats were sacrificed and urinary and blood biochemical analyses and cardiac histological and immunohistochemical analyses were performed. To evaluate the effect of OCT on the renin-angiotensin system, we performed a further study using aliskiren (ALS). At 20 weeks, the diabetic rats were divided into two groups: the ALS-treated group (ALS) and the ALS plus OCT-treated group (ALS + OCT), and we evaluated the renin-angiotensin system (RAS) and cardiac lesions at 30 weeks. RESULTS At 30 weeks, despite comparable blood pressure and renal function, heart volume, intracardiac oxidative stress by immunohistological analysis, cardiac and perivascular fibrosis and urinary excretion of 8-hydroxydeoxyguanosine and serum N-terminal pro-brain natriuretic peptide levels were significantly decreased in the OCT group compared to the DM group. mRNA expressions of dihydronicotinamide adenine dinucleotide phosphate (NADPH) p47 subunit and cardiac injury-related markers in the heart were also significantly decreased in the OCT group compared to the DM group. The cardioprotective effect of OCT was preserved even in the context of RAS inhibition. CONCLUSION Our results suggest that OCT prevents the development of cardiac damage in DM, independent of RAS inhibition.
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Affiliation(s)
- Hideki Fujii
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.
| | - Kentaro Nakai
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Yuriko Yonekura
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Keiji Kono
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Shunsuke Goto
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Michinori Hirata
- Fuji Gotemba Research Labs, Chugai Pharmaceutical Co., Ltd, Shizuoka, Japan
| | | | - Shinichi Nishi
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Masafumi Fukagawa
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
- Division of Nephrology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan
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Le Fur A, Fournier MC, Gillaizeau F, Masson D, Giral M, Cariou B, Cantarovich D, Dantal J. Vitamin D deficiency is an independent risk factor for PTDM after kidney transplantation. Transpl Int 2015; 29:207-15. [DOI: 10.1111/tri.12697] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2015] [Revised: 04/14/2015] [Accepted: 09/25/2015] [Indexed: 01/05/2023]
Affiliation(s)
- Awena Le Fur
- Institute of Transplantation, Urology and Nephrology (ITUN); Nantes University Hospital; Nantes France
- INSERM UMR 1064; Nantes University Hospital; Nantes France
| | - Marie-Cécile Fournier
- INSERM UMR 1064; Nantes University Hospital; Nantes France
- EA 4275 - SPHERE Biostatistics, Pharmacoepidemiology, and Human Sciences Research; Nantes University Hospital; Nantes France
| | - Florence Gillaizeau
- Institute of Transplantation, Urology and Nephrology (ITUN); Nantes University Hospital; Nantes France
- INSERM UMR 1064; Nantes University Hospital; Nantes France
- EA 4275 - SPHERE Biostatistics, Pharmacoepidemiology, and Human Sciences Research; Nantes University Hospital; Nantes France
| | | | - Magali Giral
- Institute of Transplantation, Urology and Nephrology (ITUN); Nantes University Hospital; Nantes France
- INSERM UMR 1064; Nantes University Hospital; Nantes France
- EA 4275 - SPHERE Biostatistics, Pharmacoepidemiology, and Human Sciences Research; Nantes University Hospital; Nantes France
| | - Bertrand Cariou
- Endocrinology Clinic; Nantes University Hospital; Nantes France
- INSERM UMR 1087; CNRS UMR 6291; Thorax Institute; Nantes University Hospital; Nantes France
| | - Diego Cantarovich
- Institute of Transplantation, Urology and Nephrology (ITUN); Nantes University Hospital; Nantes France
- INSERM UMR 1064; Nantes University Hospital; Nantes France
| | - Jacques Dantal
- Institute of Transplantation, Urology and Nephrology (ITUN); Nantes University Hospital; Nantes France
- INSERM UMR 1064; Nantes University Hospital; Nantes France
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50
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[Vitamin D deficiency in childhood: an opportunity for prevention]. BOLETIN MEDICO DEL HOSPITAL INFANTIL DE MEXICO 2015; 72:225-234. [PMID: 29421141 DOI: 10.1016/j.bmhimx.2015.01.011] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2014] [Accepted: 01/27/2015] [Indexed: 01/12/2023] Open
Abstract
The prevalence of vitamin D deficiency in the pediatric population has increased in recent years and continues to be underdiagnosed and undertreated. According to data from the "ENSANUT 2006" (National Health and Nutrition Survey), the prevalence of vitamin D deficiency in Mexico was 16% in children aged 2-12 years. Vitamin D plays a critical role in the formation and bone homeostasis and consequently on growth. Its deficiency is clearly associated with diseases such as rickets and osteomalacia, and it has been linked to other diseases such as obesity, metabolic syndrome, diabetes, cancer, respiratory infections and immune system disease. Specific risk groups have been described in the medical literature for vitamin D deficiency in which supplementation may offer a benefit. Currently, there is still controversy in defining the serum levels of proficiency and dose supplementation. In Mexico, the daily suggested intake of vitamin D is 5.6μg (224 IU), which is significantly lower than the recommendations in the U.S. and Europe (i.e., between 400 and 1000 IU/day). An increase in vitamin D deficiency has been reported in recent years. There is no consensus regarding the sufficiency levels of vitamin D. Cut-off values vary from 20 to 30ng/ml. Therefore, the objective of this review was to provide an overview of the problem in the pediatric population and to describe the groups at risk, as well as to analyze the current recommendations for vitamin D supplementation. Vitamin D deficiency was considered rare in Mexico according to the National Institute of Medical Science and Nutrition Salvador Zubirán. Lack of evidence did not help to establish the international recommended daily intake. Currently, vitamin D deficiency must be recognized as a health problem, worthy of attention and action. We suggest that prospective studies are carried out in our country where the relationship between serum vitamin D deficiency and poor bone mineralization will be established.
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