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Yu J, Li Y, Zhu B, Shen J, Miao L. Vitamin D: an important treatment for secondary hyperparathyroidism in chronic kidney disease? Int Urol Nephrol 2024:10.1007/s11255-024-04334-9. [PMID: 39738859 DOI: 10.1007/s11255-024-04334-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Accepted: 12/18/2024] [Indexed: 01/02/2025]
Abstract
Secondary hyperparathyroidism (SHPT) is one of the most common complications of chronic kidney disease (CKD). Vitamin D levels begin to decrease in the early stages of CKD, and these vitamin D-related changes play a central role in the occurrence and development of SHPT. Vitamin D-based drugs, which inhibit parathyroid hormone secretion either directly or indirectly, are commonly used to treat SHPT. However, vitamin D-based drugs can also lead to a dysregulated balance between serum calcium and phosphorus, as well as other adverse reactions. Over the past several decades, researchers have conducted in-depth studies on the pathogenesis of SHPT, developed new vitamin D-based drugs, and explored combinatory methods to improve treatment efficacy for the disease. Here, we review vitamin D metabolism, the diagnosis of vitamin D deficiency in patients with CKD, the pathogenesis of SHPT, the pharmacological effects of vitamin D drugs, and the benefits and side effects of using vitamin D to treat SHPT.
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Affiliation(s)
- Jie Yu
- Department of Nephrology, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Yulu Li
- Department of Nephrology, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Bin Zhu
- Department of Critical Care Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Jianqin Shen
- Department of Blood Purification Center, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Liying Miao
- Department of Nephrology, The Third Affiliated Hospital of Soochow University, Changzhou, China.
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Mai Y, Yi Y, Wen Y, Huang P, Wang Y, Wang Z. Associations between serum 25-hydroxyvitamin D and prognosis of chronic kidney disease: a prospective cohort study. Int Urol Nephrol 2024; 56:3323-3334. [PMID: 38767811 DOI: 10.1007/s11255-024-04083-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2024] [Accepted: 05/16/2024] [Indexed: 05/22/2024]
Abstract
BACKGROUND AND OBJECTIVES 25-hydroxyvitamin D [25(OH)D] deficiency is prevalent in patients with chronic kidney disease (CKD), the associations between serum 25(OH)D levels and mortality in patients with CKD remain unclear, and this study aimed to explore these associations further. METHODS 4989 participants with CKD were enrolled in the study, and the Cox regression model was used to assess the effects of serum 25(OH)D concentrations on mortality risk. A restricted cubic spline model was used to explore the dose-response relationships, and threshold effect analysis was performed based on inflection points identified by a two-piecewise linear regression model. In addition, subgroup and sensitivity analyses were employed. RESULTS 1255 participants died during a mean follow-up period of 70 months. Compared with the 25(OH)D-deficient group, the fully adjusted hazard ratios and 95% confidence intervals for the 25(OH)D-adequate group were 0.631 (0.545, 0.730) for all-cause mortality, 0.569 (0.435, 0.743) for cardiovascular mortality, 0.637 (0.461, 0.878) for hypertension mortality, and cancer mortality was 0.596 (0.426, 0.834). The inflection points of serum 25(OH)D concentration affecting all-cause and cardiovascular mortality were 89 nmol/L, and 107 nmol/L, respectively. Subgroup analyses and interaction tests suggested that the effects varied across populations. The results of sensitivity analyses indicated a reliable correlation. CONCLUSION We found an association between serum 25(OH)D concentrations and the prognosis of patients with CKD as a reliable predictor of early intervention and intensive care.
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Affiliation(s)
- Yanpei Mai
- School of Medicine, South China University of Technology, Guangzhou, 510006, China.
| | - Yushan Yi
- School of Medicine, South China University of Technology, Guangzhou, 510006, China
| | - Yaqing Wen
- School of Medicine, South China University of Technology, Guangzhou, 510006, China
| | - Peixian Huang
- School of Medicine, South China University of Technology, Guangzhou, 510006, China
| | - Yuying Wang
- School of Medicine, South China University of Technology, Guangzhou, 510006, China
| | - Zhirui Wang
- School of Medicine, South China University of Technology, Guangzhou, 510006, China
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Yang CT, Yen HH, Su PY, Chen YY, Huang SP. High prevalence of vitamin D deficiency in Taiwanese patients with inflammatory bowel disease. Sci Rep 2024; 14:14091. [PMID: 38890510 PMCID: PMC11189481 DOI: 10.1038/s41598-024-64930-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2024] [Accepted: 06/14/2024] [Indexed: 06/20/2024] Open
Abstract
Vitamin D deficiency is common in patients with inflammatory bowel disease (IBD). In this study, we aimed to evaluate the prevalence and risk factors of vitamin D deficiency in a Taiwanese IBD cohort. Vitamin D levels were checked in adult patients with IBD who were treated at Changhua Christian Hospital, a medical center in central Taiwan, from January 2017 to December 2023. The risk factors for vitamin D deficiency were evaluated. 106 adult IBD patients were included, including 20 patients with Crohn's disease and 86 with ulcerative colitis. The median age at diagnosis was 39.2 years. The mean vitamin D level was 22.2 ± 8 ng/mL. Forty-five patients (42.5%) had vitamin D deficiency (vitamin D level < 20 ng/mL). Comparing patients with normal vitamin D levels and those with vitamin D deficiency after multivariate adjustment, female sex and early age at diagnosis were identified as statistically significant risk factors. We found a prevalence of 42.5% of vitamin D deficiency in the Taiwanese IBD population. Understanding this issue is essential for teaching patients and doctors about vitamin D deficiency screening and improving patient outcomes.
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Affiliation(s)
- Chen-Ta Yang
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, 400, Taiwan
- Division of Gastroenterology, Changhua Christian Hospital, Changhua, 500, Taiwan
| | - Hsu-Heng Yen
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, 400, Taiwan.
- Division of Gastroenterology, Changhua Christian Hospital, Changhua, 500, Taiwan.
| | - Pei-Yuan Su
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, 400, Taiwan
- Division of Gastroenterology, Changhua Christian Hospital, Changhua, 500, Taiwan
| | - Yang-Yuan Chen
- Division of Gastroenterology, Changhua Christian Hospital, Changhua, 500, Taiwan
- Department of Hospitality Management, MingDao University, Changhua, 500, Taiwan
| | - Siou-Ping Huang
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, 400, Taiwan
- Division of Gastroenterology, Changhua Christian Hospital, Changhua, 500, Taiwan
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Cameron LK, Ledwaba-Chapman L, Voong K, Hampson G, Forni LG, Seylanova N, Harrington DJ, Lim R, Bociek A, Yanzhong W, Ostermann M. Vitamin D metabolism in critically ill patients with acute kidney injury: a prospective observational study. Crit Care 2024; 28:108. [PMID: 38566240 PMCID: PMC10988948 DOI: 10.1186/s13054-024-04869-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Accepted: 03/11/2024] [Indexed: 04/04/2024] Open
Abstract
BACKGROUND Vitamin D deficiency in critically ill patients is associated with poor outcomes, and vitamin D supplementation is recommended for patients with chronic kidney disease. Whether acute kidney injury (AKI) is associated with altered Vitamin D metabolism is unknown. We aimed to compare the longitudinal profiles of serum 25(OH)D and 1,25(OH)2D concentrations in critically ill patients with and without moderate to severe AKI and explore the impact of renal recovery and parathyroid hormone (PTH). METHODS In this prospective, observational study in two centres in the UK, critically ill patients with and without AKI underwent serial measurement of serum 25(OH)D and 1,25(OH)2D and plasma PTH concentrations for 5 days. Linear mixed model analysis and sensitivity analyses were performed. RESULTS Serial data of 137 patients were analysed. Seventy-one patients had AKI stage II/III of whom 23 recovered kidney function during the 5-day study period; 66 patients did not have AKI at enrolment of whom 14 developed new AKI. On day of enrolment, patients' serum 25(OH)D concentrations were low (median 18 nmol/L) but there was no significant difference between patients with and without AKI. Median serum 1,25(OH)2D levels were significantly lower in patients with AKI II/III (41 pmol/L [IQR 26, 58]) compared to similarly unwell patients without AKI (54 pmol/L [IQR 33, 69]) during the 5-day period. Recovery of kidney function in patients with AKI was associated with a rise in 1,25(OH)2D concentrations. Plasma PTH results were impacted by serum calcium and magnesium levels but not associated with 1,25(OH)2D levels. CONCLUSIONS Critically ill patients with moderate-to-severe AKI have significantly lower serum 1,25(OH)2D concentrations than similarly sick patients without AKI but there was no difference in serum 25(OH)D concentrations. Recovery of AKI was associated with a rise in serum 1,25(OH)2D concentrations. More research is needed to investigate the health benefits and safety of supplementation with active vitamin D in critically ill patients with moderate-to-severe AKI. Trial registration Clinicaltrials.gov (NCT02869919), registered on 16 May 2016.
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Affiliation(s)
- Lynda K Cameron
- Department of Critical Care, King's College London, Guy's and St Thomas' NHS Foundation Trust, London, SE1 7EH, UK
- Pharmacy Department, Guy's and St Thomas' NHS Foundation Trust, London, UK
- Institute of Pharmaceutical Sciences, School of Cancer and Pharmacy, King's College London, London, SE1 9RT, UK
| | - Lesedi Ledwaba-Chapman
- Department of Population Health Sciences, King's College London, Addison House, Guy's Campus, London, SE1 1UL, UK
| | - Kieran Voong
- Nutristasis Unit, Synnovis, Guy's and St. Thomas' NHS Foundation Trust, London, UK
| | - Geeta Hampson
- Department of Chemical Pathology and Metabolic Medicine, St Thomas' Hospital, Lambeth Palace Road, London, SE1 7EH, UK
- Department of Diabetes and Endocrinology, Metabolic Bone Clinic, St Thomas' Hospital, London, UK
| | - Lui G Forni
- Department of Critical Care, Royal Surrey Foundation Trust, Guildford, Surrey, UK
- School of Medicine, University of Surrey, Guildford, Surrey, UK
| | - Nina Seylanova
- Department of Critical Care, King's College London, Guy's and St Thomas' NHS Foundation Trust, London, SE1 7EH, UK
| | - Dominic J Harrington
- Nutristasis Unit, Synnovis, Guy's and St. Thomas' NHS Foundation Trust, London, UK
| | - Rosario Lim
- Department of Critical Care, King's College London, Guy's and St Thomas' NHS Foundation Trust, London, SE1 7EH, UK
| | - Aneta Bociek
- Department of Critical Care, King's College London, Guy's and St Thomas' NHS Foundation Trust, London, SE1 7EH, UK
| | - Wang Yanzhong
- Department of Population Health Sciences, King's College London, Addison House, Guy's Campus, London, SE1 1UL, UK
| | - Marlies Ostermann
- Department of Critical Care, King's College London, Guy's and St Thomas' NHS Foundation Trust, London, SE1 7EH, UK.
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Kassianides X, Bhandari S. The differential effect of modern intravenous iron on fibroblast growth factor 23 and phosphate in non-dialysis dependent CKD - the exploratory randomized controlled double-blind ExplorIRON-CKD study. BMC Nephrol 2024; 25:54. [PMID: 38347520 PMCID: PMC10860218 DOI: 10.1186/s12882-023-03440-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Accepted: 12/14/2023] [Indexed: 02/15/2024] Open
Abstract
BACKGROUND Intravenous iron is commonly used in patients with non-dialysis-dependent chronic kidney disease (CKD). Modern intravenous iron compounds (e.g. ferric derisomaltose (FDI), ferric carboxymaltose (FCM)) are increasingly utilized with similar efficacy. A differential effect in terms of hypophosphatemia has been noted following administration of FCM, which may be related to fibroblast growth factor 23 (FGF23). This study was designed to examine the comparative effects of FDI and FCM on FGF23, phosphate and other markers of bone turnover. METHODS The single-center double-blind randomized controlled trial "Iron and Phosphaturia - ExplorIRON-CKD" primarily assessed the effects of FCM and FDI on intact FGF23 and phosphate, whilst also studying the impact on vitamin D, parathyroid hormone and phosphaturia. Bone markers including alkaline phosphatase, bone-specific alkaline phosphatase, procollagen type 1 N-terminal propeptide and carboxy-terminal collagen cross-linked telopeptide were monitored. Non-dialysis-dependent CKD patients (stage 3a-5) with iron deficiency with/without anemia (serum ferritin < 200 µg/L or transferrin saturation = 20% and serum ferritin 200-299 µg/L) were randomized to receive FDI or FCM in a 1:1 ratio. At baseline 1000 mg of intravenous iron was administered followed by 500-1000 mg at 1 month to achieve replenishment. Measurements were performed at baseline, 1-2 days following iron administration, 2 weeks, 1 month (second iron administration), 1-2 days following second administration, 2 months and 3 months following initial infusion. RESULTS Twenty-six patients participated in the trial; 14 randomized to FDI and 12 to FCM. Intact FGF23 increased following administration of iron, and the increase was significantly higher with FCM compared to FDI (Baseline to 1-2 days following 1st administration: FDI: 3.0 (IQR: - 15.1 - 13.8) % vs. FCM: 146.1 (IQR: 108.1-203.1) %; p < 0.001 and Baseline to 1-2 days following 2nd administration: FDI: 3.2 (IQR: - 3.5 - 25.4) % vs. FCM: 235.1 (138.5-434.6) %; p = 0.001). Phosphate levels decreased in the FCM group, causing a significant difference versus FDI 2 weeks following administration of the first dose. A significantly greater decrease in 1,25 (OH)2 Vitamin D was noted with FCM. Several markers of bone turnover significantly changed following administration of FCM but not FDI. CONCLUSIONS The study suggests a differential effect on FGF23 following administration of FCM compared to FDI in non-dialysis-dependent CKD patients, similar to other patient groups. This may lead to changes consistent with hypovitaminosis D and alterations in bone turnover with potential clinical consequences. Further definitive studies are required to understand these differences of intravenous iron compounds. TRIAL REGISTRATION European Union Drug Regulating Authorities Clinical Trials Database (EudraCT) number: 2019-004370-26 ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-004370-26/GB ) (First date of trial registration: 03/12/2019).
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Affiliation(s)
- Xenophon Kassianides
- Academic Renal Research Department, Hull University Teaching Hospitals NHS Trust and the Hull York Medical School, Kingston upon Hull, UK.
| | - Sunil Bhandari
- Academic Renal Research Department, Hull University Teaching Hospitals NHS Trust and the Hull York Medical School, Kingston upon Hull, UK
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Molina P, Molina MD, Carrero JJ, Escudero V, Torralba J, Castro-Alonso C, Beltrán S, Vizcaíno B, González-Moya M, Kanter J, Sancho-Calabuig A, Bover J, Górriz JL. Sevelamer Use and Mortality in People with Chronic Kidney Disease Stages 4 and 5 Not on Dialysis. J Clin Med 2023; 12:7631. [PMID: 38137700 PMCID: PMC10743559 DOI: 10.3390/jcm12247631] [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: 11/01/2023] [Revised: 11/27/2023] [Accepted: 12/07/2023] [Indexed: 12/24/2023] Open
Abstract
Rationale and objective: Data suggest that non-calcium-based binders, and specifically sevelamer, may lead to lower rates of death when compared with calcium-based binders in end-stage renal disease (ESRD) patients. However, the association between sevelamer use and mortality for those with non-dialysis-dependent chronic kidney disease (NDD-CKD) patients has been uncertain. Study design: Our research is presented in a prospective cohort study. Setting and participants: A total of 966 participants with NDD-CKD stages 4-5 were enrolled in the PECERA study from 12 centers in Spain. Exposure: The participants were treated with sevelamer. Outcome: This study yielded all-cause and cardiovascular mortality outcomes. Analytical approach: We conducted an association analysis between mortality and sevelamer use with time-dependent Cox proportional hazards models. Results: After a median follow-up of 29 months (IQR: 13-36 months), death occurred in 181 participants (19%), with cardiovascular (n = 95, 53%) being the leading cause of death. In a multivariable model, the adjusted hazard ratios (HRs) for patients under sevelamer treatment were 0.44 (95% CI, 0.22 to 0.88) and 0.37 (95% CI, 0.18 to 0.75) for all-cause and cardiovascular mortality, respectively, compared with those of untreated patients. Limitations: Some limitations include potential confusion via indication bias; causal statements about these associations cannot be made due to the observational nature of this study. Conclusions: In this prospective NDD-CKD cohort study, the administration of sevelamer was independently associated with lower all-cause and cardiovascular mortality, suggesting that non-calcium-based phosphate binders might be the first-line therapy for phosphate lowering in this population. Further interventional studies clarifying the risks and benefits of phosphate binders in NDD-CKD are warranted.
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Affiliation(s)
- Pablo Molina
- Department of Nephrology, Hospital Universitari Dr. Peset, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana, 46017 Valencia, Spain; (V.E.); (C.C.-A.); (S.B.); (B.V.); (M.G.-M.); (J.K.); (A.S.-C.)
- Department of Medicine, Universitat de València, 46010 Valencia, Spain;
| | - Mariola D. Molina
- Department of Mathematics, Universidad de Alicante, 03690 Sant Vicent del Raspeig, Spain;
| | - Juan J. Carrero
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE-171 77 Stockholm, Sweden;
| | - Verónica Escudero
- Department of Nephrology, Hospital Universitari Dr. Peset, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana, 46017 Valencia, Spain; (V.E.); (C.C.-A.); (S.B.); (B.V.); (M.G.-M.); (J.K.); (A.S.-C.)
| | - Javier Torralba
- Department of Nephrology, Hospital General Universitario, 03010 Alicante, Spain;
| | - Cristina Castro-Alonso
- Department of Nephrology, Hospital Universitari Dr. Peset, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana, 46017 Valencia, Spain; (V.E.); (C.C.-A.); (S.B.); (B.V.); (M.G.-M.); (J.K.); (A.S.-C.)
| | - Sandra Beltrán
- Department of Nephrology, Hospital Universitari Dr. Peset, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana, 46017 Valencia, Spain; (V.E.); (C.C.-A.); (S.B.); (B.V.); (M.G.-M.); (J.K.); (A.S.-C.)
| | - Belén Vizcaíno
- Department of Nephrology, Hospital Universitari Dr. Peset, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana, 46017 Valencia, Spain; (V.E.); (C.C.-A.); (S.B.); (B.V.); (M.G.-M.); (J.K.); (A.S.-C.)
- Department of Medicine, Universitat de València, 46010 Valencia, Spain;
| | - Mercedes González-Moya
- Department of Nephrology, Hospital Universitari Dr. Peset, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana, 46017 Valencia, Spain; (V.E.); (C.C.-A.); (S.B.); (B.V.); (M.G.-M.); (J.K.); (A.S.-C.)
- Department of Medicine, Universitat de València, 46010 Valencia, Spain;
| | - Julia Kanter
- Department of Nephrology, Hospital Universitari Dr. Peset, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana, 46017 Valencia, Spain; (V.E.); (C.C.-A.); (S.B.); (B.V.); (M.G.-M.); (J.K.); (A.S.-C.)
| | - Asunción Sancho-Calabuig
- Department of Nephrology, Hospital Universitari Dr. Peset, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana, 46017 Valencia, Spain; (V.E.); (C.C.-A.); (S.B.); (B.V.); (M.G.-M.); (J.K.); (A.S.-C.)
- Department of Medicine, Universitat de València, 46010 Valencia, Spain;
| | - Jordi Bover
- Nephrology Department, University Hospital Germans Trias i Pujol, 08916 Badalona, Spain;
| | - José L. Górriz
- Department of Medicine, Universitat de València, 46010 Valencia, Spain;
- Department of Nephrology, Hospital Clínico Universitario, Fundación para la Investigación del Hospital Clínico de la Comunidad Valenciana, 46010 Valencia, Spain
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Bover J, Massó E, Gifre L, Alfieri C, Soler-Majoral J, Fusaro M, Calabia J, Rodríguez-Pena R, Rodríguez-Chitiva N, López-Báez V, Sánchez-Baya M, da Silva I, Aguilar A, Bustos MC, Rodrigues N, Chávez-Iñiguez JS, Romero-González G, Valdivielso JM, Molina P, Górriz JL. Vitamin D and Chronic Kidney Disease Association with Mineral and Bone Disorder: An Appraisal of Tangled Guidelines. Nutrients 2023; 15:1576. [PMID: 37049415 PMCID: PMC10097233 DOI: 10.3390/nu15071576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Accepted: 03/20/2023] [Indexed: 04/14/2023] Open
Abstract
Chronic kidney disease (CKD) is a highly prevalent condition worldwide in which the kidneys lose many abilities, such as the regulation of vitamin D (VD) metabolism. Moreover, people with CKD are at a higher risk of multifactorial VD deficiency, which has been extensively associated with poor outcomes, including bone disease, cardiovascular disease, and higher mortality. Evidence is abundant in terms of the association of negative outcomes with low levels of VD, but recent studies have lowered previous high expectations regarding the beneficial effects of VD supplementation in the general population. Although controversies still exist, the diagnosis and treatment of VD have not been excluded from nephrology guidelines, and much data still supports VD supplementation in CKD patients. In this narrative review, we briefly summarize evolving controversies and useful clinical approaches, underscoring that the adverse effects of VD derivatives must be balanced against the need for effective prevention of progressive and severe secondary hyperparathyroidism. Guidelines vary, but there seems to be general agreement that VD deficiency should be avoided in CKD patients, and it is likely that one should not wait until severe SHPT is present before cautiously starting VD derivatives. Furthermore, it is emphasized that the goal should not be the complete normalization of parathyroid hormone (PTH) levels. New developments may help us to better define optimal VD and PTH at different CKD stages, but large trials are still needed to confirm that VD and precise control of these and other CKD-MBD biomarkers are unequivocally related to improved hard outcomes in this population.
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Affiliation(s)
- Jordi Bover
- Department of Nephrology, University Hospital Germans Trias i Pujol, 08916 Badalona, Spain
- REMAR-IGTP Group, Research Institute Germans Trias i Pujol, Can Ruti Campus, 08916 Badalona, Spain
| | - Elisabet Massó
- Department of Nephrology, University Hospital Germans Trias i Pujol, 08916 Badalona, Spain
- REMAR-IGTP Group, Research Institute Germans Trias i Pujol, Can Ruti Campus, 08916 Badalona, Spain
| | - Laia Gifre
- Rheumatology Service, University Hospital Germans Trias i Pujol, 08916 Badalona, Spain
| | - 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
| | - Jordi Soler-Majoral
- Department of Nephrology, University Hospital Germans Trias i Pujol, 08916 Badalona, Spain
- REMAR-IGTP Group, Research Institute Germans Trias i Pujol, Can Ruti Campus, 08916 Badalona, Spain
| | - Maria Fusaro
- National Research Council (CNR), 56124 Pisa, Italy
- Department of Medicine, University of Padua, 35128 Padova, Italy
| | - Jordi Calabia
- Department of Nephrology, University Hospital Josep Trueta, 17007 Girona, Spain
| | - Rosely Rodríguez-Pena
- Department of Nephrology, University Hospital Germans Trias i Pujol, 08916 Badalona, Spain
- REMAR-IGTP Group, Research Institute Germans Trias i Pujol, Can Ruti Campus, 08916 Badalona, Spain
| | - Néstor Rodríguez-Chitiva
- Department of Nephrology, University Hospital Germans Trias i Pujol, 08916 Badalona, Spain
- REMAR-IGTP Group, Research Institute Germans Trias i Pujol, Can Ruti Campus, 08916 Badalona, Spain
| | - Víctor López-Báez
- Department of Nephrology, University Hospital Germans Trias i Pujol, 08916 Badalona, Spain
- REMAR-IGTP Group, Research Institute Germans Trias i Pujol, Can Ruti Campus, 08916 Badalona, Spain
| | - Maya Sánchez-Baya
- Department of Nephrology, University Hospital Germans Trias i Pujol, 08916 Badalona, Spain
- REMAR-IGTP Group, Research Institute Germans Trias i Pujol, Can Ruti Campus, 08916 Badalona, Spain
| | - Iara da Silva
- Department of Nephrology, University Hospital Germans Trias i Pujol, 08916 Badalona, Spain
- REMAR-IGTP Group, Research Institute Germans Trias i Pujol, Can Ruti Campus, 08916 Badalona, Spain
| | - Armando Aguilar
- Department of Nephrology, Instituto Mexicano del Seguro Social, Hospital General de Zona No. 2, Tuxtla Gutiérrez 29000, Mexico
| | - Misael C. Bustos
- Department of Nephrology, Pontificia Catholic University of Chile, Santiago 8331150, Chile
| | - Natacha Rodrigues
- Division of Nephrology and Renal Transplantation, Department of Medicine, Centro Hospitalar Universitário Lisboa Norte, EPE, 1649-028 Lisboa, Portugal
| | - Jonathan S. Chávez-Iñiguez
- Department of Nephrology, Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara 44280, Mexico
- Centro Universitario de Ciencias de la Salud CUCS, Guadalajara University, Guadalajara 44340, Mexico
| | - Gregorio Romero-González
- Department of Nephrology, University Hospital Germans Trias i Pujol, 08916 Badalona, Spain
- REMAR-IGTP Group, Research Institute Germans Trias i Pujol, Can Ruti Campus, 08916 Badalona, Spain
| | - José Manuel Valdivielso
- Grupo de Investigación Traslacional Vascular y Renal, Instituto de Investigación Biomédica IRBlleida, 25198 Lleida, Spain
| | - Pablo Molina
- Department of Nephrology, Hospital Universitario Dr Peset, Universitat de València Fisabio, 46017 Valencia, Spain
| | - José L. Górriz
- Department of Nephrology, University Hospital Clínico, INCLIVA, Valencia University, 46010 Valencia, Spain
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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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9
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Martinelli RP, Rayego-Mateos S, Alique M, Márquez-Expósito L, Tejedor-Santamaria L, Ortiz A, González-Parra E, Ruiz-Ortega M. Vitamin D, Cellular Senescence and Chronic Kidney Diseases: What Is Missing in the Equation? Nutrients 2023; 15:1349. [PMID: 36986078 PMCID: PMC10056834 DOI: 10.3390/nu15061349] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Revised: 03/07/2023] [Accepted: 03/09/2023] [Indexed: 03/12/2023] Open
Abstract
As life expectancy increases in many countries, the prevalence of age-related diseases also rises. Among these conditions, chronic kidney disease is predicted to become the second cause of death in some countries before the end of the century. An important problem with kidney diseases is the lack of biomarkers to detect early damage or to predict the progression to renal failure. In addition, current treatments only retard kidney disease progression, and better tools are needed. Preclinical research has shown the involvement of the activation of cellular senescence-related mechanisms in natural aging and kidney injury. Intensive research is searching for novel treatments for kidney diseases as well as for anti-aging therapies. In this sense, many experimental shreds of evidence support that treatment with vitamin D or its analogs can exert pleiotropic protective effects in kidney injury. Moreover, vitamin D deficiency has been described in patients with kidney diseases. Here, we review recent evidence about the relationship between vitamin D and kidney diseases, explaining the underlying mechanisms of the effect of vitamin D actions, with particular attention to the modulation of cellular senescence mechanisms.
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Affiliation(s)
- Romina P. Martinelli
- Cellular Biology in Renal Diseases Laboratory, IIS-Fundación Jiménez Díaz-Universidad Autónoma, 28040 Madrid, Spain
| | - Sandra Rayego-Mateos
- Cellular Biology in Renal Diseases Laboratory, IIS-Fundación Jiménez Díaz-Universidad Autónoma, 28040 Madrid, Spain
- Ricors2040, 28029 Madrid, Spain
| | - Matilde Alique
- Ricors2040, 28029 Madrid, Spain
- Departamento de Biología de Sistemas, Universidad de Alcalá, Alcalá de Henares, 28871 Madrid, Spain
- Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain
| | - Laura Márquez-Expósito
- Cellular Biology in Renal Diseases Laboratory, IIS-Fundación Jiménez Díaz-Universidad Autónoma, 28040 Madrid, Spain
- Ricors2040, 28029 Madrid, Spain
| | - Lucia Tejedor-Santamaria
- Cellular Biology in Renal Diseases Laboratory, IIS-Fundación Jiménez Díaz-Universidad Autónoma, 28040 Madrid, Spain
- Ricors2040, 28029 Madrid, Spain
| | - Alberto Ortiz
- Ricors2040, 28029 Madrid, Spain
- Department of Nephrology and Hypertension, IIS-Fundación Jiménez Díaz-Universidad Autónoma Madrid, 28040 Madrid, Spain
| | - Emilio González-Parra
- Ricors2040, 28029 Madrid, Spain
- Department of Nephrology and Hypertension, IIS-Fundación Jiménez Díaz-Universidad Autónoma Madrid, 28040 Madrid, Spain
| | - Marta Ruiz-Ortega
- Cellular Biology in Renal Diseases Laboratory, IIS-Fundación Jiménez Díaz-Universidad Autónoma, 28040 Madrid, Spain
- Ricors2040, 28029 Madrid, Spain
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10
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Karalliedde J, Fountoulakis N, Corcillo A, Maltese G, Flaquer M, Stathi D, Mangelis A, Panagiotou A, Ayis S, Thomas S, Gnudi L. Effect of calcitriol treatment on arterial stiffness in people with type 2 diabetes and stage 3 chronic kidney disease. Br J Clin Pharmacol 2023; 89:279-289. [PMID: 35942813 PMCID: PMC10087300 DOI: 10.1111/bcp.15484] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 08/01/2022] [Indexed: 11/28/2022] Open
Abstract
AIMS Active vitamin D deficiency is associated with increased aortic-pulse wave velocity (Ao-PWV) in people with type 2 diabetes (T2DM) and chronic kidney disease (CKD). There are no randomised controlled trials investigating the effect of active vitamin D treatment on Ao-PWV in people with T2DM and CKD. METHODS A 48-week duration single-centre randomised double-blind parallel-group trial examined the impact of oral 1,25 dihydroxyvitamin D (calcitriol 0.25 mcg OD) as compared to placebo on a primary endpoint of Ao-PWV. People with T2DM and stable stage 3 CKD with intact parathyroid hormone (iPTH) level >30 pg/mL were eligible. RESULTS In total, 127 (70% male) people were randomised (calcitriol n = 64 or placebo n = 63). There was no change in Ao-PWV observed, mean ± standard deviation (SD), in the calcitriol group of 11.79 (±2.5) to 12.08 (3.0) m/s as compared to 10.90 (±2.4) to 11.39 (±2.6) m/s with placebo. The between-treatment group adjusted mean (95% confidence interval [(CI]] change was 0.23 (-0.58 to 1.05) m/s, P = .57. No effect of calcitriol was observed on central arterial pressures, albuminuria, serum calcium or phosphate levels. However, iPTH fell with calcitriol treatment (mean [95% CI] between-group difference of -27.8 (-42.3 to -13.2) pg/mL, P < .001. CONCLUSION In T2DM and stage 3 CKD, calcitriol as compared to placebo does not improve Ao-PWV or other markers of arterial stiffness. Our study does not provide evidence for the use of active vitamin D for improving arterial stiffness in T2DM with stage 3 CKD.
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Affiliation(s)
- Janaka Karalliedde
- School of Cardiovascular and Metabolic Medicine and Sciences, King's College London, London, UK
| | - Nikolaos Fountoulakis
- School of Cardiovascular and Metabolic Medicine and Sciences, King's College London, London, UK
| | - Antonella Corcillo
- School of Cardiovascular and Metabolic Medicine and Sciences, King's College London, London, UK
| | - Giuseppe Maltese
- School of Cardiovascular and Metabolic Medicine and Sciences, King's College London, London, UK
| | - Maria Flaquer
- School of Cardiovascular and Metabolic Medicine and Sciences, King's College London, London, UK
| | - Dimitra Stathi
- School of Cardiovascular and Metabolic Medicine and Sciences, King's College London, London, UK
| | - Anastasios Mangelis
- School of Population Health & Environmental Sciences, King's College London, London, UK
| | - Angeliki Panagiotou
- School of Cardiovascular and Metabolic Medicine and Sciences, King's College London, London, UK
| | - Salma Ayis
- School of Population Health & Environmental Sciences, King's College London, London, UK
| | - Stephen Thomas
- School of Cardiovascular and Metabolic Medicine and Sciences, King's College London, London, UK
| | - Luigi Gnudi
- School of Cardiovascular and Metabolic Medicine and Sciences, King's College London, London, UK
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11
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Matias PJ, Laranjinha I, Ávila G, Azevedo A, Jorge C, Ferreira C, Aires I, Amaral T, Gil C, Ferreira A. Long-term cholecalciferol supplementation in hemodialysis patients: Effects on mineral metabolism, inflammation, and cardiac parameters. Semin Dial 2023; 36:29-36. [PMID: 35262225 DOI: 10.1111/sdi.13066] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Accepted: 02/13/2022] [Indexed: 02/01/2023]
Abstract
BACKGROUND Low levels of 25-hydroxyvitamin D [25(OH)D] are frequent in chronic kidney disease and are associated with adverse outcomes. The aim of this 5-year prospective study was to evaluate the effects of cholecalciferol supplementation on mineral metabolism, inflammation and cardiac parameters in hemodialysis (HD) patients. METHODS The study included 97 patients. Cholecalciferol was given after HD according to 25(OH)D baseline levels measured twice (end of winter and of summer). The 25(OH)D levels, circulating bone metabolism, inflammation parameters, brain natriuretic peptide (BNP), pulse pressure (PP), and left ventricular mass index (LVMI) were evaluated before and after supplementation. RESULTS There was a significant increase in 25(OH)D levels after supplementation (p < 0.001); however, serum calcium (p = 0.02), phosphorus (p = 0.018), and iPTH (p = 0.03) were decreased. Magnesium levels increased during the study (p = 0.03). A reduction in the number of patients under active vitamin D (p < 0.001) and in the dose and number of patients treated with darbepoetin (p = 0.02) was observed. Serum albumin increased (p < 0.001), and C-reactive protein decreased (p = 0.01). BNP (p < 0.001), PP (p = 0.007), and LVMI (p = 0.02) were significantly reduced after supplementation. CONCLUSIONS Long-term cholecalciferol supplementation allowed correction of 25(OH)D deficiency, improved mineral metabolism with less use of active vitamin D, attenuated inflammation, reduced the dose of the erythropoiesis-stimulating agent, and improved cardiac dysfunction.
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Affiliation(s)
- Patrícia João Matias
- Dialysis Unit, Nephrocare Vila Franca de Xira, Vila Franca de Xira, Portugal.,Dialysis Unit, Dialverca, Forte da Casa, Portugal.,NIDAN, Lisbon, Portugal.,Faculdade de Ciências Médicas, NOVA Medical School, Lisboa, Portugal
| | - Ivo Laranjinha
- Dialysis Unit, Nephrocare Vila Franca de Xira, Vila Franca de Xira, Portugal.,Dialysis Unit, Dialverca, Forte da Casa, Portugal.,NIDAN, Lisbon, Portugal
| | - Gonçalo Ávila
- Dialysis Unit, Nephrocare Vila Franca de Xira, Vila Franca de Xira, Portugal.,Dialysis Unit, Dialverca, Forte da Casa, Portugal.,NIDAN, Lisbon, Portugal
| | - Ana Azevedo
- Dialysis Unit, Nephrocare Vila Franca de Xira, Vila Franca de Xira, Portugal.,Dialysis Unit, Dialverca, Forte da Casa, Portugal.,NIDAN, Lisbon, Portugal
| | - Cristina Jorge
- Dialysis Unit, Nephrocare Vila Franca de Xira, Vila Franca de Xira, Portugal.,Dialysis Unit, Dialverca, Forte da Casa, Portugal.,NIDAN, Lisbon, Portugal
| | - Carina Ferreira
- Dialysis Unit, Nephrocare Vila Franca de Xira, Vila Franca de Xira, Portugal.,Dialysis Unit, Dialverca, Forte da Casa, Portugal.,NIDAN, Lisbon, Portugal.,Faculdade de Ciências Médicas, NOVA Medical School, Lisboa, Portugal
| | - Inês Aires
- Dialysis Unit, Nephrocare Vila Franca de Xira, Vila Franca de Xira, Portugal.,Dialysis Unit, Dialverca, Forte da Casa, Portugal.,NIDAN, Lisbon, Portugal.,Faculdade de Ciências Médicas, NOVA Medical School, Lisboa, Portugal
| | - Tiago Amaral
- Dialysis Unit, Nephrocare Vila Franca de Xira, Vila Franca de Xira, Portugal.,Dialysis Unit, Dialverca, Forte da Casa, Portugal.,NIDAN, Lisbon, Portugal
| | - Célia Gil
- Dialysis Unit, Nephrocare Vila Franca de Xira, Vila Franca de Xira, Portugal.,Dialysis Unit, Dialverca, Forte da Casa, Portugal.,NIDAN, Lisbon, Portugal
| | - Aníbal Ferreira
- Dialysis Unit, Nephrocare Vila Franca de Xira, Vila Franca de Xira, Portugal.,Dialysis Unit, Dialverca, Forte da Casa, Portugal.,NIDAN, Lisbon, Portugal.,Faculdade de Ciências Médicas, NOVA Medical School, Lisboa, Portugal
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12
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Limonte CP, Zelnick LR, Hoofnagle AN, Thadhani R, Melamed ML, Mora S, Cook NR, Luttmann-Gibson H, Sesso HD, Lee IM, Buring JE, Manson JE, de Boer IH. Effects of Vitamin D 3 Supplementation on Cardiovascular and Cancer Outcomes by eGFR in VITAL. KIDNEY360 2022; 3:2095-2105. [PMID: 36591342 PMCID: PMC9802543 DOI: 10.34067/kid.0006472022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Accepted: 10/19/2022] [Indexed: 04/26/2023]
Abstract
Background Reduced 25-hydroxyvitamin D (25[OH]D) metabolism and secondary hyperparathyroidism are common with lower estimated glomerular filtration rate (eGFR) and may contribute to cardiovascular disease and cancer risk. Methods We assessed for heterogeneity by baseline eGFR of the effects of vitamin D3 on cardiovascular and cancer outcomes in the Vitamin D and Omega-3 Trial (VITAL). Participants were randomized to 2000 IU vitamin D3 and/or 1 g Ω-3 fatty acids daily using a placebo-controlled, two-by-two factorial design (5.3 years follow-up). Primary study end points were incident major cardiovascular events and invasive cancer. Changes in serum 25(OH)D and parathyroid hormone (PTH) were examined. Results Baseline eGFR was available for 15,917 participants. Participants' mean age was 68 years, and 51% were women. Vitamin D3 resulted in higher serum 25(OH)D compared with placebo (difference in change 12.5 ng/ml; 95% CI, 12 to 13.1 ng/ml), without heterogeneity by eGFR (P interaction, continuous eGFR=0.2). Difference in change in PTH between vitamin D3 and placebo was larger with lower eGFR (P interaction=0.05): -6.9 (95% CI, -10.5 to -3.4), -5.8 (95% CI, -8.3 to -3.4), -4 (95% CI, -5.9 to -2.2), and -3.8 (95% CI, -5.6 to -2) pg/ml for eGFR <60, 60-74, 75-89, and ≥90 ml/min per 1.73 m2, respectively. Effects of vitamin D3 supplementation on cardiovascular events (P interaction=0.61) and cancer (P interaction=0.89) did not differ by eGFR: HR=1.14 (95% CI, 0.73 to 1.79), HR=1.06 (95% CI, 0.75 to 1.5), HR=0.92 (95% CI, 0.67 to 1.25), and HR=0.92 (95% CI, 0.66 to 1.27) across eGFR categories for cardiovascular events and HR=1.63 (95% CI, 1.03 to 2.58), HR=0.85 (95% CI, 0.64 to 1.11), HR=0.84 (95% CI, 0.68 to 1.03), and 1.11 (95% CI, 0.92 to 1.35) for cancer, respectively. Conclusions We observed no significant heterogeneity by baseline eGFR in the effects of vitamin D3 supplementation versus placebo on cardiovascular or cancer outcomes, despite effects on 25(OH)D and PTH concentrations.
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Affiliation(s)
- Christine P Limonte
- Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington
- Kidney Research Institute, University of Washington, Seattle, Washington
| | - Leila R Zelnick
- Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington
- Kidney Research Institute, University of Washington, Seattle, Washington
| | - Andrew N Hoofnagle
- Kidney Research Institute, University of Washington, Seattle, Washington
- Department of Laboratory Medicine, University of Washington, Seattle, Washington
| | - Ravi Thadhani
- Office of the Chief Academic Officer, Mass General Brigham, Boston, Massachusetts
| | - Michal L Melamed
- Division of Nephrology, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York
| | - Samia Mora
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts
- Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Nancy R Cook
- Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Heike Luttmann-Gibson
- Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Howard D Sesso
- Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - I-Min Lee
- Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Julie E Buring
- Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - JoAnn E Manson
- Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Ian H de Boer
- Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington
- Kidney Research Institute, University of Washington, Seattle, Washington
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13
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Rios P, Silvariño R, Sola L, Ferreiro A, Lamadrid V, Fajardo L, Gadola L. Mineral and bone disorder and longterm survival in a chronic kidney disease grade 3b-4cohort. Ren Fail 2022; 44:1356-1367. [PMID: 35946486 PMCID: PMC9373789 DOI: 10.1080/0886022x.2022.2107543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Revised: 07/13/2022] [Accepted: 07/24/2022] [Indexed: 11/13/2022] Open
Abstract
Mineral and bone disorder biomarkers 'normal ranges' are controversial. The aim of the study was to evaluate the association between serum calcium (Ca), phosphate (P), intact parathyroid hormone (iPTH), and 25(OH) vitamin D levels and mortality risk, in a chronic kidney disease (CKD) grade (G) 3b-4 cohort. The Uruguayan National Renal Healthcare Program (NRHP-UY) CKD patients' cohort, included between 1 October 2004 and 1 March 2020 and followed-up until 1 March 2021, was analyzed with the Ethics Committee approval. A total of 6473 patients were analyzed: 56% men, median age 73 (65-79) years, 55% on CKD G3b. At the end of the follow-up, 2459 (37.7%) patients had died (6.4/100 patient-year). There were iPTH data on 2013 patients (younger, with lower estimated glomerular filtration rate (eGFR) and lesser comorbidities). By bivariate Cox analysis the lowest death risk was observed with mean Ca between 9.01 and 10.25 mg/dl, P between 2.76 and 4.0 mg/dl, iPTH ≤ 105 pg/ml, and 25(OH) vitamin D >10 ng/ml. The multivariate Cox regression mortality risk adjusted to age, sex, CKD etiology, diabetes, smoking, cardiovascular comorbidity, blood pressure, proteinuria, eGFR, renin-angiotensin system blockers and vitamin D treatments, serum Ca, P, iPTH, and 25(OH) vitamin D (n = 964) showed that a higher mortality risk was associated with p > 4.00 mg/dl (HR 1.668, CI 95%: 1.201-2.317), iPTH >105 pg/ml (HR 1.386, CI 95%: 1.012-1.989), and 25(OH) vitamin D ≤ 10 ng/ml (HR 1.958, CI 95%: 1.238-3.098) and a lower mortality risk with 1,25(OH)2 vitamin D treatment (HR 0.639, CI 95%: 0.451-0.906). These data may contribute to the precise G3b-4 CKD-MBD biomarkers levels definition.
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Affiliation(s)
- Pablo Rios
- Comisión Asesora Programa de Salud Renal, Fondo Nacional de Recursos, Montevideo, Uruguay
| | - Ricardo Silvariño
- Comisión Asesora Programa de Salud Renal, Fondo Nacional de Recursos, Montevideo, Uruguay
- Facultad de Medicina, Universidad de la República, Montevideo, Uruguay
| | - Laura Sola
- Comisión Asesora Programa de Salud Renal, Fondo Nacional de Recursos, Montevideo, Uruguay
| | - Alejandro Ferreiro
- Comisión Asesora Programa de Salud Renal, Fondo Nacional de Recursos, Montevideo, Uruguay
- Facultad de Medicina, Universidad de la República, Montevideo, Uruguay
| | - Verónica Lamadrid
- Comisión Asesora Programa de Salud Renal, Fondo Nacional de Recursos, Montevideo, Uruguay
| | - Laura Fajardo
- Sociedad Uruguaya de Nefrología, Montevideo, Uruguay
| | - Liliana Gadola
- Comisión Asesora Programa de Salud Renal, Fondo Nacional de Recursos, Montevideo, Uruguay
- Facultad de Medicina, Universidad de la República, Montevideo, Uruguay
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14
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Zhang H, Jiang Y, Shi N, Lu YQ. Serum vitamin D levels and acute kidney injury: a systemic review and meta-analysis. Sci Rep 2022; 12:20365. [PMID: 36437252 PMCID: PMC9701671 DOI: 10.1038/s41598-022-24560-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 11/16/2022] [Indexed: 11/28/2022] Open
Abstract
Numerous researches have evaluated the prevalence and clinical outcome of vitamin D deficiency in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). But the quantitative vitamin D status in acute kidney injury (AKI) patients and its relationship with prognosis remains controversial. We conducted this systemic review and meta-analysis to assess the quantitative difference of vitamin D status, including serum 25(OH) D and 1,25(OH)2D levels, between AKI patients and non-AKI controls, and further explore whether vitamin D status can be clearly correlated with the mortality of AKI. Major databases, including PubMed, Web of Science and EBSCO, were searched until 1st September 2021. All published observational studies related to vitamin D and AKI According to predefined inclusion and exclusion criteria were extracted. Meta-analyses were performed using Review Manager 5.3.5. Four studies including five cohorts were included with a total of 413 patients. The serum 25(OH)D levels showed no statistically significant difference in AKI patients and non-AKI controls. On the other hand, the serum 1,25(OH)2D levels were significant lower in AKI patients than in non-AKI controls (MD = - 17.79, 95% CI = - 32.73 to - 2.85, P = 0.02). As for the relationship between serum vitamin D status and AKI patients' mortality, we were unable to give a consistent conclusion based on current limited and conflict study results. Our meta-analysis suggested that serum 1,25(OH)2D levels, rather than 25(OH)D, is significantly lower in AKI patients. The relationship between vitamin D status and clinical outcome of AKI remains controversial based on current evidence. Future comprehensive studies are required to confirm these relations and to elucidate potential mechanisms.
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Affiliation(s)
- Huanran Zhang
- Department of Emergency Medicine, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, 310003, People's Republic of China
- Key Laboratory of Diagnosis and Treatment of Aging and Physic-Chemical Injury Diseases of Zhejiang Province, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Yan Jiang
- Kidney Disease Center, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, People's Republic of China
| | - Nan Shi
- Kidney Disease Center, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, People's Republic of China
| | - Yuan-Qiang Lu
- Department of Emergency Medicine, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, 310003, People's Republic of China.
- Key Laboratory of Diagnosis and Treatment of Aging and Physic-Chemical Injury Diseases of Zhejiang Province, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.
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15
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Ike T, Doi S, Nakashima A, Sasaki K, Ishiuchi N, Asano T, Masaki T. The hypoxia-inducible factor-α prolyl hydroxylase inhibitor FG4592 ameliorates renal fibrosis by inducing the H3K9 demethylase JMJD1A. Am J Physiol Renal Physiol 2022; 323:F539-F552. [PMID: 36074918 DOI: 10.1152/ajprenal.00083.2022] [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: 12/14/2022] Open
Abstract
The transcription factors hypoxia-inducible factor-1α and -2α (HIF-1α/2α) are the major regulators of the cellular response to hypoxia and play a key role in renal fibrosis associated with acute and chronic kidney disease. Jumonji domain-containing 1a (JMJD1A), a histone H3 lysine 9 (H3K9) demethylase, is reported to be an important target gene of HIF-α. However, whether JMJD1A and H3K9 methylation status play a role in renal fibrosis is unclear. Here, we investigated the involvement of HIF-α, JMJD1A, and monomethylated/dimethylated H3K9 (H3K9me1/H3K9me2) levels in unilateral ureteral obstruction (UUO)-induced renal fibrosis in mice. Intraperitoneal administration of FG4592, an inhibitor of HIF-α prolyl hydroxylase, which controls HIF-α protein stability, significantly attenuated renal fibrosis on days 3 and 7 following UUO. FG4592 concomitantly increased JMJD1A expression, decreased H3K9me1/me2 levels, reduced profibrotic gene expression, and increased erythropoietin expression in renal tissues of UUO mice. The beneficial effects of FG4592 on renal fibrosis were inhibited by the administration of JMJD1A-specific siRNA to mice immediately following UUO. Incubation of normal rat kidney-49F and/or -52E cells with transforming growth factor-β1 (TGF-β1) in vitro resulted in upregulated expression of α-smooth muscle actin and H3K9me1/me2, and these effects were inhibited by cotreatment with FG4592. In contrast, FG4592 treatment further enhanced the TGF-β1-stimulated upregulation of JMJD1A but had no effect on TGF-β1-stimulated expression of the H3K9 methyltransferase euchromatic histone-lysine N-methyltransferase 2. Collectively, these findings establish a crucial role for the HIF-α1/2-JMJD1A-H3K9me1/me2 regulatory axis in the therapeutic effect of FG4592 in renal fibrosis.NEW & NOTEWORTHY Using a mouse model of renal fibrosis and transforming growth factor-β1-stimulated rat cell lines, we show that treatment with FG4592, an inhibitor of hypoxia-inducible factor-1α and -2α (HIF-1α/2α) prolyl hydroxylase decreases renal fibrosis and concomitantly reduces methylated lysine 9 of histone H3 (H3K9) levels via upregulation of Jumonji domain-containing 1a (JMJD1A). The results identify a novel role for the HIF-1α/2α-JMJD1A-H3K9 regulatory axis in suppressing renal fibrosis.
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Affiliation(s)
- Takeshi Ike
- Department of Nephrology, Hiroshima University Hospital, Hiroshima, Japan
| | - Shigehiro Doi
- Department of Nephrology, Hiroshima University Hospital, Hiroshima, Japan
| | - Ayumu Nakashima
- Department of Nephrology, Hiroshima University Hospital, Hiroshima, Japan.,Department of Stem Cell Biology and Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kensuke Sasaki
- Department of Nephrology, Hiroshima University Hospital, Hiroshima, Japan
| | - Naoki Ishiuchi
- Department of Nephrology, Hiroshima University Hospital, Hiroshima, Japan
| | - Tomoichiro Asano
- Department of Medical Science, Graduate School of Medicine, Hiroshima University, Hiroshima, Japan
| | - Takao Masaki
- Department of Nephrology, Hiroshima University Hospital, Hiroshima, Japan
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Trisiana DY, Yani FF, Amelin F, Pabuti A. Calcitriol levels and the stage of chronic kidney disease in children. PAEDIATRICA INDONESIANA 2022. [DOI: 10.14238/pi62.5.2022.318-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Background Kidney damage in chronic kidney disease (CKD) disrupts the 1?-hydroxylase enzyme, preventing the conversion of vitamin D into the active form of calcitriol. To our knowledge, no previous studies have assessed calcitriol levels in children with CKD. Decreased vitamin D levels may occur at an early stage of the disease, so it is important to evaluate calcitriol levels in children with early stage CKD.
Objective To assess calcitriol levels in children with CKD according to disease stage and other characteristics.
Methods This cross-sectional study was conducted on 43 pediatric CKD patients at Dr. M Djamil Hospital, Padang, Indonesia. We recorded patient characteristics and performed laboratory tests, including routine hematology, blood urea nitrogen (BUN), creatinine, uric acid, electrolytes, calcium, and calcitriol levels. Based on estimated glomerular filtration rate (GFR), patients were grouped into either early-stage (stages I and II), or advanced-stage (stages III to V) CKD. Univariate and multivariate analyses were conducted to determine the association between calcitriol levels with disease stage and other characteristics.
Results The overall mean calcitriol level of our subjects was 108.77 (SD 10.79) pmol/L. Mean levels at each CKD stage from I to V were 164.28 (SD 160.90), 94.14 (SD 50.63), 72.16 (SD 13.18), 62.92 (SD 4.87), and 67.51 (SD 4.87) pmol/L, respectively. Calcitriol levels did not differ significantly by CKD stage (P=0.114) when each stage from I to V was considered separately. There was no significant difference in calcitriol levels by growth characteristics (P=0.944), etiology (P=0.311), or anemic status (P=0.104). However, low calcitriol levels were found in all subjects with advanced stage CKD, compared to 63.6% subjects with early stage CKD (P=0.004). Mean calcitriol levels were significantly lower in CKD stage IV (P=0.049) and stage V (P=0.027) compared to stage I.
Conclusions The decrease in calcitriol level occurs at an early stage in CKD. Calcitriol levels are significantly lower in advanced stage than in early stage CKD.
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Liu D, Meng X, Tian Q, Cao W, Fan X, Wu L, Song M, Meng Q, Wang W, Wang Y. Vitamin D and Multiple Health Outcomes: An Umbrella Review of Observational Studies, Randomized Controlled Trials, and Mendelian Randomization Studies. Adv Nutr 2022; 13:1044-1062. [PMID: 34999745 PMCID: PMC9340982 DOI: 10.1093/advances/nmab142] [Citation(s) in RCA: 50] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Revised: 12/29/2020] [Accepted: 11/19/2021] [Indexed: 12/18/2022] Open
Abstract
Observational studies, randomized controlled trials (RCTs), and Mendelian randomization (MR) studies have yielded inconsistent results on the associations of vitamin D concentrations with multiple health outcomes. In the present umbrella review we aimed to evaluate the effects of low vitamin D concentrations and vitamin D supplementation on multiple health outcomes. We summarized current evidence obtained from meta-analyses of observational studies that examined associations between vitamin D concentrations and multiple health outcomes, meta-analyses of RCTs that investigated the effect of vitamin D supplementation on multiple health outcomes, and MR studies that explored the causal associations of vitamin D concentrations with various diseases (international prospective register of systematic reviews PROSPERO registration number CRD42018091434). A total of 296 meta-analyses of observational studies comprising 111 unique outcomes, 139 meta-analyses of RCTs comprising 46 unique outcomes, and 73 MR studies comprising 43 unique outcomes were included in the present umbrella review. Twenty-eight disease outcomes were identified by both meta-analyses of observational studies and MR studies. Seventeen of these reported disease outcomes had consistent results, demonstrating that lower concentrations of vitamin D were associated with a higher risk for all-cause mortality, Alzheimer's disease, hypertension, schizophrenia, and type 2 diabetes. The combinations of consistent evidence obtained by meta-analyses of observational studies and MR studies together with meta-analyses of RCTs showed that vitamin D supplementation was associated with a decreased risk for all-cause mortality but not associated with the risk for Alzheimer's disease, hypertension, schizophrenia, or type 2 diabetes. The results indicated that vitamin D supplementation is a promising strategy with long-term preventive effects on multiple chronic diseases and thus has the potential to decrease all-cause mortality. However, the current vitamin D supplementation strategy might not be an efficient intervention approach for these diseases, suggesting that new strategies are highly needed to improve the intervention outcomes.
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Affiliation(s)
- Di Liu
- Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China
- Centre for Biomedical Information Technology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China
| | - Xiaoni Meng
- Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China
| | - Qiuyue Tian
- Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China
| | - Weijie Cao
- Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China
| | - Xin Fan
- School of Basic Medical Sciences, Capital Medical University, Beijing, China
| | - Lijuan Wu
- Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China
| | - Manshu Song
- Centre for Precision Health, School of Medical and Health Sciences, Edith Cowan University, Perth, WA, Australia
| | - Qun Meng
- Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China
| | - Wei Wang
- Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China
- Centre for Precision Health, School of Medical and Health Sciences, Edith Cowan University, Perth, WA, Australia
- School of Public Health, Shandong First Medical University and Shandong Academy of Medical Science, Tai'an, Shandong, China
| | - Youxin Wang
- Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China
- Centre for Precision Health, School of Medical and Health Sciences, Edith Cowan University, Perth, WA, Australia
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Khelifi N, Desbiens L, Sidibé A, Mac‐Way F. Vitamin D Analogues and Fracture Risk in Chronic Kidney Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. JBMR Plus 2022; 6:e10611. [PMID: 35434454 PMCID: PMC9009117 DOI: 10.1002/jbm4.10611] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 01/25/2022] [Indexed: 11/15/2022] Open
Abstract
Vitamin D receptor agonists (VDRAs) are commonly prescribed in chronic kidney disease (CKD). However, their protective effects on bone remain controversial. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of VDRAs on fracture risk and bone mineral density (BMD) in adult patients with CKD. We searched MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov, and the WHO's International Clinical Trials Registry Platform databases from inception to June 19, 2021. We included RCTs comparing VDRAs, to placebo or another medication, in adults with CKD requiring or not dialysis. Conference abstracts and trials involving kidney transplant recipients and/or comparing VDRAs to antiresorptive or anabolic bone therapy were excluded. Primary outcome was fracture at any anatomical site. Secondary outcomes were BMD at femoral neck, lumbar spine, and/or total hip. Prespecified subgroup analyses were conducted according to baseline demographics, overall risk of bias, and follow-up time. From 6868 references retrieved, eight RCTs were eligible: five reported fracture, two reported BMD, and one reported both outcomes. As comparator, one study used no VDRAs, one used nutritional intervention and no medication, and six used placebo. In meta-analysis, VDRAs were not associated with a significant reduction in total fractures in overall (risk ratio = 0.79, 95% confidence interval 0.38-1.65, I2 = 0%, six trials, 1507 participants, 27 fractures) or in prespecified subgroup analyses. Three trials reported BMD at different sites and with different BMD measurements; thus, a meta-analysis could not be performed. Two RCTs were at high risk of bias, notably because of deviations from the intended interventions. As limitation, we have to mention the low total number of fractures included in our meta-analysis. In conclusion, current evidence from RCTs is insufficient to associate VDRAs with bone protection in CKD. Further large and long-term studies specifically designed to evaluate the efficacy of VDRAs on bone outcomes are thus required. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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Affiliation(s)
- Nada Khelifi
- CHU de Québec Research Center, Division of NephrologyEndocrinology and Nephrology AxisQuebec CityCanada
- Faculty and Department of MedicineUniversité LavalQuebec CityCanada
| | - Louis‐Charles Desbiens
- CHU de Québec Research Center, Division of NephrologyEndocrinology and Nephrology AxisQuebec CityCanada
- Faculty and Department of MedicineUniversité LavalQuebec CityCanada
| | - Aboubacar Sidibé
- CHU de Québec Research Center, Division of NephrologyEndocrinology and Nephrology AxisQuebec CityCanada
- Faculty of Medicine, Department of Social and Preventive MedicineUniversité LavalQuebec CityCanada
| | - Fabrice Mac‐Way
- CHU de Québec Research Center, Division of NephrologyEndocrinology and Nephrology AxisQuebec CityCanada
- Faculty and Department of MedicineUniversité LavalQuebec CityCanada
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KARTAL BAYKAN E, YILDIRIMER Y, DURMAZATAR İ. Tip 2 diyabetli bireylerde serum vitamin D düzeyleri ile mikroalbüminüri arasındaki ilişkinin değerlendirilmesi. EGE TIP DERGISI 2022. [DOI: 10.19161/etd.1086114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
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Koshi-Ito E, Inaguma D, Koide S, Takahashi K, Hayashi H, Tsuboi N, Hasegawa M, Maruyama S, Yuzawa Y. Relationship between selection of dosage forms of vitamin D receptor activators and short-term survival of patients on hemodialysis. Ren Fail 2021; 43:1528-1538. [PMID: 34787531 PMCID: PMC8604548 DOI: 10.1080/0886022x.2021.1995423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Revised: 10/08/2021] [Accepted: 10/12/2021] [Indexed: 10/30/2022] Open
Abstract
BACKGROUND The benefits of vitamin D receptor activators (VDRAs) for patients with chronic kidney disease are well recognized. However, the optimal criteria for patient selection, dosage forms, and duration providing the highest benefit and the least potential risk remain to be confirmed. MATERIALS AND METHODS The study population was derived from the Aichi Cohort Study of Prognosis in Patients Newly Initiated into Dialysis, a multicenter prospective cohort study of 1520 incident dialysis patients. According to the VDRA usage status in March 2015 (interim report), the 967 patients surviving after March 2015 were classified into three groups: without VDRA (NV, n = 177), oral VDRA (OV, n = 447), and intravenous VDRA (IV, n = 343). Mortality rates were compared using the log-rank test, and factors contributing to all-cause mortality were examined using both univariate and multivariate Cox proportional hazard regression analyses. RESULTS There were 104 deaths (NV, n = 27; OV, n = 53; IV, n = 24) during the follow-up period (1360 days, median), and significant differences in cumulative survival rates were observed between the three groups (p = 0.010). Moreover, lower all-cause mortality was associated with IV versus NV (hazard ratio, 0.46 [95% confidence interval 0.24-0.89]; p = 0.020). CONCLUSION This study demonstrated the impact of the VDRA dosage form on the short-term survival of incident hemodialysis patients during the introduction period. Our results suggest that relatively early initiation of intravenous VDRA in patients beginning hemodialysis may have some clinical potential.
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Affiliation(s)
- Eri Koshi-Ito
- Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Japan
- The Aichi Cohort Study of Prognosis in Patients Newly Initiated into Dialysis (AICOPP) Group, Aichi, Japan
| | - Daijo Inaguma
- Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Japan
- The Aichi Cohort Study of Prognosis in Patients Newly Initiated into Dialysis (AICOPP) Group, Aichi, Japan
- Department of Internal Medicine, Fujita Health University Bantane Hospital, Nagoya, Japan
| | - Shigehisa Koide
- Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Japan
- The Aichi Cohort Study of Prognosis in Patients Newly Initiated into Dialysis (AICOPP) Group, Aichi, Japan
| | - Kazuo Takahashi
- Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Japan
| | - Hiroki Hayashi
- Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Japan
| | - Naotake Tsuboi
- Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Japan
| | - Midori Hasegawa
- Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Japan
| | - Shoichi Maruyama
- Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan
- The Aichi Cohort Study of Prognosis in Patients Newly Initiated into Dialysis (AICOPP) Group, Aichi, Japan
| | - Yukio Yuzawa
- Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Japan
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21
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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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Banerjee D, Chitalia N, Ster IC, Appelbaum E, Thadhani R, Kaski JC, Goldsmith D. Impact of vitamin D on cardiac structure and function in chronic kidney disease patients with hypovitaminosis D: a randomized controlled trial and meta-analysis. EUROPEAN HEART JOURNAL. CARDIOVASCULAR PHARMACOTHERAPY 2021; 7:302-311. [PMID: 31830258 PMCID: PMC8302255 DOI: 10.1093/ehjcvp/pvz080] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Revised: 11/10/2019] [Accepted: 12/09/2019] [Indexed: 01/08/2023]
Abstract
AIMS Vitamin D deficiency is associated with cardiovascular events in chronic kidney disease (CKD) yet the impact of supplementation is controversial. Previous active vitamin D supplementation studies did not show improvement in cardiac structure or function but the effect of native vitamin D supplementation in CKD patients with low vitamin D levels is unknown. We have addressed this question via both a randomized double-blind prospective study and a meta-analysis of three randomized placebo-controlled studies. METHODS AND RESULTS We conducted a randomized double-blind, placebo-controlled trial of vitamin D supplementation in stable, non-diabetic, CKD three to four patients with circulating vitamin D <75nmol/L, who were receiving treatment with ACEi or ARB and had high-normal left ventricular (LV) mass. Patients were randomized to receive six directly observed doses of 100 000 IU cholecalciferol (n = 25) or matched placebo (n = 23). The primary endpoint was changed in LV mass index (LVMI) over 52 weeks, as assessed by cardiac magnetic resonance imaging. Secondary endpoints included changes in LV ejection fraction (LVEF); LV and right ventricular volumes and left and right atrial area. Vitamin D concentration increased with the administration of cholecalciferol. The change in LVMI with cholecalciferol [median (inter-quartile range), -0.25 g (-7.20 to 5.30)] was no different from placebo [-4.30 g (9.70 to 2.60)]. There was no difference in changes of LVEF; LV and right ventricular volumes and left and right atrial area. The meta-analysis of three 52-week, randomized placebo-controlled studies using active/native vitamin D supplementation showed no differences in LVMI measurements. CONCLUSION Vitamin D supplementation does not have beneficial effects on LV mass in CKD patients.
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Affiliation(s)
- Debasish Banerjee
- Renal and Transplantation Unit, St George’s University Hospital NHS Foundation Trust, G 2.113, Grosvenor Wing, Blackshaw Road, Tooting, London SW17 0QT, UK
- Cardiology Clinical Academic Group, Molecular and Clinical Sciences Research Centre, St George’s University of London, London, UK
| | - Nihil Chitalia
- Cardiology Clinical Academic Group, Molecular and Clinical Sciences Research Centre, St George’s University of London, London, UK
- Renal Medicine, Darent Valley Hospital, Dartford, Kent, UK
| | - Irina Chis Ster
- Institute of Infection and Immunity, St George's University of London, London, UK
| | | | - Ravi Thadhani
- Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Juan Carlos Kaski
- Cardiology Clinical Academic Group, Molecular and Clinical Sciences Research Centre, St George’s University of London, London, UK
| | - David Goldsmith
- Cardiology Clinical Academic Group, Molecular and Clinical Sciences Research Centre, St George’s University of London, London, UK
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Rysz J, Franczyk B, Kujawski K, Sacewicz-Hofman I, Ciałkowska-Rysz A, Gluba-Brzózka A. Are Nutraceuticals Beneficial in Chronic Kidney Disease? Pharmaceutics 2021; 13:231. [PMID: 33562154 PMCID: PMC7915977 DOI: 10.3390/pharmaceutics13020231] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Revised: 01/29/2021] [Accepted: 02/03/2021] [Indexed: 12/18/2022] Open
Abstract
Chronic kidney disease (CKD) is a worldwide health problem in which prevalence is constantly rising. The pathophysiology of CKD is complicated and has not been fully resolved. However, elevated oxidative stress is considered to play a vital role in the development of this disease. CKD is also thought to be an inflammatory disorder in which uremic toxins participate in the development of the inflammatory milieu. A healthy, balanced diet supports the maintenance of a good health status as it helps to reduce the risk of the development of chronic diseases, including chronic kidney disease, diabetes mellitus, and hypertension. Numerous studies have demonstrated that functional molecules and nutrients, including fatty acids and fiber as well as nutraceuticals such as curcumin, steviol glycosides, and resveratrol not only exert beneficial effects on pro-inflammatory and anti-inflammatory pathways but also on gut mucosa. Nutraceuticals have attracted great interest recently due to their potential favorable physiological effects on the human body and their safety. This review presents some nutraceuticals in which consumption could exert a beneficial impact on the development and progression of renal disease as well cardiovascular disease.
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Affiliation(s)
- Jacek Rysz
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland; (J.R.); (B.F.); (K.K.)
| | - Beata Franczyk
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland; (J.R.); (B.F.); (K.K.)
| | - Krzysztof Kujawski
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland; (J.R.); (B.F.); (K.K.)
| | | | | | - Anna Gluba-Brzózka
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland; (J.R.); (B.F.); (K.K.)
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Vahdat S. Vitamin D and Kidney Diseases: A Narrative Review. Int J Prev Med 2020; 11:195. [PMID: 33815719 PMCID: PMC8000170 DOI: 10.4103/ijpvm.ijpvm_54_19] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Accepted: 11/06/2019] [Indexed: 12/12/2022] Open
Abstract
Vitamin D (Vit. D) is among the most important elements of the human body that play pivotal roles in health and disease. It belongs to the fat-soluble secosteroid family, which is provided by either foods or direct exposure to sunlight that converts 7-hydroxycholesterol to the Vit. D precursor. An alternative step is bio-activation, which delivers an active form of Vit. D (Vit. D3), which participates in various noticeable functions including calcium regulation, bone remodeling, fertility, glucose control, and detoxification. The most recent literature is carefully reviewed (2049 articles) and the relative information was collected and discussed meticulously. Inclusion criteria were the articles that mentioned the relationship between Vit. D, adipokine, and kidney disease and exclusion criteria were nonrelevant articles. Vit. D plays several roles in the normal function of the kidney and metabolism. It has been revealed that Vit. D has a crucial impact on kidney disease and that its deficiency leads to kidney dysfunction and further renal disorder. Apart from the direct relationship of Vit. D with kidney disease, the association of adipocytes and adipokines with Vit. D and kidney function has also been studied. The noticeable role of Vit. D in kidney disease is investigated in various studies. It has been found that Vit. D has a pivotal role in kidney function and metabolism. Further study can reveal the better-detailed information about the exact relation of Vit. D and kidney disorders. The aim of the review was to provide a better insight into the exact role of Vit. D and adipokine in the kidney disease.
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Affiliation(s)
- Sahar Vahdat
- Department of Nephrology, Khorshid Hospital, Isfahan Kidney Diseases Research Center, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
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da Silva Canhos MM, de Oliveira RC, Modelli de Andrade LG, Caramori JCT, Barretti P, Martin LC. Association between vitamin D levels and mortality in hemodialysis patients: a cohort study. Ren Fail 2020; 42:225-233. [PMID: 32126885 PMCID: PMC7067165 DOI: 10.1080/0886022x.2020.1735415] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2019] [Revised: 02/12/2020] [Accepted: 02/17/2020] [Indexed: 12/28/2022] Open
Abstract
Introduction: Low vitamin D levels are associated with mortality in hemodialysis (HD) patients; however, the serum vitamin D thresholds are unclear. This study aimed to identify the vitamin D level below which mortality increases in HD patients.Methods: A cohort of HD patients enrolled from January 2014 to January 2017 was evaluated. The variables were analyzed according to the season, namely, summer, winter, and annual average, mortality was the primary outcome. The patients were assigned to vitamin D quintiles, and multivariate Cox regression analysis adjusted for age, ethnicity, gender, body mass index (BMI), inhibitors of the renin-angiotensin system, statin, calcitriol, and antiplatelet drugs use, hemodialysis vintage, hypertension, diabetes mellitus, atherosclerotic disease, and C-reactive protein was performed.Results: There were studied 306 patients. Vitamin D levels of 18.0-23.6 ng/mL (hazard ratio [HR] = 4.30; 95% confidence interval [CI] 1.60-11.54, p = 0.004) and <18.0 ng/mL (HR = 3.83; 95% CI: 1.42-10.35, p = 0.008) in summer and vitamin D levels of 21.5-27.1 ng/mL (HR = 3.70; 95% CI: 1.50-9.11, p = 0.004) and ≤17.5 ng/mL (HR = 2.84; 95% CI: 1.13-7.13, p = 0.026) in winter were associated with mortality. The average annual values of vitamin D associated with all-cause mortality were <17.7 ng/dL (adjusted HR = 4.25, 95% CI: 1.57-11.48, p = 0.004), and between >17.7 ng/dL and ≤23.1 ng/dL (adjusted HR = 3.91, 95% CI: 1.47-10.42, p = 0.006).Conclusions: Annual average vitamin D levels <23.1 ng/mL were associated with higher all-cause mortality, regardless of the confounding variables evaluated.
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Affiliation(s)
- Maryanne Machado da Silva Canhos
- Division of Nephrology, Department of Internal Medicine, Botucatu Medical School, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Rogério Carvalho de Oliveira
- Division of Nephrology, Department of Internal Medicine, Botucatu Medical School, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Luis Gustavo Modelli de Andrade
- Division of Nephrology, Department of Internal Medicine, Botucatu Medical School, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Jacqueline Costa Teixeira Caramori
- Division of Nephrology, Department of Internal Medicine, Botucatu Medical School, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Pasqual Barretti
- Division of Nephrology, Department of Internal Medicine, Botucatu Medical School, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Luis Cuadrado Martin
- Division of Nephrology, Department of Internal Medicine, Botucatu Medical School, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
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Chao JY, Li CY, Wang MC, Kao Yang YH. The use of activated vitamin D and risks of hospitalization for infection and amputation in incident hemodialysis patients in Taiwan: a nationwide population-based cohort study. BMC Nephrol 2020; 21:331. [PMID: 32762673 PMCID: PMC7409709 DOI: 10.1186/s12882-020-01988-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Accepted: 07/29/2020] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Hemodialysis patients have a high risk of mortality. The most common causes of death are cardiovascular disease and infection. The potential hazard or benefit associated with vitamin D use and cardiovascular or infection outcome is poorly characterized. METHODS We conducted a retrospective observational cohort study by recruiting 52,757 patients older than 20 years from Taiwan National Health Insurance Research Database (NHIRD) who initiated maintenance hemodialysis between 2001 and 2009. Patients who were prescribed activated vitamin D before the 360th day from hemodialysis initiation were defined as vitamin D users. The primary outcome of interest includes occurrence of acute myocardial infarction (AMI), ischemic stroke, lower limb amputation, and hospitalization for infection, respectively, while death events are treated as competing events. We conducted competing risk analysis using subdistribution hazard regression model to estimate subdistribution hazard ratios (SHRs) in relation to various outcomes. RESULTS During the median follow-up of 1019 days, the vitamin D users had a lower crude mortality rate, lower incidences of AMI, ischemic stroke, amputation, and hospitalization for infection compared with non-users. Taking into consideration competing events of death, vitamin D users were associated with a lower hazard of lower limb amputation (SHR 0.84 [95% CI, 0.74-0.96]) and hospitalization for infection (SHR 0.90 [95% CI, 0.87-0.94]), but not AMI or ischemic stroke, after adjustment for potential confounders. Subgroup analyses and dose response evaluation both showed a consistent association of activated vitamin D treatment with decreased risk of amputation and infection. CONCLUSION The findings suggest that therapeutic activated vitamin D use in hemodialysis patients may be beneficial for decreasing infection events and amputation, of which the latter is a complication of peripheral vascular disease, rather than reducing major atherosclerotic cardiovascular events such as AMI or ischemic stroke.
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Affiliation(s)
- Jo-Yen Chao
- Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.,Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, No.1, University Road, Tainan, 70101, Taiwan
| | - Chung-Yi Li
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ming-Cheng Wang
- Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.,Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, No.1, University Road, Tainan, 70101, Taiwan
| | - Yea-Huei Kao Yang
- Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, No.1, University Road, Tainan, 70101, Taiwan.
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The effects of vitamin D treatment on glycemic control, serum lipid profiles, and C-reactive protein in patients with chronic kidney disease: a systematic review and meta-analysis of randomized controlled trials. Int Urol Nephrol 2019; 51:1567-1580. [DOI: 10.1007/s11255-019-02236-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Accepted: 07/15/2019] [Indexed: 01/14/2023]
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Chan GCW, Tang SCW. Proteinuria reaffirmed as a risk modifier in diabetic chronic kidney disease. Nephrol Dial Transplant 2019; 33:1873-1874. [PMID: 30032275 DOI: 10.1093/ndt/gfy208] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Accepted: 05/28/2018] [Indexed: 12/18/2022] Open
Affiliation(s)
- Gary C W Chan
- Division of Nephrology, Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Sydney C W Tang
- Division of Nephrology, Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong
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Gembillo G, Cernaro V, Salvo A, Siligato R, Laudani A, Buemi M, Santoro D. Role of Vitamin D Status in Diabetic Patients with Renal Disease. ACTA ACUST UNITED AC 2019; 55:medicina55060273. [PMID: 31200589 PMCID: PMC6630278 DOI: 10.3390/medicina55060273] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2019] [Revised: 06/03/2019] [Accepted: 06/08/2019] [Indexed: 02/07/2023]
Abstract
Diabetes mellitus (DM) poses a major public health problem worldwide, with ever-increasing incidence and prevalence in recent years. The Institute for Alternative Futures (IAF) expects that the total number of people with type 1 and type 2 DM in the United States will increase by 54%, from 19,629,000 to 54,913,000 people, between 2015 and 2030. Diabetic Nephropathy (DN) affects about one-third of patients with DM and currently ranks as the first cause of end-stage kidney disease in the Western world. The complexity of interactions of Vitamin D is directly related with progressive long-term changes implicated in the worsening of renal function. These changes result in a dysregulation of the vitamin D-dependent pathways. Various studies demonstrated a pivotal role of Vitamin D supplementation in regression of albuminuria and glomerulosclerosis, contrasting the increase of glomerular basement membrane thickening and podocyte effacement, with better renal and cardiovascular outcomes. The homeostasis and regulation of the nephron’s function are absolutely dependent from the cross-talk between endothelium and podocytes. Even if growing evidence proves that vitamin D may have antiproteinuric, anti-inflammatory and renoprotective effects in patients with DN, it is still worth investigating these aspects with both more in vitro studies and randomized controlled trials in larger patient series and with adequate follow-up to confirm the effects of long-term vitamin D analogue supplementation in DN and to evaluate the effectiveness of this therapy and the appropriate dosage.
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Affiliation(s)
- Guido Gembillo
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria 98,125 Messina, Italy.
| | - Valeria Cernaro
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria 98,125 Messina, Italy.
| | - Antonino Salvo
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria 98,125 Messina, Italy.
| | - Rossella Siligato
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria 98,125 Messina, Italy.
| | - Alfredo Laudani
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria 98,125 Messina, Italy.
| | - Michele Buemi
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria 98,125 Messina, Italy.
| | - Domenico Santoro
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria 98,125 Messina, Italy.
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Ucak S, Sevim E, Ersoy D, Sivritepe R, Basat O, Atay S. Evaluation of the relationship between microalbuminuria and 25-(OH) vitamin D levels in patients with type 2 diabetes mellitus. Aging Male 2019; 22:116-120. [PMID: 29944055 DOI: 10.1080/13685538.2018.1479385] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND 25-(OH) vitamin D (VD) deficiency has been described as potential risk factor for the development of diabetes in many epidemiological studies. 25-(OH) VD deficiency and insulin resistance associated with this deficiency are common findings in patients with type 2 diabetes mellitus. The objective of this study is to evaluate the relationship between 25-(OH) VD levels and microalbuminuria. METHODS The patients with type 2 diabetes mellitus aged between 40 and 65 years, who were admitted to the diabetes outpatient clinics of our hospital, were evaluated in two different groups. The first group consisted of 119 patients with insufficient 25-(OH) VD levels (10-30 ng/mL) and the second group consisted of 121 patients with 25-(OH) VD deficiency (≤10 ng/mL). The relationship between 25-(OH) VD levels and the level of microalbuminuria was evaluated in the two groups. RESULTS The mean 25-(OH) VD level was 11.5 ng/mL and the mean HbA1c level was 9.1%. When the patient groups were evaluated according to 25-(OH) VD levels, HbA1c values were significantly higher in patients with a 25-(OH) VD level of 10 ng/mL or lower (p = .039). 25-(OH) VD levels were not significantly different between patients with different stages of renal failure (p = .119), whereas the level of microalbuminuria was significantly different (p = .030). CONCLUSIONS This study found that the level of microalbuminuria was significantly higher in patients with 25-(OH) vitamin D deficiency compared to patients with 25-(OH) VD insufficiency.
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Affiliation(s)
- Sema Ucak
- a Department of Internal Medicine , Umraniye Research and Training Center, University of Health Sciences , Istanbul , Turkey
| | - Ecem Sevim
- a Department of Internal Medicine , Umraniye Research and Training Center, University of Health Sciences , Istanbul , Turkey
| | - Damla Ersoy
- a Department of Internal Medicine , Umraniye Research and Training Center, University of Health Sciences , Istanbul , Turkey
| | - Rıdvan Sivritepe
- a Department of Internal Medicine , Umraniye Research and Training Center, University of Health Sciences , Istanbul , Turkey
| | - Okcan Basat
- b Department of Family Medicine , GOP Taksim Research and Training Center, University of Health Sciences , Istanbul , Turkey
| | - Sabri Atay
- c Kartal Uğur Mumcu Family Health Center , Istanbul , Turkey
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Junarta J, Jha V, Banerjee D. Insight into the impact of vitamin D on cardiovascular outcomes in chronic kidney disease. Nephrology (Carlton) 2019; 24:781-790. [DOI: 10.1111/nep.13569] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/21/2019] [Indexed: 02/06/2023]
Affiliation(s)
- Joey Junarta
- Renal and Transplantation UnitSt George's University Hospital NHS Foundation Trust London UK
- Cardiology Clinical Academic GroupMolecular and Clinical Sciences Research Institute, St George's University of London London UK
| | - Vivekanand Jha
- The George Institute of Global Health Oxford UK
- University of Oxford Oxford UK
| | - Debasish Banerjee
- Renal and Transplantation UnitSt George's University Hospital NHS Foundation Trust London UK
- Cardiology Clinical Academic GroupMolecular and Clinical Sciences Research Institute, St George's University of London London UK
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Villa-Bellosta R, Mahillo-Fernández I, Ortíz A, González-Parra E. Questioning the Safety of Calcidiol in Hemodialysis Patients. Nutrients 2019; 11:nu11050959. [PMID: 31035488 PMCID: PMC6566618 DOI: 10.3390/nu11050959] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2019] [Revised: 04/12/2019] [Accepted: 04/23/2019] [Indexed: 12/14/2022] Open
Abstract
Background. Epidemiological studies have suggested a survival benefit for hemodialysis patients on paricalcitol or calcitriol, but nutritional vitamin D supplementation of patients already on vitamin D receptor (VDR) activators is controversial. Methods. This observational retrospective cohort study was conducted with prospectively collected data from all consecutive patients with chronic kidney disease (CKD) who underwent hemodialysis under routine clinical practice conditions for two years. Results. Of the 129 patients, 89 were treated with calcidiol, paricalcitol, and/or calcitriol. The patients with any vitamin D formulation had higher serum concentrations of 25-hydroxy vitamin D and fibroblast growth factor-23 and tended to have higher mortality rates (42% vs. 25%, p = 0.07). On subgroup analysis, any calcidiol treatment or calcidiol combined with paricalcitol associated with significantly higher mortality rates than no treatment (47% and 62.5%, p = 0.043 and 0.008, respectively). The association between calcidiol/paricalcitol treatment and elevated mortality remained significant after adjusting for age, sex, diabetes, C-reactive protein, and hemodialysis vintage. Any calcidiol and calcidiol/paricalcitol treatment exhibited a dose-response relationship with mortality (p for trend: 0.002 and 0.005, respectively). Conclusions. These data draw attention to the hitherto unexplored safety of calcidiol supplementation in patients on hemodialysis, especially in those already on vitamin D. Until clinical trials demonstrate the safety and efficacy of this approach, caution should be exercised when prescribing these patients ≥0.5 calcidiol mg/month.
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Affiliation(s)
- Ricardo Villa-Bellosta
- Renal Division, Fundación Instituto de Investigación Sanitaria Fundación Jiménez Díaz (FIIS-FJD), Avenida Reyes Católicos 2, 29040, Madrid, Spain.
| | - Ignacio Mahillo-Fernández
- Biostatistics and Epidemiology Unit, Fundación Instituto de Investigación Sanitaria Fundación Jiménez Díaz (FIIS-FJD), 29040, Madrid, Spain.
| | - Alberto Ortíz
- Renal Division, Fundación Instituto de Investigación Sanitaria Fundación Jiménez Díaz (FIIS-FJD), Avenida Reyes Católicos 2, 29040, Madrid, Spain.
- Fundación Renal, Íñigo Álvarez de Toledo, 28003 Madrid, Spain.
- Renal Division, IIS-Fundación Jiménez Díaz y Facultad de Medicina, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
| | - Emilio González-Parra
- Renal Division, Fundación Instituto de Investigación Sanitaria Fundación Jiménez Díaz (FIIS-FJD), Avenida Reyes Católicos 2, 29040, Madrid, Spain.
- Renal Division, IIS-Fundación Jiménez Díaz y Facultad de Medicina, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
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Therapeutic targets of vitamin D receptor ligands and their pharmacokinetic effects by modulation of transporters and metabolic enzymes. JOURNAL OF PHARMACEUTICAL INVESTIGATION 2019. [DOI: 10.1007/s40005-019-00429-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Kanno A, Nakayama M, Sanada S, Sato M, Sato T, Taguma Y. Suboptimal initiation predicts short-term prognosis and vulnerability among very elderly patients who start haemodialysis. Nephrology (Carlton) 2019; 24:94-101. [PMID: 29131496 DOI: 10.1111/nep.13194] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/07/2017] [Indexed: 11/26/2022]
Abstract
AIM A recent, growing concern regarding haemodialysis in Japan is a sustained increase in the elderly population. Among very elderly people who start haemodialysis, the prognosis is considered to be poor; however, this has not been fully elucidated. This study aimed to discover the short-term prognosis and related factors in very elderly patients who commence haemodialysis. METHODS Between January 2008 and December 2013, 122 patients aged ≥85 years at haemodialysis initiation were documented in our hospital. Predictors of 90-day and 1-year mortality after haemodialysis initiation were assessed with Cox proportional hazards regression analysis. Selection of covariates for the multivariate model was based on forward stepwise selection using the probability of a likelihood ratio statistics. RESULTS The subjects' mean age was 87.4 ± 2.5 years, and 48% were female. The most common cause of death was infection (38% of patients) and the leading cause of infectious death was pneumonia. The 90-day and 1-year survival rates were 81% and 62%, respectively. Suboptimal initiation was a significant prognostic factor for 90-day [hazard ratio (HR) 3.98, 95% confidence interval (CI) 1.18-13.43] and 1-year [HR 3.19, 95% CI 1.51-6.76] mortality after adjusting for confounders in multivariate analysis. CONCLUSION Very elderly patients who started haemodialysis had a poor prognosis, and suboptimal initiation significantly predicted outcome. Shared decision-making with patients and their families is needed for initiating haemodialysis on the conditions that appropriate information on the expected prognosis is provided.
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Affiliation(s)
- Atsuhiro Kanno
- Department of Nephrology, Japan Community Health Care Organization (JCHO) Sendai Hospital, Sendai, Japan
| | - Masaaki Nakayama
- Research Division of Chronic Kidney Disease and Dialysis Treatment, Tohoku University Hospital, Tohoku University, Sendai, Japan
| | - Satoru Sanada
- Department of Nephrology, Japan Community Health Care Organization (JCHO) Sendai Hospital, Sendai, Japan
| | - Mitsuhiro Sato
- Department of Nephrology, Japan Community Health Care Organization (JCHO) Sendai Hospital, Sendai, Japan
| | - Toshinobu Sato
- Department of Nephrology, Japan Community Health Care Organization (JCHO) Sendai Hospital, Sendai, Japan
| | - Yoshio Taguma
- Department of Nephrology, Japan Community Health Care Organization (JCHO) Sendai Hospital, Sendai, Japan
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Thorsen IS, Bleskestad IH, Åsberg A, Hartmann A, Skadberg Ø, Brede C, Ueland T, Pasch A, Reisæter AV, Gøransson LG. Vitamin D as a risk factor for patient survival after kidney transplantation: A prospective observational cohort study. Clin Transplant 2019; 33:e13517. [DOI: 10.1111/ctr.13517] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2018] [Revised: 02/08/2019] [Accepted: 02/27/2019] [Indexed: 12/15/2022]
Affiliation(s)
- Inga S. Thorsen
- Department of Internal Medicine Stavanger University Hospital Stavanger Norway
- Department of Clinical Medicine University of Bergen Bergen Norway
| | - Inger H. Bleskestad
- Department of Internal Medicine Stavanger University Hospital Stavanger Norway
| | - Anders Åsberg
- Department of Transplantation Medicine Oslo University Hospital Oslo Norway
- Department of Pharmaceutical Biosciences, School of Pharmacy University of Oslo Oslo Norway
- Norwegian Renal Registry Oslo Norway
| | - Anders Hartmann
- Department of Transplantation Medicine Oslo University Hospital Oslo Norway
- Medical Faculty, Institute of Clinical Medicine University of Oslo Oslo Norway
| | - Øyvind Skadberg
- Department of Medical Biochemistry Stavanger University Hospital Stavanger Norway
| | - Cato Brede
- Department of Medical Biochemistry Stavanger University Hospital Stavanger Norway
| | - Thor Ueland
- Medical Faculty, Institute of Clinical Medicine University of Oslo Oslo Norway
- Research Institute of Internal Medicine University of Oslo Oslo Norway
| | | | - Anna V. Reisæter
- Department of Transplantation Medicine Oslo University Hospital Oslo Norway
- Norwegian Renal Registry Oslo Norway
| | - Lasse G. Gøransson
- Department of Internal Medicine Stavanger University Hospital Stavanger Norway
- Department of Clinical Medicine University of Bergen Bergen Norway
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Negrea L. Active Vitamin D in Chronic Kidney Disease: Getting Right Back Where We Started from? KIDNEY DISEASES (BASEL, SWITZERLAND) 2019; 5:59-68. [PMID: 31019920 PMCID: PMC6465695 DOI: 10.1159/000495138] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/25/2018] [Accepted: 11/01/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND The vitamin D system is essential for optimal health in humans. Circulating calcitriol, a key metabolite in maintaining calcium and phosphorus homeostasis, is produced in the kidney. In kidney failure, calcitriol levels progressively decrease, contributing to the development of renal secondary hyperparathyroidism (SHPT). SUMMARY For years, SHPT had a central role in the disturbed mineral metabolism of renal patients. As calcitriol deficiency contributes to SHPT development, treatment with calcitriol or other compounds able to activate the vitamin D receptor (VDR) was one of the mainstays of therapy for renal patients in the last 40 years. In this review, we discuss how the treatment with VDR activators (VDRA) evolved during this time in the United States, as well as the main factors responsible for these changes. KEY MESSAGES Management of SHPT with VDRA in renal patients has undergone a few paradigm shifts over the last 40 years. When treating SHPT, the newly developed therapies as well as VDRA need to be carefully considered and used appropriately. Nephrologists need to use an integrated approach that avoids excessive use of VDRA, ensures replenishment of vitamin D stores, and avoids hypercalcemia and hyperphosphatemia.
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Affiliation(s)
- Lavinia Negrea
- Renal Division, Department of Medicine, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
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Zawierucha J, Malyszko J, Malyszko JS, Prystacki T, Marcinkowski WP, Dryl-Rydzynska T. Three Therapeutic Strategies: Cinacalcet, Paricalcitol or Both in Secondary Hyperparathyroidism Treatment in Hemodialysed Patients During 1-Year Observational Study-A Comparison. Front Endocrinol (Lausanne) 2019; 10:40. [PMID: 30804890 PMCID: PMC6371033 DOI: 10.3389/fendo.2019.00040] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2018] [Accepted: 01/17/2019] [Indexed: 11/13/2022] Open
Abstract
Introduction: Secondary hyperparathyroidism (sHPT) is a common hormonal complication of chronic kidney disease. There are several therapeutic options for sHPT management aiming at calcium-phosphorus balance normalization and decrease of parathormone secretion. Objectives: The aim of this retrospective, observational study was the outcome assessement of three most common therapeutic strategies of secondary hyperparathyroidism treatment with vitamin D receptor activator-paricalcitol, calcimimetic-cinacalcet or both agents administered together during in 12-months period. Methods: One hundred and thirty-one haemodialysed patients with uncontrolled parathyroid hormone secretion have been treated with paricalcitol administered intravenously (group PAR-60 patients) or cinacalcet per os (group CIN-50 patients). The last group (group PAR+CIN-21 patients) received paricalcitol i.v. and oral cinacalcet administered simultaneously. Results: In all groups, the iPTH level decreased significantly, however in group 1 treated with paricalcitol administered intravenously iPTH level decrease was greater than in group 2 treated with cinacalcet and in group 3 treated with paricalcitol and cinacalcet in parallel. The most substantial change of iPTH level was noticed after 3-months of observation. After this period the iPTH level was stabilized and maintained till the end of observation. Safety level of all strategies was comparable. No severe hypercalcemia or hypocalcemia was observed during the whole period of observation. Conclusions: The results of observation show significant advantage of intravenous paricalcitol treatment. Complementing cinacalcet therapy with paricalcitol does not improve treatment outcomes. In case of unsatisfactory results after 3-months treatment, potential continuation should be considered carefully. Among three available therapeutic options, the treatment with paricalcitol i.v. should be considered in all haemodialysed patients with inadequate control of serum PTH level. The second option-with cinacalced administered orally should be considered in PD patients and when severe hypercalcemia occurs.
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Affiliation(s)
| | - Jolanta Malyszko
- Department of Nephrology, Dialysis and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
| | - Jacek S. Malyszko
- First Department of Nephrology and Transplantology With Dialysis Unit, Medical University of Bialystok, Bialystok, Poland
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Cardoso MP, Pereira LAL. Native vitamin D in pre-dialysis chronic kidney disease. Nefrologia 2018; 39:18-28. [PMID: 30274806 DOI: 10.1016/j.nefro.2018.07.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2018] [Accepted: 07/12/2018] [Indexed: 02/08/2023] Open
Abstract
Chronic kidney disease patients have a high prevalence of vitamin D insufficiency/deficiency. Vitamin D deficiency has been associated with a variety of bone, metabolic and cardiovascular disorders. However, the role of native vitamin D supplementation (ergocalciferol, cholecalciferol or calcifediol) remains unclear in chronic kidney disease (CKD), particularly in the pre-dialytic phase. Several international guidelines have been developed on CKD-Mineral and Bone Disorder, but the optimal strategy for native vitamin D supplementation and its clinical benefit remains a subject of debate in the scientific community. This paper aims to review the available literature, including randomized clinical trials that evaluated the effects of native vitamin D supplementation on pre-dialysis CKD on biochemical and clinically relevant outcomes.
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Affiliation(s)
- Mariana P Cardoso
- Faculty of Medicine of University of Porto, Al. Prof. Hernâni Monteiro, 4200-451 Porto, Portugal.
| | - Luciano A L Pereira
- Institute of Investigation and Innovation in Health, University of Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; Nephrology and Infeciology Group, INEB-National Institute of Biomedical Engineer, University of Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; Department of Nephrology, São João Hospital Center, Al. Prof. Hernâni Monteiro, 4200-451 Porto, Portugal
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Lundwall K, Jacobson SH, Jörneskog G, Spaak J. Treating endothelial dysfunction with vitamin D in chronic kidney disease: a meta-analysis. BMC Nephrol 2018; 19:247. [PMID: 30253741 PMCID: PMC6156877 DOI: 10.1186/s12882-018-1042-y] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2018] [Accepted: 09/10/2018] [Indexed: 12/14/2022] Open
Abstract
Background Vitamin D deficiency is common in patients with chronic kidney disease (CKD), and is associated with endothelial dysfunction and cardiovascular disease. We performed a meta-analysis to assess the effect of vitamin D treatment on flow mediated vasodilation (FMD) in CKD patients. Methods PubMed/Medline, Web of Science, Embase and Cochrane trials and reviews were searched systematically for randomized controlled trials (RCT:s) using any vitamin D compound, at any stage of CKD, with FMD as outcome. Fixed and random effects models were performed using the standardized mean difference effect size post treatment for each trial. Heterogeneity was assessed by I2 statistics. Results 4 trials were included, comprising 305 patients. One used both 1 and 2 μg for two intervention groups and was therefore split in two during the analysis. Patients in the included trials had a mean age of 44–65 years and were all in CKD 3 to 4. One study used cholecalciferol, the others all used paricalcitol as treatment. Study duration was 12–16 weeks. Intervention with vitamin D was associated with ameliorated FMD (STANDmean ES 0.78, 95% CI 0.55–1.01) in a fixed model. Heterogeneity was substantial (I2 = 84%). Secondary analysis with random model analysis also showed significant results. Conclusions Short term intervention with vitamin D is associated with improvements in endothelial function, as measured by FMD. This indicates positive effects of vitamin D on vascular disease in CKD. Limitations of this meta-analysis are the small number of studies performed, and the short duration of intervention. Electronic supplementary material The online version of this article (10.1186/s12882-018-1042-y) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Kristina Lundwall
- Department of Clinical Sciences, Danderyd University Hospital, Karolinska Institutet, Stockholm, Sweden. .,Department of Cardiology, Danderyd University Hospital, 182 88, Stockholm, Sweden.
| | - Stefan H Jacobson
- Department of Clinical Sciences, Danderyd University Hospital, Karolinska Institutet, Stockholm, Sweden
| | - Gun Jörneskog
- Department of Clinical Sciences, Danderyd University Hospital, Karolinska Institutet, Stockholm, Sweden
| | - Jonas Spaak
- Department of Clinical Sciences, Danderyd University Hospital, Karolinska Institutet, Stockholm, Sweden.,Department of Cardiology, Danderyd University Hospital, 182 88, Stockholm, Sweden
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Ito E, Inaguma D, Koide S, Takahashi K, Hayashi H, Hasegawa M, Yuzawa Y. Effect of combined vitamin D receptor activator and lanthanum carbonate on serum fibroblast growth factor 23 level in predialysis patients (CVD-LAF study): design and method. Clin Exp Nephrol 2018; 22:1309-1314. [PMID: 29748907 DOI: 10.1007/s10157-018-1584-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Accepted: 04/19/2018] [Indexed: 11/26/2022]
Abstract
BACKGROUND Whether vitamin D receptor activator (VDRA) use is beneficial in chronic kidney disease (CKD) is unclear, because it is possible that VDRA increases serum fibroblast growth factor 23 (FGF23) levels. We will conduct a randomized controlled trial in predialysis patients to determine the effect of VDRA alone or in combination with lanthanum carbonate (LC) on serum FGF23 levels. METHODS This is a single-center, open-label, randomized controlled trial. Enrollment will commence February 1, 2018, using the following inclusion criteria: (1) age ≥ 20 years, (2) CKD with an estimated glomerular filtration rate of 10-45 mL/min/1.73 m2, (3) serum adjusted calcium level < 9.5 mg/dL, (4) serum phosphate level 4.0-6.0 mg/dL, and (5) serum intact parathyroid hormone (PTH) level ≥ 60 pg/mL. Study patients will be randomized 1:1 to receive alfacalcidol alone or in combination with LC. The initial dose of alfacalcidol will be 0.25-0.5 µg once a day according to serum adjusted calcium level. The initial dose of LC will be 250 mg once a day. We will measure serum intact and C-terminal FGF23 at 0, 4, 8, 12, 24, and 52 weeks. The primary outcome will be serum FGF23 level at 24 weeks compared with baseline. DISCUSSION This study aims to determine whether low-dose oral VDRA increases serum FGF23 level and whether the combination of VDRA and LC inhibits this increase. The results will be useful in the management of CKD-mineral and bone disorder in predialysis patients. TRIAL REGISTRATION UMIN000030503. Registered 20 January 2018.
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Affiliation(s)
- Eri Ito
- Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
| | - Daijo Inaguma
- Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
| | - Shigehisa Koide
- Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
| | - Kazuo Takahashi
- Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
| | - Hiroki Hayashi
- Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
| | - Midori Hasegawa
- Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
| | - Yukio Yuzawa
- Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
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Isaksson E, Almquist M, Seeberger A, Sterner G. Is low pre-transplant parathyroid hormone a risk marker for cardiovascular disease in long-term follow-up of renal transplant recipients? Clin Exp Nephrol 2018; 22:1188-1197. [PMID: 29478201 PMCID: PMC6154172 DOI: 10.1007/s10157-018-1543-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2017] [Accepted: 02/11/2018] [Indexed: 11/30/2022]
Abstract
Background Secondary hyperparathyroidism and altered levels of parathyroid hormone (PTH) are associated with vascular events in chronic kidney disease. After renal transplantation, this association is not clear. Pre-transplant parathyroidectomy (PTX) is common, but post-transplant data are scarce. We aimed to study the effect of PTH at the time of transplantation on risk of post-transplant vascular events in renal transplant recipients with and without pre-transplant PTX. Methods 258 patients from two Swedish transplant units were followed for 6 years. Separate analyses were made for patients with or without pre-transplant PTX. Patients with no pre-transplant PTX were stratified by quartiles of PTH at time of transplantation and patients with pre-transplant PTX were stratified by above and below median levels of PTH at time of transplantation. Hazard ratios for vascular events, mortality, and graft failure were calculated in adjusted Cox regression models. Results In patients with no pre-transplant PTX, the lowest quartile of PTH at transplantation had a higher risk of cardiovascular events compared to quartile 3 with an adjusted hazard ratio (95% CI) of 2.63 (1.04–6.67). In patients with pre-transplant PTX, the group below median of PTH had a higher risk of cardiovascular events with an adjusted hazard ratio (95% CI) of 18.15 (1.62–203.82) compared to patients above median of PTH. Conclusion Low levels of parathyroid hormone before transplantation were associated with increased risk of post-transplant vascular events both in patients with and without pre-transplant parathyroidectomy. Any conclusions on causal or direct effect of PTH on outcome cannot be drawn from this observational study.
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Affiliation(s)
- Elin Isaksson
- Department of Clinical Sciences, Faculty of Medicine, Lund University, Malmö, Sweden. .,Department of Urology, Faculty of Medicine, Skåne University Hospital, Lund University, Jan Waldenströms gata 5, 20502, Malmö, SE, Sweden.
| | - Martin Almquist
- Department of Clinical Sciences Lund, Skåne University Hospital, Lund University, Lund, Sweden.,Department of Surgery Section of Endocrine and Sarcoma Lund, Skane University Hospital, Lund, Sweden
| | - Astrid Seeberger
- Department of Nephrology Huddinge, Faculty of Medicine, Karolinska University Hospital, Karolinska University, Solna, Sweden
| | - Gunnar Sterner
- Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden.,Department of Nephrology, Skane University Hospital, Malmö, Sweden
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42
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Hallan S, Afkarian M, Zelnick LR, Kestenbaum B, Sharma S, Saito R, Darshi M, Barding G, Raftery D, Ju W, Kretzler M, Sharma K, de Boer IH. Metabolomics and Gene Expression Analysis Reveal Down-regulation of the Citric Acid (TCA) Cycle in Non-diabetic CKD Patients. EBioMedicine 2017; 26:68-77. [PMID: 29128444 PMCID: PMC5832558 DOI: 10.1016/j.ebiom.2017.10.027] [Citation(s) in RCA: 110] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2017] [Revised: 10/27/2017] [Accepted: 10/28/2017] [Indexed: 01/17/2023] Open
Abstract
Chronic kidney disease (CKD) is a public health problem with very high prevalence and mortality. Yet, there is a paucity of effective treatment options, partly due to insufficient knowledge of underlying pathophysiology. We combined metabolomics (GCMS) with kidney gene expression studies to identify metabolic pathways that are altered in adults with non-diabetic stage 3-4 CKD versus healthy adults. Urinary excretion rate of 27 metabolites and plasma concentration of 33 metabolites differed significantly in CKD patients versus controls (estimate range-68% to +113%). Pathway analysis revealed that the citric acid cycle was the most significantly affected, with urinary excretion of citrate, cis-aconitate, isocitrate, 2-oxoglutarate and succinate reduced by 40-68%. Reduction of the citric acid cycle metabolites in urine was replicated in an independent cohort. Expression of genes regulating aconitate, isocitrate, 2-oxoglutarate and succinate were significantly reduced in kidney biopsies. We observed increased urine citrate excretion (+74%, p=0.00009) and plasma 2-oxoglutarate concentrations (+12%, p=0.002) in CKD patients during treatment with a vitamin-D receptor agonist in a randomized trial. In conclusion, urinary excretion of citric acid cycle metabolites and renal expression of genes regulating these metabolites were reduced in non-diabetic CKD. This supports the emerging view of CKD as a state of mitochondrial dysfunction.
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Affiliation(s)
- Stein Hallan
- Center for Renal Translational Medicine/Institute for Metabolomic Medicine, University of California San Diego, San Diego, CA, United States; Department of Clinical and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway; Department of Nephrology, St. Olav Hospital, Trondheim, Norway.
| | - Maryam Afkarian
- Kidney Research Institute, University of Washington, Seattle, WA, United States; Division of Nephrology, Department of Medicine, University of California, Davis, CA, United States
| | - Leila R Zelnick
- Kidney Research Institute, University of Washington, Seattle, WA, United States; Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA, United States
| | - Bryan Kestenbaum
- Kidney Research Institute, University of Washington, Seattle, WA, United States; Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA, United States
| | - Shoba Sharma
- University of Texas Health San Antonio, San Antonio, TX, United States
| | - Rintaro Saito
- Center for Renal Translational Medicine/Institute for Metabolomic Medicine, University of California San Diego, San Diego, CA, United States
| | - Manjula Darshi
- Center for Renal Translational Medicine/Institute for Metabolomic Medicine, University of California San Diego, San Diego, CA, United States
| | - Gregory Barding
- Northwest Metabolomics Research Center, University of Washington, Seattle, WA, United States
| | - Daniel Raftery
- Northwest Metabolomics Research Center, University of Washington, Seattle, WA, United States
| | - Wenjun Ju
- Division of Nephrology, Department of Medicine, University of Michigan, Ann Arbor, MI, United States; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, United States
| | - Matthias Kretzler
- Division of Nephrology, Department of Medicine, University of Michigan, Ann Arbor, MI, United States; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, United States
| | - Kumar Sharma
- Center for Renal Translational Medicine/Institute for Metabolomic Medicine, University of California San Diego, San Diego, CA, United States; Department of Nephrology and Hypertension, Veterans Administration San Diego HealthCare System, San Diego, CA, United States
| | - Ian H de Boer
- Kidney Research Institute, University of Washington, Seattle, WA, United States; Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA, United States
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Inaguma D, Ito E, Koide S, Takahashi K, Hayashi H, Hasegawa M, Yuzawa Y. Combination Therapy with Renin-Angiotensin System Blockers and Vitamin D Receptor Activators for Predialysis Patients Is Associated with the Incidence of Cardiovascular Events after Dialysis Initiation: A Multicenter Nonrandomized Prospective Cohort Study. Cardiorenal Med 2017; 8:71-81. [PMID: 29344028 PMCID: PMC5757592 DOI: 10.1159/000479894] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2017] [Accepted: 07/26/2017] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Several human studies reported that the combined use of renin-angiotensin system blockers (RASBs) and vitamin D receptor activators (VDRAs) resulted in decreased urinary protein excretion. However, it is unknown whether this combination therapy influences the incidence of cardiovascular (CV) events in dialysis patients. METHODS The study was a multicenter nonrandomized prospective cohort analysis including 1,518 patients. Patients were classified into 4 groups based on medications prescribed before dialysis initiation: those who did not receive RASBs or oral VDRAs (N group), those receiving only RASBs, those receiving only VDRAs, and those receiving a combination of RASBs and VDRAs (RD group). CV events after dialysis initiation were compared using the log-rank test. Factors contributing to the incidence of CV events were examined using multivariate Cox proportional hazard regression analysis. RESULTS Significant differences were observed in the incidence of CV events and all-cause mortality between the 4 groups (p = 0.021 and p = 0.001, respectively). Cox proportional hazard analysis revealed that the incidence of CV events was significantly lower in the RD group than in the N group (hazard ratio [HR] = 0.65, 95% confidence interval [CI]: 0.50-0.86, p = 0.002). Multivariate analysis revealed that the incidence of CV events was significantly lower in the RD group than in the N group (HR = 0.66, 95% CI: 0.47-0.93, p = 0.016). CONCLUSION Combination therapy with RASBs and VDRAs in patients before dialysis initiation was associated with a reduction in CV events during maintenance dialysis.
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Affiliation(s)
- Daijo Inaguma
- Fujita Health University School of Medicine, Toyoake, Japan
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Levin A, Tang M, Perry T, Zalunardo N, Beaulieu M, Dubland JA, Zerr K, Djurdjev O. Randomized Controlled Trial for the Effect of Vitamin D Supplementation on Vascular Stiffness in CKD. Clin J Am Soc Nephrol 2017; 12:1447-1460. [PMID: 28550081 PMCID: PMC5586581 DOI: 10.2215/cjn.10791016] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2016] [Accepted: 04/17/2017] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND OBJECTIVES Vitamin D is implicated in vascular health in CKD. This study compared placebo, calcifediol, and calcitriol treatment with changes in vascular stiffness, BP, proteinuria, mineral metabolism parameters, C-reactive protein, and fibroblast growth factor 23 in patients with stable CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We conducted a double-blind, randomized controlled trial in out-patient CKD clinics in Vancouver, Canada, from February of 2011 to August of 2014, enrolling 119 patients with an eGFR of 15-45 ml/min per 1.73 m2. Change in pulse wave velocity (PWV) was measured after 6 months of treatment with a fixed dose of oral calcifediol (5000 IU 25-hydroxyvitamin D3), calcitriol (0.5 µg 1,25-dihydroxyvitamin D3), or placebo, thrice weekly. RESULTS Eighty-seven participants were evaluated. Mean age was 66 years, 71% were men, 40% were diabetic, and mean baseline PWV was 11.5 m/s (SD=3.9 m/s). After 6 months, the PWV decreased in the calcifediol group (mean change, -1.1; 95% confidence interval [95% CI], -2.2 to 0.1 m/s), remained unchanged in the calcitriol group (mean change, 0.2; 95% CI, -0.9 to 1.4 m/s), and increased in the placebo group (mean change, 1.1; 95% CI, -0.1 to 2.2 m/s). The overall P value for between-arm changes was 0.03. Absolute PWV change was significantly different between groups (P=0.04): the combined vitamin D treatment group saw decreased PWV (mean change, -0.4; 95% CI, -1.2 to 0.4 m/s) whereas the placebo group saw increased PWV (mean change, +1.1; 95% CI, -0.1 to 2.2 m/s). The treatment group demonstrated significantly decreased serum parathyroid hormone (mean difference, -0.5; 95% CI, -0.7 to -0.3 ln[pg/ml]; P<0.001) and increased calcium (mean difference, 0.4; 95% CI, -0.1 to 0.7 mg/dl; P=0.02). In observational analysis, participants in the highest 25-hydroxyvitamin D tertile at trial end had significant decreases in PWV (mean change, -1.0; 95% CI, -2.0 to 0.0 m/s) compared with the middle and lowest tertiles (P<0.01). Side effects were minor and rare. CONCLUSIONS Six months of supplemental vitamin D analogs at fixed doses may achieve a reduction of PWV in patients with advanced CKD. Because the treatment effect was attenuated when baseline PWV was included as a covariate, these findings should be replicated in larger populations and further studied.
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Affiliation(s)
- Adeera Levin
- Division of Nephrology
- Department of Medicine, and
| | - Mila Tang
- Nephrology Research, St. Paul's Hospital, and
- BC Renal Agency, Vancouver, Canada
| | | | | | - Monica Beaulieu
- Division of Nephrology
- Department of Medicine, and
- BC Renal Agency, Vancouver, Canada
| | - Joshua A. Dubland
- Department of Medicine, and
- Centre for Heart and Lung Innovation, University of British Columbia
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Toussaint ND, Ruderman I. What Is the Role of Vitamin D Supplementation on Vascular Health in CKD? Clin J Am Soc Nephrol 2017; 12:1377-1379. [PMID: 28784658 PMCID: PMC5586577 DOI: 10.2215/cjn.07170717] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Nigel D. Toussaint
- Department of Nephrology, The Royal Melbourne Hospital, Parkville, Victoria, Australia; and
- Department of Medicine at Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia
| | - Irene Ruderman
- Department of Nephrology, The Royal Melbourne Hospital, Parkville, Victoria, Australia; and
- Department of Medicine at Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia
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Xie Y, Su P, Sun Y, Zhang H, Zhao R, Li L, Meng L. Comparative efficacy and safety of paricalcitol versus vitamin D receptor activators for dialysis patients with secondary hyperparathyroidism: a meta-analysis of randomized controlled trials. BMC Nephrol 2017; 18:272. [PMID: 28841848 PMCID: PMC5574209 DOI: 10.1186/s12882-017-0691-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2016] [Accepted: 08/18/2017] [Indexed: 11/20/2022] Open
Abstract
Background Secondary hyperparathyroidism (SHPT) is a severe complication for dialysis patients. Vitamin D receptor activators (VDRAs) are used to treat SHPT, but the comparative efficacy and safety between paricalcitol and other vitamin D receptor activators for management of SHPT in dialysis patients has been unproven. Methods We searched PubMed, Embase, and the Cochrane Library for the time period through June 2017 to identify randomized controlled trials that evaluated paricalcitol compared with other VDRAs for treatment of SHPT. The primary outcome was the percentage of patients with target reduction of intact parathyroid hormone (iPTH) from baseline. Secondary outcomes included incidences of hypercalcemia and hyperphosphatemia. The random-effects model was used to estimate relative risks (RRs) with 95% confidence intervals (CIs). Results Eight studies (N = 759) were eligible for final inclusion. Compared with other VDRAs, no significant differences were found in the percentage of patients with target reduction of intact parathyroid hormone (iPTH) from baseline for paricalcitol treatment of SHPT in dialysis patients (RR, 1.01; 95% CI, 0. 87–1.18; p = 0.85). There were no differences in the incidence of hypercalcemia (RR, 0.95; 95% CI, 0.74–1.21; p = 0. 65) and hyperphosphatemia (RR, 0.94; 95% CI, 0.77–1.16; p = 0.58). Conclusions The presently available evidence is insufficient to draw a conclusion regarding whether paricalcitol therapy has a comparative efficacy and safety over other VDRAs for treating dialysis patients with SHPT. Large-sample, well-conducted, high-quality RCTs with patient-level outcomes (i.e., mortality) are urgently needed. Electronic supplementary material The online version of this article (10.1186/s12882-017-0691-6) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Yifeng Xie
- Department of Nephrology, The Third Affiliated Hospital of Guangxi University of Chinese medicine, No.32, Jie-Fang-Bei Road, Cheng-Zhong District, Liuzhou, Guangxi, 545001, People's Republic of China.
| | - Peiling Su
- Department of Nephrology, The Third Affiliated Hospital of Guangxi University of Chinese medicine, No.32, Jie-Fang-Bei Road, Cheng-Zhong District, Liuzhou, Guangxi, 545001, People's Republic of China
| | - Yifan Sun
- Department of Clinical Laboratory, The Third Affiliated Hospital of Guangxi University of Chinese medicine, Liuzhou, Guangxi, People's Republic of China
| | - Hongsheng Zhang
- Department of Orthopaedics, The Third Affiliated Hospital of Guangxi University of Chinese medicine, Liuzhou, Guangxi, People's Republic of China
| | - Rong Zhao
- Department of Nephrology, The Third Affiliated Hospital of Guangxi University of Chinese medicine, No.32, Jie-Fang-Bei Road, Cheng-Zhong District, Liuzhou, Guangxi, 545001, People's Republic of China
| | - Liang Li
- Department of Nephrology, The Third Affiliated Hospital of Guangxi University of Chinese medicine, No.32, Jie-Fang-Bei Road, Cheng-Zhong District, Liuzhou, Guangxi, 545001, People's Republic of China
| | - Lanfen Meng
- Department of Nephrology, The Third Affiliated Hospital of Guangxi University of Chinese medicine, No.32, Jie-Fang-Bei Road, Cheng-Zhong District, Liuzhou, Guangxi, 545001, People's Republic of China
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Wang M, Obi Y, Streja E, Rhee CM, Lau WL, Chen J, Hao C, Hamano T, Kovesdy CP, Kalantar-Zadeh K. Association of Parameters of Mineral Bone Disorder with Mortality in Patients on Hemodialysis according to Level of Residual Kidney Function. Clin J Am Soc Nephrol 2017; 12:1118-1127. [PMID: 28487345 PMCID: PMC5498357 DOI: 10.2215/cjn.11931116] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2016] [Accepted: 04/04/2017] [Indexed: 11/23/2022]
Abstract
BACKGROUND AND OBJECTIVES The relationship between mineral and bone disorders and survival according to residual kidney function status has not been previously studied in patients on hemodialysis. We hypothesized that residual kidney function, defined by renal urea clearance, modifies the association between mineral and bone disorder parameters and mortality. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The associations of serum phosphorus, albumin-corrected calcium, intact parathyroid hormone, and alkaline phosphatase with all-cause mortality were examined across three strata (<1.5, 1.5 to <3.0, and ≥3.0 ml/min per 1.73 m2) of baseline residual renal urea clearance using Cox models adjusted for clinical characteristics and laboratory measurements in 35,114 incident hemodialysis patients from a large United States dialysis organization over the period of 2007-2011. RESULTS A total of 8102 (23%) patients died during the median follow-up of 1.3 years (interquartile range, 0.6-2.3 years). There was an incremental mortality risk across higher serum phosphorus concentrations, which was pronounced among patients with higher residual renal urea clearance (Pinteraction=0.001). Lower concentrations of serum intact parathyroid hormone were associated with higher mortality among patients with low residual renal urea clearance (i.e., <1.5 ml/min per 1.73 m2), whereas higher concentrations showed a higher mortality risk among patients with greater residual renal urea clearance (i.e., ≥1.5 ml/min per 1.73 m2; Pinteraction<0.001). Higher serum corrected total calcium and higher alkaline phosphatase concentrations consistently showed higher mortality risk (Ptrend<0.001 for both) irrespective of residual renal urea clearance strata (Pinteraction=0.34 and Pinteraction=0.53, respectively). CONCLUSIONS Residual kidney function modified the mortality risk associated with serum phosphorus and intact parathyroid hormone among incident hemodialysis patients. Future studies are needed to examine whether taking account for residual kidney function into the assessment of mortality risk associated with serum phosphorus and intact parathyroid hormone improves patient management and clinical outcomes in the hemodialysis population.
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Affiliation(s)
- Mengjing Wang
- Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine Medical Center, Orange, California
- Division of Nephrology, Huashan Hospital, Fudan University, Shanghai, China
| | - Yoshitsugu Obi
- Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine Medical Center, Orange, California
| | - Elani Streja
- Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine Medical Center, Orange, California
| | - Connie M. Rhee
- Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine Medical Center, Orange, California
| | - Wei Ling Lau
- Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine Medical Center, Orange, California
| | - Jing Chen
- Division of Nephrology, Huashan Hospital, Fudan University, Shanghai, China
| | - Chuanming Hao
- Division of Nephrology, Huashan Hospital, Fudan University, Shanghai, China
| | - Takayuki Hamano
- Department of Comprehensive Kidney Disease Research, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Csaba P. Kovesdy
- Division of Nephrology, University of Tennessee Health Science Center, Memphis, Tennessee
- Nephrology Section, Memphis Veterans Affairs Medical Center, Memphis, Tennessee
| | - Kamyar Kalantar-Zadeh
- Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine Medical Center, Orange, California
- Department of Epidemiology, Fielding School of Public Health at University of California, Los Angeles, Los Angeles, California; and
- Nephrology Section, Tibor Rubin Veterans Affairs Medical Center, Long Beach, California
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Kumar V, Yadav AK, Lal A, Kumar V, Singhal M, Billot L, Gupta KL, Banerjee D, Jha V. A Randomized Trial of Vitamin D Supplementation on Vascular Function in CKD. J Am Soc Nephrol 2017; 28:3100-3108. [PMID: 28667080 DOI: 10.1681/asn.2017010003] [Citation(s) in RCA: 87] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2017] [Accepted: 05/03/2017] [Indexed: 12/11/2022] Open
Abstract
Vitamin D deficiency associates with mortality in patients with CKD, and vitamin D supplementation might mitigate cardiovascular disease risk in CKD. In this randomized, double-blind, placebo-controlled trial, we investigated the effect of cholecalciferol supplementation on vascular function in 120 patients of either sex, aged 18-70 years, with nondiabetic CKD stage 3-4 and vitamin D deficiency (serum 25-hydroxyvitamin D ≤20 ng/ml). We randomized patients using a 1:1 ratio to receive either two directly observed oral doses of cholecalciferol (300,000 IU) or matching placebo at baseline and 8 weeks. The primary outcome was change in endothelium-dependent brachial artery flow-mediated dilation at 16 weeks. Secondary outcome measures included changes in pulse wave velocity and circulating biomarkers. Cholecalciferol supplementation significantly increased endothelium-dependent brachial artery flow-mediated dilation at 16 weeks, whereas placebo did not (between-group difference in mean change: 5.49%; 95% confidence interval, 4.34% to 6.64%; P<0.001). Intervention also led to significant favorable changes in pulse wave velocity and circulating IL-6 levels. Thus, in nondiabetic patients with stage 3-4 CKD and vitamin D deficiency, vitamin D supplementation may improve vascular function. This study is registered with the Clinical Trials Registry of India (no.: CTRI/2013/05/003648).
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Affiliation(s)
| | | | - Anupam Lal
- Radiodiagnosis, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | | | - Manphool Singhal
- Radiodiagnosis, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Laurent Billot
- George Institute for Global Health, Sydney, New South Wales, Australia.,Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
| | | | - Debasish Banerjee
- Renal and Transplantation Unit, St. George's University Hospitals National Health Service Foundation Trust, London, UK.,Molecular and Clinical Sciences Research Institute, St. George's, University of London, London, UK
| | - Vivekanand Jha
- Departments of Nephrology and .,George Institute for Global Health, New Delhi, India; and.,George Institute for Global Health, University of Oxford, Oxford, UK
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Psychometric Properties of a Developed Questionnaire to Assess Knowledge, Attitude and Practice Regarding Vitamin D (D-KAP-38). Nutrients 2017; 9:nu9050471. [PMID: 28481302 PMCID: PMC5452201 DOI: 10.3390/nu9050471] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2017] [Revised: 04/22/2017] [Accepted: 04/23/2017] [Indexed: 12/17/2022] Open
Abstract
The aim of this study was to develop a valid and reliable questionnaire to assess vitamin D-related knowledge, attitude and practices in Tehranian adults, who may be at increased risk of vitamin D deficiency. This study was conducted on 572 individuals, aged ≥20 years from public health care centers in Tehran, Iran. Based on results of a literature review and in-depth interviews, the 38-item vitamin D-related KAP questionnaire (D-KAP-38) with four subscales was developed: (1) general knowledge; (2) nutritional knowledge; (3) attitudes; (4) behaviors. Validity of the D-KAP-38 questionnaire was assessed, utilizing face, content, and construct validity methods. Internal consistency was calculated to assess reliability of the current developed questionnaire. A total of 572 (54.1% female) adults, aged 30.2 ± 7.9 years, participated in the study. All items were perceived as relevant and comprehendible by participants. Content validity was confirmed by a panel of experts. The internal consistency, as measured by Cronbach's alpha coefficients, exceeded the minimum reliability standard of 0.60 for four subscales. Exploratory factor analysis suggested a four-factor construct and the results of the confirmatory factor analysis indicated acceptable fit indices for the proposed model. No ceiling effects were observed except for general knowledge (1.2%). Floor effects detected were 0%, 1.1%, 2.4%, and 8.7% for practice, attitude, general knowledge, and nutrition knowledge, respectively. General knowledge had the highest score (79.59 ± 14.52) and nutrition knowledge had the lowest (42.58 ± 20.40), among the four sub-scales. Results confirm the initial validity and reliability of D-KAP-38 questionnaire. Further investigations in different populations are recommended.
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Portillo MR, Rodríguez-Ortiz ME. Secondary Hyperparthyroidism: Pathogenesis, Diagnosis, Preventive and Therapeutic Strategies. Rev Endocr Metab Disord 2017; 18:79-95. [PMID: 28378123 DOI: 10.1007/s11154-017-9421-4] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Uremic secondary hyperparathyroidism is a multifactorial and complex disease often present in advanced stages of chronic kidney disease. The accumulation of phosphate, the increased FGF23 levels, the reduction in active vitamin D production, and the tendency to hypocalcemia are persistent stimuli for the development and progression of parathyroid hyperplasia with increased secretion of PTH. Parathyroid proliferation may become nodular mainly in cases of advanced hyperparathyroidism. The alterations in the regulation of mineral metabolism, the development of bone disease and extraosseous calcifications are essential components of chronic kidney disease-mineral and bone disorder and have been associated with negative outcomes. The management of hyperparathyroidism includes the correction of vitamin D deficiency and control of serum phosphorus and PTH without inducing hypercalcemia. An update of the leading therapeutic tools available for the prevention and clinical management of secondary hyperparathyroidism, its diagnosis, and the main mechanisms and factors involved in the pathogenesis of the disease will be described in this review.
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Affiliation(s)
- Mariano Rodríguez Portillo
- Nephrology Service, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofía University Hospital/University of Córdoba, Avda. Menéndez Pidal, S/N, 14004, Córdoba, Spain.
- REDinREN, Madrid, Spain.
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