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Ramírez Stieben LA, Brance ML, Belardinelli MV, Bolzán D, Pustilnik E, Feldman RN, Brun LR. PTH levels and establishment of reference intervals: Impact of vitamin D and renal function. ENDOCRINOL DIAB NUTR 2025; 72:101527. [PMID: 39978869 DOI: 10.1016/j.endien.2025.101527] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Accepted: 09/02/2024] [Indexed: 02/22/2025]
Abstract
INTRODUCTION Parathyroid hormone (PTH) and vitamin D are essential components in mineral metabolism. Our aims were to estimate the thresholds of 25-hydroxyvitamin D [25(OH)D] and estimated glomerular filtration rate (eGFR) that inhibit PTH, establish PTH reference intervals (RIs), and the stratify need based on age and gender. MATERIALS AND METHODS We conducted a cross-sectional study on participants older than 18 years. Segmented regressions (SR) were performed to determine the thresholds of 25(OH)D and eGFR in relation to PTH levels. Multivariate regression was used to evaluate the associations between PTH and 25(OH)D, gender, age, eGFR, and season. To establish the PTH RIs, extreme percentiles were calculated. RESULTS A total of 2794 subjects were analyzed (women, 77.56%). Multivariate regression indicated that age, gender, 25(OH)D, and eGFR explained PTH variation. SR demonstrated that PTH stabilized when eGFR>46.64mL/min/1.73m2, and PTH increased when 25(OH)D was <15.8ng/mL. Stratification by gender and age revealed different RIs, with women and over 70 years showing higher limits. CONCLUSION Our study suggests a stabilization point in PTH with an eGFR>46.64mL/min/1.73m2, indicating a significant interaction between renal function and PTH regulation. Additionally, the significant increase in PTH in individuals with 25(OH)D<15.8ng/mL emphasizes the importance of vitamin D in regulation. An association between age and PTH was also evident, particularly a substantial increase after the age of 70. Finally, we established the need to define partitioned RIs for PTH based on age and gender.
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Affiliation(s)
- Luis Agustín Ramírez Stieben
- Servicio de Endocrinología del Grupo Gamma, Rosario, Argentina; Reumatología y Enfermedades Óseas, Rosario, Argentina; Laboratorio de Biología Ósea de la Facultad de Ciencias Médicas de la Universidad Nacional de Rosario, Argentina.
| | - María Lorena Brance
- Reumatología y Enfermedades Óseas, Rosario, Argentina; Laboratorio de Biología Ósea de la Facultad de Ciencias Médicas de la Universidad Nacional de Rosario, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina
| | | | - Diamela Bolzán
- Servicio de Endocrinología del Grupo Gamma, Rosario, Argentina
| | | | | | - Lucas Ricardo Brun
- Laboratorio de Biología Ósea de la Facultad de Ciencias Médicas de la Universidad Nacional de Rosario, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina
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Dutta P, Layton AT. Modeling calcium and magnesium balance: Regulation by calciotropic hormones and adaptations under varying dietary intake. iScience 2024; 27:111077. [PMID: 39493879 PMCID: PMC11530821 DOI: 10.1016/j.isci.2024.111077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 08/21/2024] [Accepted: 09/27/2024] [Indexed: 11/05/2024] Open
Abstract
Magnesium (Mg2+) is crucial for several cellular and physiological processes and is tightly regulated due to health risks associated with imbalances. Mg2+, calcium (Ca2+), parathyroid hormone, and vitamin D3 are tightly coupled, ensuring proper bone metabolism and intestinal and renal absorption of Mg2+ and Ca2+. While several Ca2+ homeostasis models exist, no computational model has been developed to study Mg2+ homeostasis. We developed a computational model of Mg2+ homeostasis in male rats, integrating it with an existing Ca2+ homeostasis model, to understand the interconnected physiological processes regulating their homeostasis. We then analyzed adaptations in these interconnected processes under (1) dietary Mg2+ deficiency, (2) low/high dietary Ca2+ with Mg2+ deficiency, and (3) vitamin D3 deficiency. Model simulations predicted severe hypomagnesemia and mild hypocalcemia with significant dietary Mg2+ deficiency. Low dietary Ca2+ improved, while high dietary Ca2+ worsened Mg2+ deficiency. Finally, vitamin D3 deficiency caused severe hypocalcemia, with minimal impact on Mg2+ homeostasis.
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Affiliation(s)
- Pritha Dutta
- Department of Applied Mathematics, University of Waterloo, Waterloo, ON N2L 3G1, Canada
| | - Anita T. Layton
- Department of Applied Mathematics, University of Waterloo, Waterloo, ON N2L 3G1, Canada
- Department of Biology, University of Waterloo, Waterloo, ON N2L 3G1, Canada
- Cheriton School of Computer Science, University of Waterloo, Waterloo, ON N2L 3G1, Canada
- School of Pharmacology, University of Waterloo, Waterloo, ON N2L 3G1, Canada
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Klett D, Pellissier L, Lomet D, Derouin-Tochon F, Robert V, Nguyen TMD, Duittoz A, Reiter E, Locatelli Y, Dupont J, Dardente H, Jean-Alphonse F, Combarnous Y. Highly-Sensitive In Vitro Bioassays for FSH, TSH, PTH, Kp, and OT in Addition to LH in Mouse Leydig Tumor Cell. Int J Mol Sci 2023; 24:12047. [PMID: 37569429 PMCID: PMC10419024 DOI: 10.3390/ijms241512047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Revised: 07/22/2023] [Accepted: 07/25/2023] [Indexed: 08/13/2023] Open
Abstract
We demonstrate here that highly sensitive in vitro bioassays for FSH, TSH, and PTH can be set up in mouse Leydig Tumor Cells (mLTC), in addition to the normal LH/CG bioassay, after they were transfected with expression vectors encoding the corresponding Gs Protein-Coupled Receptors (GsPCR), such as FSHR, TSHR, or PTHR. Although the β2 adrenergic receptor is also a GsPCR, its expression in mLTC led to a significant but very low cAMP response compared to those observed with FSH, TSH, or PTH. Similarly, after transfection of the GiPCR MT1 melatonin receptor, we did not observe any inhibitory effect by melatonin of the LH or hCG stimulation. Interestingly, after transfection of mLTC with the human kisspeptin receptor (hKpR), which is a GqPCR, we observed a dose-dependent synergy of 10-12-10-7 M kisspeptin variants with a fixed concentration of 0.3 nM LH or hCG. Without any exogenous receptor transfection, a 2 h preincubation with OT or AVP led to a dose-dependent cAMP response to a fixed dose of LH or hCG. Therefore, highly sensitive in vitro bioassays for various hormones and other GPCR ligands can be set up in mLTC to measure circulating concentrations in only 3-10 µL of blood or other body fluids. Nevertheless, the development of an LHRKO mLTC cell line will be mandatory to obtain strict specificity for these bioassays to eliminate potential cross-reaction with LH or CG.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | | | - Yves Combarnous
- INRAe, CNRS, UMR “Physiologie de la Reproduction & des Comportements”, Tours University, Inria, 37380 Nouzilly, France; (D.K.); (L.P.); (D.L.); (T.M.D.N.); (A.D.); (E.R.); (Y.L.); (J.D.); (H.D.); (F.J.-A.)
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Zuo J, Hasan AA, Hocher CF, Kalk P, Kleuser B, Krämer BK, Hocher B. Inverse correlation of intact PTH, oxidized PTH as well as non-oxidized PTH with 25-hydroxyvitamin D3 in kidney transplant recipients. Front Endocrinol (Lausanne) 2023; 14:1178166. [PMID: 37324252 PMCID: PMC10264784 DOI: 10.3389/fendo.2023.1178166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Accepted: 05/17/2023] [Indexed: 06/17/2023] Open
Abstract
Background 25-hydroxyvitamin D (25(OH)D) and potentially also 1,25-dihydroxyvitamin D (1,25(OH)2D) inhibits the synthesis of parathyroid hormone (PTH) in the chief cells of the parathyroid gland. Clinical studies showing a negative correlation between (25(OH)D and PTH are in good agreement with these findings in basic science studies. However, PTH was measured in these studies with the currently clinically used 2nd or 3rd generation intact PTH (iPTH) assay systems. iPTH assays cannot distinguish between oxidized forms of PTH and non-oxidized PTH. Oxidized forms of PTH are the by far most abundant form of PTH in the circulation of patients with impaired kidney function. Oxidation of PTH causes a loss of function of PTH. Given that the clinical studies done so far were performed with an PTH assay systems that mainly detect oxidized forms of PTH, the real relationship between bioactive non-oxidized PTH and 25(OH)D as well as 1,25(OH)2D is still unknown. Methods To address this topic, we compared for the first time the relationship between 25(OH)D as well as 1,25(OH)2D and iPTH, oxPTH as well as fully bioactive n-oxPTH in 531 stable kidney transplant recipients in the central clinical laboratories of the Charité. Samples were assessed either directly (iPTH) or after oxPTH (n-oxPTH) was removed using a column that used anti-human oxPTH monoclonal antibodies, a monoclonal rat/mouse parathyroid hormone antibody (MAB) was immobilized onto a column with 500 liters of plasma samples. Spearman correlation analysis and Multivariate linear regression were used to evaluate the correlations between the variables. Results There was an inverse correlation between 25(OH)D and all forms of PTH, including oxPTH (iPTH: r=-0.197, p<0.0001; oxPTH: r=-0.203, p<0.0001; n-oxPTH: r=-0.146, p=0.001). No significant correlation was observed between 1,25(OH)2D and all forms of PTH. Multiple linear regression analysis considering age, PTH (iPTH, oxPTH and n-oxPTH), serum calcium, serum phosphor, serum creatinine, fibroblast growth factor 23 (FGF23), osteoprotegerin (OPG), albumin, and sclerostin as confounding factors confirmed these findings. Subgroup analysis showed that our results are not affected by sex and age. Conclusion In our study, all forms of PTH are inversely correlated with 25-hydroxyvitamin D (25(OH)D). This finding would be in line with an inhibition of the synthesis of all forms of PTH (bioactive n-oxPTH and oxidized forms of PTH with minor or no bioactivity) in the chief cells of the parathyroid glad.
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Affiliation(s)
- Jiao Zuo
- Department of Nephrology, Charité - Universitätsmedizin Berlin, Berlin, Germany
- Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology, Pneumonology), University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany
| | - Ahmed A. Hasan
- Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology, Pneumonology), University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany
- Institute of Pharmacy, Freie Universität Berlin, Berlin, Germany
| | - Carl-Friedrich Hocher
- Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology, Pneumonology), University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany
- Institute of Pharmacy, Freie Universität Berlin, Berlin, Germany
- Klinik für Innere Medizin, Bundeswehrkrankenhaus Berlin, Berlin, Germany
| | - Philipp Kalk
- Department of Nephrology, Charité - Universitätsmedizin Berlin, Berlin, Germany
- Diaverum Renal Care Center, Diaverum MVZ Am Neuen Garten Standort Ludwigsfelde, Potsdam, Germany
| | - Burkhard Kleuser
- Institute of Pharmacy, Freie Universität Berlin, Berlin, Germany
| | - Bernhard K. Krämer
- Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology, Pneumonology), University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany
- European Center for Angioscience ECAS, Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany
| | - Berthold Hocher
- Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology, Pneumonology), University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany
- Reproductive, Genetic Hospital of CITIC-Xiangya, Changsha, China
- Institute of Medical Diagnostics, IMD, Berlin, Germany
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Zhang R, Huang Q, Su G, Wei M, Cui Y, Zhou H, Song W, Di D, Liu J, Wang Q. Association between multiple vitamins and bone mineral density: a cross-sectional and population-based study in the NHANES from 2005 to 2006. BMC Musculoskelet Disord 2023; 24:113. [PMID: 36765290 PMCID: PMC9912521 DOI: 10.1186/s12891-023-06202-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 01/27/2023] [Indexed: 02/12/2023] Open
Abstract
BACKGROUND Bone mineral density (BMD) alterations in response to multivitamin exposure were rarely studied. Our study assessed the association of coexposure to six types of vitamins (i.e., vitamins B12, B9, C, D, A and E) with BMD measurements in adults in the US. METHODS Data were collected from participants aged ≥ 20 years (n = 2757) in the U.S. National Health and Nutrition Examination Surveys (NHANES) from 2005 to 2006. Multiple linear regression, restricted cubic splines, principal component analysis (PCA) and weighted quantile sum (WQS) regression were performed for statistical analysis. RESULTS The circulating levels of vitamins B12 and C were positively associated with BMDs, and an inverted L-shaped exposure relationship was observed between serum vitamin C and BMDs. PCA identified two principal components: one for 'water-soluble vitamins', including vitamins B12, B9 and C, and one for 'fat-soluble vitamins', including vitamins A, D and E. The former was positively associated with total femur (β = 0.009, 95%CI: 0.004, 0.015) and femoral neck (β = 0.007, 95%CI: 0.002, 0.013) BMDs, and the latter was negatively associated with BMDs with non-statistical significance. The WQS index constructed for the six vitamins was significantly related to total femur (β = 0.010, 95%CI: 0.001, 0.018) and femoral neck (β = 0.008, 95%CI: 0.001, 0.015) BMDs, and vitamins B12 and C weighted the most. The WQS index was inversely related to BMDs with non-statistical significance, and vitamins E and A weighted the most. CONCLUSION Our findings suggested a positive association between water-soluble vitamin coexposure and BMD, and the association was mainly driven by vitamins B12 and C. Negative association between fat-soluble vitamin coexposure and BMD was indicated, mainly driven by vitamins E and A. An inverted L-shaped exposure relationship was found between vitamin C and BMD.
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Affiliation(s)
- Ruyi Zhang
- grid.33199.310000 0004 0368 7223MOE Key Lab of Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 China
| | - Qin Huang
- grid.33199.310000 0004 0368 7223Department of Rehabilitation Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 China
| | - Guanhua Su
- grid.33199.310000 0004 0368 7223Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 China
| | - Muhong Wei
- grid.33199.310000 0004 0368 7223MOE Key Lab of Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 China
| | - Yuan Cui
- grid.33199.310000 0004 0368 7223MOE Key Lab of Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 China
| | - Haolong Zhou
- grid.33199.310000 0004 0368 7223MOE Key Lab of Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 China
| | - Wenjing Song
- grid.33199.310000 0004 0368 7223MOE Key Lab of Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 China
| | - Dongsheng Di
- grid.33199.310000 0004 0368 7223MOE Key Lab of Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 China
| | - Junan Liu
- grid.33199.310000 0004 0368 7223Department of Social Medicine and Health Management, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 China
| | - Qi Wang
- MOE Key Lab of Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
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Yajima A, Tsuchiya K, Kuro-O M, Urena P, Tominaga Y, Okada M, Ichimori T, Tomosugi T, Hiramitsu T, Murata T, Nakamura M, Sasaki M, Ito A, Nitta K. Renal hyperparathyroidism. VITAMINS AND HORMONES 2022; 120:305-343. [PMID: 35953115 DOI: 10.1016/bs.vh.2022.04.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
The number of the patients with chronic kidney disease is now increasing in the world. The pathophysiology of renal hyperparathyroidism is closely associated with Klotho-FGF-endocrine axes, which must be solved definitively as early as possible. It was revealed that the expression of fgf23 is activated by calciprotein particles, which induces vascular ossification. And it is well known that phosphorus overload directly increases parathyroid hormone and hyperparathyroid bone disease develops in those subjects. On the other hand, low turnover bone disease is often recently. Both the patients with chronic kidney disease suffering from hyperparathyroid bone disease or low turnover bone disease are associated with increased fracture risk. Micropetrosis may be one of the causes of increased fracture risk in the subjects with low turnover bone disease. In this chapter, we now describe the diagnosis, pathophysiology and treatments of renal hyperparathyroidism.
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Affiliation(s)
- Aiji Yajima
- Department of Anatomy, Cell Biology and Physiology, Indiana University, School of Medicine, Indianapolis, IN, United States; Department of Urology, Tokyo, Teishin Hospital, Tokyo, Japan; Department Blood Purification, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
| | - Ken Tsuchiya
- Department Blood Purification, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan
| | - Makoto Kuro-O
- Division of Anti-aging Medicine, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Japan
| | - Pablo Urena
- Division of Nephrology, Clinique du Landy, Saint Ouen, France
| | - Yoshihiro Tominaga
- Department of Endocrine Surgery, Nagoya Daini Red Cross Hospital, Nagoya, Japan
| | - Manabu Okada
- Department of Endocrine Surgery, Nagoya Daini Red Cross Hospital, Nagoya, Japan
| | - Toshihiro Ichimori
- Department of Endocrine Surgery, Nagoya Daini Red Cross Hospital, Nagoya, Japan
| | - Toshihide Tomosugi
- Department of Endocrine Surgery, Nagoya Daini Red Cross Hospital, Nagoya, Japan
| | - Takahisa Hiramitsu
- Department of Endocrine Surgery, Nagoya Daini Red Cross Hospital, Nagoya, Japan
| | - Taro Murata
- Department of Urology, Tokyo, Teishin Hospital, Tokyo, Japan
| | - Masaki Nakamura
- Department of Nephrology and Urology, NTT East Kanto Hospital, Tokyo, Japan
| | - Masahiko Sasaki
- Department of Urology, Tokyo, Teishin Hospital, Tokyo, Japan
| | - Akemi Ito
- Ito Bone Histomorphometry Institute, Niigata, Japan
| | - Kosaku Nitta
- Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan
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Nwosu IF, Ibeson CE, Olawoye A, Kyaw H, Kumar K, Odigwe C, Nwosu CA, Oshunsanya A. Interpretation of Parathyroid Hormone Levels in Renal Impairment. Cureus 2022; 14:e25819. [PMID: 35822143 PMCID: PMC9271268 DOI: 10.7759/cureus.25819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/07/2022] [Indexed: 12/02/2022] Open
Abstract
Distinguishing between acute kidney injury and chronic kidney disease (CKD) in an emergency setting may pose a conundrum for physicians, especially when a patient’s medical history and records are unknown. Parathyroid hormone (PTH) has proved valuable as a marker of CKD and is frequently assayed for this reason. The use of PTH as a sole marker of CKD may be misleading in certain conditions, and for this reason, physicians need to interpret PTH values with caution. In patients with no existing medical records, it is vital to consider their overall clinical picture, an accurate interpretation of urinalysis and urine microscopy, and the PTH values when making the initial management decisions.
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Chen X, Chu C, Doebis C, Xiong Y, Cao Y, Krämer BK, von Baehr V, Hocher B. Vitamin D status and its association with parathyroid hormone in 23,134 outpatients. J Steroid Biochem Mol Biol 2022; 220:106101. [PMID: 35351538 DOI: 10.1016/j.jsbmb.2022.106101] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 03/22/2022] [Accepted: 03/24/2022] [Indexed: 12/16/2022]
Abstract
In vitro studies indicate that 25-hydroxyvitamin D3 (25(OH)D3) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) inhibits the synthesis of parathyroid hormone (PTH). The degree of PTH inhibition in humans by circulating 25(OH)D and 1,25(OH)2D may be different. Moreover, age and sex as well as confounding factors like calcium and phosphate may likewise affect the relationship between vitamin D and PTH in humans. However, this was not done so far in adequately powered studies. We investigated the relationship between 25(OH)D as well as 1,25(OH)2D and intact parathyroid hormone (iPTH) in 23,134 outpatients (age mean: 59.81 years) from the Berlin-Brandenburg area of Germany with normal serum creatinine considering confounding factors like age, sex, calcium and phosphate. 25(OH)D and iPTH were inversely correlated (r = -0.17, p < 0.0001). The inverse linear correlation was observed over the entire spectrum of 25(OH)D concentrations - from low 25(OH)D concentrations to very high 25(OH)D concentrations. Multiple linear regression analysis revealed that this correlation was independent of age, sex, creatinine, calcium and phosphate (unstandardized coefficients B: -0.16, p < 0.0001). However, 1,25(OH)2D was only positively associated with iPTH in women (r = 0.05, p = 0.033) and in the subgroup of patients with lower 25(OH)D (25(OH)D< 40 ng/ml) (r = 0.09, p < 0.0001), which was also presented in multiple linear regression analysis (unstandardized coefficients B: 0.20, p = 0.001). Circulating 1,25(OH)2D does not contribute substantially to the regulation of PTH in middle aged and vitamin D sufficient outpatients from the Berlin-Brandenburg area of Germany with normal kidney function. Presumably, serum 25(OH)D that is converted to 1,25(OH)2D after uptake in the parathyroid chief cells plays the critical role.
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Affiliation(s)
- Xin Chen
- Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Germany; Department of Nephrology, Charité - Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany
| | - Chang Chu
- Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Germany; Department of Nephrology, Charité - Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany
| | - Cornelia Doebis
- Institute of Medical Diagnostics, IMD Berlin-Potsdam, Berlin, Germany
| | - Yingquan Xiong
- Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Germany; Department of Nephrology, Charité - Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany
| | - Yaochen Cao
- Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Germany; Department of Nephrology, Charité - Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany
| | - Bernhard K Krämer
- Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Germany
| | - Volker von Baehr
- Institute of Medical Diagnostics, IMD Berlin-Potsdam, Berlin, Germany
| | - Berthold Hocher
- Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Germany; Institute of Medical Diagnostics, IMD Berlin-Potsdam, Berlin, Germany; Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, School of Medicine, Hunan Normal University, Changsha, China; Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, China.
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Ureña Torres PA, Souberbielle JC, Solal MC. Bone Fragility in Chronic Kidney Disease Stage 3 to 5: The Use of Vitamin D Supplementation. Metabolites 2022; 12:metabo12030266. [PMID: 35323709 PMCID: PMC8953916 DOI: 10.3390/metabo12030266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 03/10/2022] [Accepted: 03/17/2022] [Indexed: 12/02/2022] Open
Abstract
Frequently silent until advanced stages, bone fragility associated with chronic kidney disease-mineral and bone disease (CKD-MBD) is one of the most devastating complications of CKD. Its pathophysiology includes the reduction of active vitamin D metabolites, phosphate accumulation, decreased intestinal calcium absorption, renal alpha klotho production, and elevated fibroblast growth factor 23 (FGF23) levels. Altogether, these factors contribute firstly to secondary hyperparathyroidism, and ultimately, to micro- and macrostructural bone changes, which lead to low bone mineral density and an increased risk of fracture. A vitamin D deficiency is common in CKD patients, and low circulating 25(OH)D levels are invariably associated with high serum parathyroid hormone (PTH) levels as well as with bone mineralization defects, such as osteomalacia in case of severe forms. It is also associated with a variety of non-skeletal diseases, including cardiovascular disease, diabetes mellitus, multiple sclerosis, cancer, and reduced immunological response. Current international guidelines recommend supplementing CKD patients with nutritional vitamin D as in the general population; however, there is no randomized clinical trial (RCT) evaluating the effect of vitamin D (or vitamin D+calcium) supplementation on the risk of fracture in the setting of CKD. It is also unknown what level of circulating 25(OH)D would be sufficient to prevent bone abnormalities and fractures in these patients. The impact of vitamin D supplementation on other surrogate endpoints, including bone mineral density and bone-related circulating biomarkers (PTH, FGF23, bone-specific alkaline phosphatase, sclerostin) has been evaluated in several RTCs; however, the results were not always translated into an improvement in long-term outcomes, such as reduced fracture risk. This review provides a brief and comprehensive update on CKD-related bone fragility and the use of natural vitamin D supplementation in these patients.
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Affiliation(s)
- Pablo Antonio Ureña Torres
- Department of Dialysis AURA Nord Saint Ouen, 12, Rue Anselme, 93400 Saint Ouen, France
- Department of Renal Physiology, Necker Hospital, University of Paris Descartes, 75015 Paris, France;
- Correspondence: (P.A.U.T.); (M.C.S.)
| | - Jean Claude Souberbielle
- Department of Renal Physiology, Necker Hospital, University of Paris Descartes, 75015 Paris, France;
| | - Martine Cohen Solal
- Bioscar INSERM U1132, Department of Rheumatology, Université de Paris, Hôpital Lariboisière, 75010 Paris, France
- Correspondence: (P.A.U.T.); (M.C.S.)
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Jørgensen HS, David K, Salam S, Evenepoel P. Traditional and Non-traditional Risk Factors for Osteoporosis in CKD. Calcif Tissue Int 2021; 108:496-511. [PMID: 33586002 DOI: 10.1007/s00223-020-00786-0] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Accepted: 12/02/2020] [Indexed: 12/11/2022]
Abstract
Osteoporosis is a state of bone fragility with reduced skeletal resistance to trauma, and consequently increased risk of fracture. A wide range of conditions, including traditional risk factors, lifestyle choices, diseases and their treatments may contribute to bone fragility. It is therefore not surprising that the multi-morbid patient with chronic kidney disease (CKD) is at a particularly high risk. CKD is associated with reduced bone quantity, as well as impaired bone quality. Bone fragility in CKD is a composite of primary osteoporosis, accumulation of traditional and uremia-related risk factors, assaults brought on by systemic disease, and detrimental effects of drugs. Some risk factors are modifiable and represent potential targets for intervention. This review provides an overview of the heterogeneity of bone fragility in CKD.
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Affiliation(s)
- Hanne Skou Jørgensen
- Nephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Karel David
- Nephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Syazrah Salam
- Sheffield Kidney Institute, Sheffield Teaching Hospitals National Health Service Foundation Trust, Sheffield, UK
- Academic Unit of Bone Metabolism and 3 Mellanby Centre for Bone Research, Medical School, University of Sheffield, Sheffield, UK
| | - Pieter Evenepoel
- Nephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
- Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium.
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11
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Abstract
Introduction Chronic kidney disease (CKD) exposes to an increased incidence of fragility fractures. International guidelines recommend performing bone mineral density (BMD) if the results will impact treatment decisions. It remains unknown where bone loss occurs and what would preclude the longitudinal loss in patients with CKD. Here, we aimed to investigate factors influencing BMD and to analyze the longitudinal BMD changes. Methods In the NephroTest cohort, we measured BMD at the femoral neck, total hip, lumbar spine, and proximal radius, together with circulating biomarkers and standardized measured glomerular filtration rate (mGFR) by 51Cr-EDTA in a subset of patients with CKD stage 1 to 5 followed during 4.3 ± 2.0 years. A linear mixed model explored the longitudinal bone loss and the relationship of associated factors with BMD changes. A total of 858 patients (mean age 58.9 ± 15.2 years) had at least 1 and 477 had at least 2 BMD measures. Results At baseline, cross-sectional analysis showed a significantly lower BMD at femoral neck and total hip and a significant higher serum parathyroid hormone (PTH) along with CKD stages. Baseline age, gender, tobacco, low body mass index (BMI), and high PTH levels were significantly associated with low BMD. Longitudinal analysis during the mean 4.3 years revealed a significant bone loss at the radius only. BMD changes at the femoral neck were associated with BMI, but not CKD stages or basal PTH levels. Conclusions CKD is associated with low BMD and high PTH in the cross-sectional analysis. Longitudinal bone loss occurred at the proximal radius after 4.3 years.
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12
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Ziemińska M, Sieklucka B, Pawlak K. Vitamin K and D Supplementation and Bone Health in Chronic Kidney Disease-Apart or Together? Nutrients 2021; 13:809. [PMID: 33804453 PMCID: PMC7999920 DOI: 10.3390/nu13030809] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 02/15/2021] [Accepted: 02/24/2021] [Indexed: 12/16/2022] Open
Abstract
Vitamin K (VK) and vitamin D (VD) deficiency/insufficiency is a common feature of chronic kidney disease (CKD), leading to impaired bone quality and a higher risk of fractures. CKD patients, with disturbances in VK and VD metabolism, do not have sufficient levels of these vitamins for maintaining normal bone formation and mineralization. So far, there has been no consensus on what serum VK and VD levels can be considered sufficient in this particular population. Moreover, there are no clear guidelines how supplementation of these vitamins should be carried out in the course of CKD. Based on the existing results of preclinical studies and clinical evidence, this review intends to discuss the effect of VK and VD on bone remodeling in CKD. Although the mechanisms of action and the effects of these vitamins on bone are distinct, we try to find evidence for synergy between them in relation to bone metabolism, to answer the question of whether combined supplementation of VK and VD will be more beneficial for bone health in the CKD population than administering each of these vitamins separately.
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Affiliation(s)
- Marta Ziemińska
- Department of Monitored Pharmacotherapy, Medical University of Bialystok, 15-222 Bialystok, Poland;
| | - Beata Sieklucka
- Department of Pharmacodynamics, Medical University of Bialystok, 15-222 Bialystok, Poland;
| | - Krystyna Pawlak
- Department of Monitored Pharmacotherapy, Medical University of Bialystok, 15-222 Bialystok, Poland;
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13
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Lin X, Zhu T, Xu F, Zhong JY, Li F, Shan SK, Wu F, Guo B, Zheng MH, Wang Y, Xu QS, Liao XB, Lu HY, Xie XB, Yuan LQ. Plasma Exosomes Derived From Patients With End-Stage Renal Disease and Renal Transplant Recipients Have Different Effects on Vascular Calcification. Front Cell Dev Biol 2021; 8:618228. [PMID: 33585452 PMCID: PMC7876285 DOI: 10.3389/fcell.2020.618228] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Accepted: 12/18/2020] [Indexed: 01/12/2023] Open
Abstract
End-stage renal disease (ESRD) patients usually develop extensive and progressive vascular calcification, and lots of calcification inhibitors as well as procalcifying factors are involved in the process. However, the mechanisms of vascular calcification in ESRD patients are still ill-defined. In the present study, we found that the plasma exosomes derived from ESRD patients (ESRD-Ex) promoted calcification of vascular smooth muscle cells (VSMCs) significantly, while plasma exosomes from renal transplant recipients (RTR-Ex) could partially attenuate VSMCs calcification. Moreover, the protein concentration of ESRD-Ex was significantly higher than plasma exosomes from the normal health control group (Nor-Ex) and RTR-Ex, and the content of both matrix gla protein (MGP) and Fetuin-A, the calcification inhibitors, were prominently lower in ESRD-Ex than those in Nor-Ex. The content of Annexin-A2, one of the calcification promoters, was significantly higher in ESRD-Ex and RTR-Ex than that in Nor-Ex. However, bone morphogenetic protein (BMP-2) and receptor activator for nuclear factor-κB ligand (Rankl) had no significant difference among the three groups. In addition, the content of Fetuin-A in RTR-Ex was higher than that in ESRD-Ex, although it was still lower than that in Nor-Ex. Furthermore, the levels of both Fetuin-A and MGP in plasma exosomes were negatively while the levels of Annexin-A2 in plasma exosomes was positively correlated to coronary artery calcification scores (CACS). These results indicated that ESRD-Ex significantly promoted VSMCs calcification, while renal transplantation could partially attenuate the procalcification effect of exosomes. Fetuin-A and MGP were decreased, but Annexin-A2 was increased in ESRD-Ex, and renal transplantation could increase the level of Fetuin-A rather than MGP.
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Affiliation(s)
- Xiao Lin
- Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha, China
- Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Ting Zhu
- Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital, Central South University, Changsha, China
- Department of Endocrinology, Central Hospital of Yiyang, Yiyang, China
| | - Feng Xu
- Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Jia-Yu Zhong
- Department of Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Fuxingzi Li
- Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Su-Kang Shan
- Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Feng Wu
- Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Bei Guo
- Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Ming-Hui Zheng
- Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Yi Wang
- Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Qiu-Shuang Xu
- Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Xiao-Bo Liao
- Department of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Hong-Yu Lu
- Xiangya Medical College, Central South University, Changsha, China
| | - Xu-Biao Xie
- Department of Kidney Transplantation, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Ling-Qing Yuan
- Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital, Central South University, Changsha, China
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14
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Tabibzadeh N, Karaboyas A, Robinson BM, Csomor PA, Spiegel DM, Evenepoel P, Jacobson SH, Ureña-Torres PA, Fukagawa M, Al Salmi I, Liang X, Pisoni RL, Young EW. The risk of medically uncontrolled secondary hyperparathyroidism depends on parathyroid hormone levels at haemodialysis initiation. Nephrol Dial Transplant 2021; 36:160-169. [PMID: 33068419 PMCID: PMC7771977 DOI: 10.1093/ndt/gfaa195] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Optimal parathyroid hormone (PTH) control during non-dialysis chronic kidney disease (ND-CKD) might decrease the subsequent risk of parathyroid hyperplasia and uncontrolled secondary hyperparathyroidism (SHPT) on dialysis. However, the evidence for recommending PTH targets and therapeutic strategies is weak for ND-CKD. We evaluated the patient characteristics, treatment patterns and PTH control over the first year of haemodialysis (HD) by PTH prior to HD initiation. METHODS We studied 5683 incident HD patients from 21 countries in Dialysis Outcomes and Practice Patterns Study Phases 4-6 (2009-18). We stratified by PTH measured immediately prior to HD initiation and reported the monthly prescription prevalence of active vitamin D and calcimimetics over the first year of HD and risk of PTH >600 pg/mL after 9-12 months on HD. RESULTS The 16% of patients with PTH >600 pg/mL prior to HD initiation were more likely to be prescribed active vitamin D and calcimimetics during the first year of HD. The prevalence of PTH >600 pg/mL 9-12 months after start of HD was greater for patients who initiated HD with PTH >600 (29%) versus 150-300 (7%) pg/mL (adjusted risk difference: 19%; 95% confidence interval : 15%, 23%). The patients with sustained PTH >600 pg/mL after 9-12 months on HD were younger, more likely to be black, and had higher serum phosphorus and estimated glomerular filtration rates at HD initiation. CONCLUSIONS Increased PTH before HD start predicted a higher PTH level 9-12 months later, despite greater use of active vitamin D and calcimimetics. More targeted PTH control during ND-CKD may influence outcomes during HD, raising the need for PTH target guidelines in these patients.
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Affiliation(s)
- Nahid Tabibzadeh
- Renal Physiology Department, APHP Hôpital Bichat, Université de Paris, INSERM, Paris, France
| | | | - Bruce M Robinson
- Arbor Research Collaborative for Health, Ann Arbor, MI, USA
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | | | - David M Spiegel
- Clinical Development, Relypsa Inc., Vifor Pharma Group Company, Redwood City, CA, USA
| | - Pieter Evenepoel
- Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium
- Department of Microbiology and Immunology, Laboratory of Nephrology, KU Leuven, Leuven, Belgium
| | - Stefan H Jacobson
- Division of Nephrology, Department of Clinical Sciences, Karolinska Institutet, Danderyd University Hospital, Stockholm, Sweden
| | - Pablo-Antonio Ureña-Torres
- Department of Dialysis, AURA Nord Saint Ouen, Saint-Ouen, France
- Department of Renal Physiology, Necker Hospital, University of Paris Descartes, Paris, France
| | - Masafumi Fukagawa
- Division of Nephrology, Endocrinology, and Metabolism, Tokai University School of Medicine, Isehara, Japan
| | - Issa Al Salmi
- Department of Renal Medicine, Royal Hospital, Muscat, Oman
| | - Xinling Liang
- Department of Nephrology, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China
| | | | - Eric W Young
- Arbor Research Collaborative for Health, Ann Arbor, MI, USA
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
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15
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Preka E, Wan M, Price KL, Long DA, Aitkenhead H, Shroff R. Free 25-hydroxyvitamin-D concentrations are lower in children with renal transplant compared with chronic kidney disease. Pediatr Nephrol 2020; 35:1069-1079. [PMID: 31970483 PMCID: PMC7184055 DOI: 10.1007/s00467-020-04472-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Revised: 12/19/2019] [Accepted: 01/02/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Total serum 25-hydroxyvitamin D [25(OH)D] is considered the best marker of vitamin D status and used routinely in clinical practice. However, 25(OH)D is predominantly bound to vitamin D-binding protein (VDBP), and it has been reported that the free-25(OH)D and 25(OH)D loosely bound to albumin fraction correlates better with clinical outcomes. METHODS We assessed total-25(OH)D, measured free-25(OH)D, and calculated free-25(OH)D and their relationship with VDBP and biomarkers of mineral metabolism in 61 children (22 CKD 2-3, 18 dialysis, and 21 post-transplant). RESULTS Total-25(OH)D concentrations were comparable across the three groups (p = 0.09), but free- and bioavailable-25(OH)D (free- and albumin-25(OH)D) were significantly lower in the transplant group (both: p = 0.01). Compared to CKD and dialysis patients, the transplant group had significantly higher VDBP concentrations (p = 0.03). In all three groups, total-25(OH)D concentrations were positively associated with measured free-, calculated free-, and bioavailable-25(OH)D. Multivariable regression analysis showed that total-25(OH)D was the only predictor of measured free-25(OH)D concentrations in the dialysis group (β = 0.9; R2 = 90%). In the transplant group, measured free-25(OH)D concentrations were predicted by both total-25(OH)D and VDBP concentrations (β = 0.6, - 0.6, respectively; R2 = 80%). Correlations between parathyroid hormone with total-25(OH)D and measured and calculated free-25(OH)D were only observed in the transplant group (all: p < 0.001). CONCLUSIONS In transplanted patients, VDBP concentrations were significantly higher compared to CKD and dialysis patients, and consequently, free-25(OH)D concentrations were lower, despite a comparable total-25(OH)D concentration. We suggest that free-25(OH)D measures may be required in children with CKD, dialysis, and transplant, with further research required to understand its association with markers of mineral metabolism.
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Affiliation(s)
- Evgenia Preka
- Renal Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
- Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, London, UK
| | - Mandy Wan
- Renal Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
- Institute of Pharmaceutical Science, King's College London, London, UK.
| | - Karen L Price
- Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, London, UK
| | - David A Long
- Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, London, UK
| | - Helen Aitkenhead
- Department of Chemical Pathology, Great Ormond Street Hospital NHS Foundation Trust, London, UK
| | - Rukshana Shroff
- Renal Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
- Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, London, UK
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16
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Fraser TR, Flogaitis I, Moore AE, Hampson G. The effect of previous treatment with bisphosphonate and renal impairment on the response to denosumab in osteoporosis: a 'real-life' study. J Endocrinol Invest 2020; 43:469-475. [PMID: 31664706 PMCID: PMC7067751 DOI: 10.1007/s40618-019-01131-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Accepted: 10/14/2019] [Indexed: 12/16/2022]
Abstract
PURPOSE To investigate changes in bone mineral density (BMD) following denosumab after previous bisphosphonate therapy and the impact of chronic kidney disease (CKD) on response. METHODS A retrospective study of 134 patients (11 M, 123 F) aged [mean (SD)] 72 [11] years on denosumab was undertaken. Ninety-five patients had previously been on oral and 28 on iv bisphosphonate. Lumbar spine (LS), total hip (TH) and femoral neck (FN) BMD were measured before treatment and at 2.7 [1.2] years. GFR was < 35 ml/min in 24 patients (18%). Ninety-four (18 M, 76 F) patients aged 71 [11] years transitioning to zoledronate were also studied. RESULTS BMD improved following denosumab [mean (SEM) % change LS: 6.0 (0.62) p < 0.001, TH: 2.28 (0.64) p < 0.001, FN: 1.9 (0.77) p = 0.045]. Changes at the TH and FN were lower in patients with GFR < 35 ml/min (Group B) compared to those with GFR > 35 ml/min (Group A) [% change TH; Group A: 2.9 (0.72), Group B: - 0.84 (1.28), p = 0.015, FN; Group A: 2.76 (0.86), Group B: - 1.47 (1.53), p = 0.025]. % change in BMD at the FN and PTH were negatively associated (r = - 0.25, p = 0.013). BMD changes were not different at 12-18 months between patients on denosumab compared to zoledronate [% change at LS: denosumab: 3.97% (0.85), zoledronate: 2.6% (0.5), p = 0.19 TH: denosumab: 0.97% (0.58), zoledronate: 0.92% (0.6), p = 0.95). CONCLUSION Denosumab increases BMD following previous bisphosphonate treatment and is comparable to zoledronate. Lower response seen at the hip in CKD is related to PTH concentrations.
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Affiliation(s)
- T R Fraser
- Department of Chemical Pathology and Metabolic Medicine, St Thomas' Hospital, Lambeth Palace Road, London, SE1 7EH, UK
- Osteoporosis Unit, Guy's Hospital, London, SE1 9RT, UK
| | - I Flogaitis
- Department of Chemical Pathology and Metabolic Medicine, St Thomas' Hospital, Lambeth Palace Road, London, SE1 7EH, UK
- Osteoporosis Unit, Guy's Hospital, London, SE1 9RT, UK
| | - A E Moore
- Osteoporosis Unit, Guy's Hospital, London, SE1 9RT, UK
| | - G Hampson
- Department of Chemical Pathology and Metabolic Medicine, St Thomas' Hospital, Lambeth Palace Road, London, SE1 7EH, UK.
- Metabolic Bone Clinic, Department of Rheumatology, Guy's Hospital, London, UK.
- Osteoporosis Unit, Guy's Hospital, London, SE1 9RT, UK.
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Liabeuf S, McCullough K, Young EW, Pisoni R, Zee J, Reichel H, Pecoits-Filho R, Port FK, Stengel B, Csomor PA, Metzger M, Robinson B, Massy ZA. International variation in the management of mineral bone disorder in patients with chronic kidney disease: Results from CKDopps. Bone 2019; 129:115058. [PMID: 31493530 DOI: 10.1016/j.bone.2019.115058] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Revised: 08/12/2019] [Accepted: 09/03/2019] [Indexed: 11/29/2022]
Abstract
BACKGROUND AND OBJECTIVES Chronic kidney disease (CKD) is commonly associated with mineral and bone metabolism disorders, but these are less frequently studied in non-dialysis CKD patients than in dialysis patients. We examined and described international variation in mineral and bone disease (MBD) markers and their treatment and target levels in Stage 3-5 CKD patients. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS Prospective cohort study of 7658 adult patients with eGFR <60mL/min/1.73m2, excluding dialysis or transplant patients, participating in the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps) in Brazil, France, Germany, and the US. CKD-MBD laboratory markers included serum levels of phosphorus (P), calcium (Ca), intact parathyroid hormone (iPTH), and 25-hydroxyvitamin D (25-D). MBD treatment data included phosphate binders and vitamin D (nutritional and active). Nephrologist survey data were collected on target MBD marker levels. RESULTS Over two-thirds of the patients had MBD markers measured at time intervals in line with practice guidelines. P and iPTH increased and Ca decreased gradually from eGFR 60-20mL/min/1.73m2 and more sharply for eGFR<20. 25-D showed no relation to eGFR. Nephrologist survey data indicated marked variation in upper target P and iPTH levels. Among patients with P>5.5mg/dL, phosphate binder use was 14% to 43% across the four countries. Among patients with PTH >300pg/mL, use of active (calcitriol and related analogs) vitamin D was 12%-51%, and use of any (active or nutritional) vitamin D was 60%-87%. CONCLUSIONS Although monitoring of CKD-MBD laboratory markers by nephrologists in CKDopps countries is consistent with guidelines, target levels vary notably and prescription of medications to treat abnormalities in these laboratory markers is generally low in these cross-sectional analyses. While there are opportunities to increase treatment of hyperphosphatemia, hyperparathyroidism, and vitamin D deficiency in advanced CKD, the effect on longer-term complications of these conditions requires study.
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Affiliation(s)
- Sophie Liabeuf
- Pharmacology Department and Laboratory EA 7517, Amiens University Hospital, 80000 Amiens, France
| | | | - Eric W Young
- Arbor Research Collaborative for Health, Ann Arbor, MI, USA
| | - Ronald Pisoni
- Arbor Research Collaborative for Health, Ann Arbor, MI, USA
| | - Jarcy Zee
- Arbor Research Collaborative for Health, Ann Arbor, MI, USA
| | | | - Roberto Pecoits-Filho
- Arbor Research Collaborative for Health, Ann Arbor, MI, USA; Pontifícia Universidade Católica Do Paraná, Nephrology, Do Paraná, Brazil
| | | | - Bénédicte Stengel
- Centre for Research in Epidemiology and Population Health (CESP), UMRS 1018, UVSQ, University Paris-Saclay, Villejuif, France
| | | | - Marie Metzger
- Centre for Research in Epidemiology and Population Health (CESP), UMRS 1018, UVSQ, University Paris-Saclay, Villejuif, France
| | - Bruce Robinson
- Arbor Research Collaborative for Health, Ann Arbor, MI, USA
| | - Ziad A Massy
- Centre for Research in Epidemiology and Population Health (CESP), UMRS 1018, UVSQ, University Paris-Saclay, Villejuif, France; Department of Nephrology, Ambroise Paré University Hospital, APHP, Boulogne Billancourt/Paris, France.
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18
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Yalla N, Bobba G, Guo G, Stankiewicz A, Ostlund R. Parathyroid hormone reference ranges in healthy individuals classified by vitamin D status. J Endocrinol Invest 2019; 42:1353-1360. [PMID: 31273631 PMCID: PMC6790182 DOI: 10.1007/s40618-019-01075-w] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2018] [Accepted: 06/11/2019] [Indexed: 12/19/2022]
Abstract
PURPOSE Parathyroid hormone (PTH) concentrations are routinely measured in the diagnosis and management of bone and kidney diseases, but reference ranges can be overestimated if determined in otherwise healthy individuals for whom vitamin D deficiency was not evaluated. We establish PTH reference ranges in apparently healthy, normocalcemic, normophosphatemic individuals categorized by 25-hydroxyvitamin D (25(OH)D) status using the Elecsys® PTH (cobas e 601) and Elecsys® Vitamin D total II electrochemiluminescence immunoassays (cobas e 411). METHODS This prospective, non-interventional study measured PTH in serum from 653 apparently healthy adults [56.7% female; 68.2% white/Caucasian; 28.6% African American; median age 44 years (range 21-83)] from three diverse geographic sites across the USA during summer and winter months. Subjects were classified by concomitant vitamin D sufficiency (≥ 30 ng/mL), insufficiency (> 20 to < 30 ng/mL) or deficiency (≤ 20 ng/mL). RESULTS In vitamin D sufficiency, median PTH was 31.9 pg/mL [range (2.5th-97.5th percentile) 17.9-58.6] compared with 35.5 pg/mL (17.0-60.4) for insufficiency, and 39.8 pg/mL (19.5-86.4) for deficiency. A significant inverse relationship was found between PTH and 25(OH)D (P < 0.001). After accounting for vitamin D, potential effects of race or season as covariates were relatively small or absent. CONCLUSIONS Upper reference limits (URL) for PTH in vitamin D sufficiency/insufficiency were similar and lower than current values. Clinically important PTH elevations were observed in vitamin D deficiency, where revised reference ranges with a higher URL may be appropriate. These data may help to distinguish vitamin D-related PTH elevations from other causes [e.g., primary (normocalcemic) or secondary hyperparathyroidism].
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Affiliation(s)
- N Yalla
- Washington University, St. Louis, MO, USA
| | - G Bobba
- Roche Diagnostics International Ltd, Rotkreuz, Switzerland
| | - G Guo
- Roche Diagnostics Inc., Indianapolis, IN, USA
| | | | - R Ostlund
- Washington University, St. Louis, MO, USA.
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19
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Olvera-Soto MG, Ruiz Medina VL, Medeiros M, Castillo-Martínez L, López-López CO, Fuchs-Tarlovsky V, Monroy A, Valdez-Ortiz R. Effect of Resistance Exercise Plus Cholecalciferol on Nutritional Status Indicators in Adults With Stage 4 Chronic Kidney Disease. J Ren Nutr 2019; 30:232-241. [PMID: 31597621 DOI: 10.1053/j.jrn.2019.07.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2019] [Revised: 07/22/2019] [Accepted: 07/28/2019] [Indexed: 12/17/2022] Open
Abstract
OBJECTIVE Decreased serum concentrations of 25-hydroxyvitamin D (25(OH)D) affect people with chronic kidney disease (CKD); lower concentrations of 25(OH)D have been associated with decrease in nutritional status indicators. On the other hand, muscle resistance exercise has improved the nutritional status of patients with CKD.The aim of this study was to evaluate the effect of resistance exercise and dietary supplementation with cholecalciferol on nutritional status indicators in adults with stage 4 CKD. METHODS Patients with an estimated glomerular filtration rate between 15 and 29 mL/min/1.73 m2 in an open-label clinical trial were followed for 12 weeks. The intervention group received exercise resistance training sessions three times per week with oral cholecalciferol supplementation each day. The control group only received standard medical care. The outcomes were anthropometric measurements, handgrip strength, and bioelectrical impedance analysis. RESULTS Thirty-nine patients of a median age of 48 (36-52) years had an estimated glomerular filtration rate of 21.8 ± 6.5 mL/min/1.73 m2. A total of 57.5% of the patients were women. In 41% of the patients, the etiology of CKD was diabetes. After 12 weeks, in the intervention group, the adherence to the resistance training was 77%, and the adherence to the supplementation with cholecalciferol was 96.2%. Significant improvements in 25(OH)D serum concentrations and in handgrip strength were detected in the intervention group (P < .05). In the control group, a decrease in 25(OH)D serum concentrations and a loss in handgrip strength were observed, although the difference was not statistically significant. Anthropometrics and biochemical and dietary indicators, but not bioelectrical impedance data, exhibited changes. CONCLUSION Supplementation with cholecalciferol improves serum concentrations of 25(OH)D and, when combined with resistance exercise, improved muscle function as measured by handgrip strength in a study of patients with CKD not on dialysis.
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Affiliation(s)
- Ma Guadalupe Olvera-Soto
- Doctorate Program in Health Sciences, Universidad Nacional Autónoma de México, México City, México; Department of Nephrology, Hospital General de México, Dr. Eduardo Liceaga, México City, México.
| | | | - Mara Medeiros
- Nephrology Research Laboratory, Department of Pediatric Nephrology, Hospital Infantil de México Federico Gómez, México City, DF, Mexico
| | - Lilia Castillo-Martínez
- Clinical Nutrition Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | | | - Adriana Monroy
- Department of Oncology, Hospital General de México, México City, México
| | - Rafael Valdez-Ortiz
- Department of Nephrology, Hospital General de México, Dr. Eduardo Liceaga, México City, México.
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Pimentel A, Ureña-Torres P, Zillikens MC, Bover J, Cohen-Solal M. Fractures in patients with CKD—diagnosis, treatment, and prevention: a review by members of the European Calcified Tissue Society and the European Renal Association of Nephrology Dialysis and Transplantation. Kidney Int 2017; 92:1343-1355. [DOI: 10.1016/j.kint.2017.07.021] [Citation(s) in RCA: 110] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2017] [Revised: 07/12/2017] [Accepted: 07/17/2017] [Indexed: 01/29/2023]
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Molina P, Carrero JJ, Bover J, Chauveau P, Mazzaferro S, Torres PU, for the European Renal Nutrition (ERN) and Chronic Kidney Disease‐Mineral and Bone Disorder (CKD‐MBD) Working Groups of the European Renal Association–European Dialysis Transplant Association (ERA‐EDTA). Vitamin D, a modulator of musculoskeletal health in chronic kidney disease. J Cachexia Sarcopenia Muscle 2017; 8:686-701. [PMID: 28675610 PMCID: PMC5659055 DOI: 10.1002/jcsm.12218] [Citation(s) in RCA: 81] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2016] [Revised: 04/04/2017] [Accepted: 04/20/2017] [Indexed: 02/06/2023] Open
Abstract
The spectrum of activity of vitamin D goes beyond calcium and bone homeostasis, and growing evidence suggests that vitamin D contributes to maintain musculoskeletal health in healthy subjects as well as in patients with chronic kidney disease (CKD), who display the combination of bone metabolism disorder, muscle wasting, and weakness. Here, we review how vitamin D represents a pathway in which bone and muscle may interact. In vitro studies have confirmed that the vitamin D receptor is present on muscle, describing the mechanisms whereby vitamin D directly affects skeletal muscle. These include genomic and non-genomic (rapid) effects, regulating cellular differentiation and proliferation. Observational studies have shown that circulating 25-hydroxyvitamin D levels correlate with the clinical symptoms and muscle morphological changes observed in CKD patients. Vitamin D deficiency has been linked to low bone formation rate and bone mineral density, with an increased risk of skeletal fractures. The impact of low vitamin D status on skeletal muscle may also affect muscle metabolic pathways, including its sensitivity to insulin. Although some interventional studies have shown that vitamin D may improve physical performance and protect against the development of histological and radiological signs of hyperparathyroidism, evidence is still insufficient to draw definitive conclusions.
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Affiliation(s)
- Pablo Molina
- Department of NephrologyHospital Universitario Doctor PesetValenciaSpain
- REDinRENMadridSpain
- Department of MedicineUniversitat de ValènciaValenciaSpain
| | - Juan J. Carrero
- Division of Renal MedicineCLINTEC, Karolinska InstitutetStockholmSweden
| | - Jordi Bover
- REDinRENMadridSpain
- Department of NephrologyFundació PuigvertBarcelonaSpain
- IIB Sant PauBarcelonaSpain
| | - Philippe Chauveau
- Service de Néphrologie Transplantation DialyseCentre Hospitalier Universitaire de Bordeaux et Aurad‐AquitaineBordeauxFrance
| | - Sandro Mazzaferro
- Department of Cardiovascular, Respiratory, Nephrologic and Geriatric SciencesSapienza University of RomeRomeItaly
| | - Pablo Ureña Torres
- Department of Nephrology and DialysisClinique du Landy, Ramsay‐Générale de SantéSaint OuenParisFrance
- Department of Renal PhysiologyNecker Hospital, University of Paris DescartesParisFrance
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Messa P, Regalia A, Alfieri CM. Nutritional Vitamin D in Renal Transplant Patients: Speculations and Reality. Nutrients 2017; 9:nu9060550. [PMID: 28554998 PMCID: PMC5490529 DOI: 10.3390/nu9060550] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2017] [Revised: 05/15/2017] [Accepted: 05/22/2017] [Indexed: 12/14/2022] Open
Abstract
Reduced levels of nutritional vitamin D are commonly observed in most chronic kidney disease (CKD) patients and particularly in patients who have received a kidney transplant (KTx). In the complex clinical scenario characterizing the recipients of a renal graft, nutritional vitamin D deficiency has been put in relation not only to the changes of mineral and bone metabolism (MBM) after KTx, but also to most of the medical complications which burden KTx patients. In fact, referring to its alleged pleiotropic (non-MBM related) activities, vitamin D has been claimed to play some role in the occurrence of cardiovascular, metabolic, immunologic, neoplastic and infectious complications commonly observed in KTx recipients. Furthermore, low nutritional vitamin D levels have also been connected with graft dysfunction occurrence and progression. In this review, we will discuss the purported and the demonstrated effects of native vitamin D deficiency/insufficiency in most of the above mentioned fields, dealing separately with the MBM-related and the pleiotropic effects.
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Affiliation(s)
- Piergiorgio Messa
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano 20122, Italy.
- via Festa del Perdono, Università degli Studi di Milano, Milano 20122, Italy.
| | - Anna Regalia
- via Festa del Perdono, Università degli Studi di Milano, Milano 20122, Italy.
| | - Carlo Maria Alfieri
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano 20122, Italy.
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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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Zheng JQ, Hou YC, Zheng CM, Lu CL, Liu WC, Wu CC, Huang MT, Lin YF, Lu KC. Cholecalciferol Additively Reduces Serum Parathyroid Hormone and Increases Vitamin D and Cathelicidin Levels in Paricalcitol-Treated Secondary Hyperparathyroid Hemodialysis Patients. Nutrients 2016; 8:708. [PMID: 27827962 PMCID: PMC5133095 DOI: 10.3390/nu8110708] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2016] [Revised: 10/10/2016] [Accepted: 11/01/2016] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Active Vitamin D analogues are used clinically for prevention and treatment of secondary hyperparathyroidism (SHPT) in hemodialysis (HD) patients. Nutritional vitamin D supplementation is used for additional local parathyroid (PTH) suppression, with lower incidence of hypercalcemia and hyperphosphatemia. This study evaluates the possible beneficial effects of combined vitamin D treatment (paricalcitol and cholecalciferol). METHODS Sixty HD patients with serum parathyroid hormone (iPTH) >300 pg/mL were enrolled. All patients administered 2 mcg/day of paricalcitol and were randomly allocated into control group (placebo) or study group (cholecalciferol) for 16 weeks. Serum 25(OH)D₃, iPTH and human cathelicidin (hCAP-18) were measured at baseline and during follow-up. RESULTS iPTH levels decreased in the study group appropriately and were more significantly decreased at 16 weeks. Study group had significantly increased 25(OH)D₃ levels. In addition, the study group had significantly increased serum hCAP-18 levels compared with control group. Correlation analysis showed a significant correlation between the percentage increase in serum hCAP-18 and 25(OH)D₃ levels. CONCLUSIONS Cholecalciferol, in combination with paricalcitol, additively lowers the iPTH levels in a significant number of patients after 16 weeks of supplementation. A dose of 5000 IU/week of cholecalciferol could maintain serum 25(OH)D₃ levels above 30 ng/dL as early as 8 weeks after beginning supplementation. Doubling of serum cathelicidin levels were noted after 16 weeks of cholecalciferol supplementation in 40% of study patients.
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Affiliation(s)
- Jing-Quan Zheng
- Division of Critical Care Medicine, Department of Emergency Medicine-Critical Care Medicine (EM-CCM), Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan.
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
| | - Yi-Chou Hou
- Division of Nephrology, Department of Internal Medicine, Cardinal Tien Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City 23148, Taiwan.
| | - Cai-Mei Zheng
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
- Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
- Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan.
| | - Chien-Lin Lu
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
| | - Wen-Chih Liu
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
- Division of Nephrology, Department of Internal Medicine, Cardinal Tien Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City 23148, Taiwan.
| | - Chia-Chao Wu
- Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan.
| | - Ming-Te Huang
- Division of Critical Care Medicine, Department of Emergency Medicine-Critical Care Medicine (EM-CCM), Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan.
- Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan.
| | - Yuh-Feng Lin
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
- Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
- Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan.
| | - Kuo-Cheng Lu
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
- Division of Nephrology, Department of Internal Medicine, Cardinal Tien Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City 23148, Taiwan.
- Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan.
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Li M, Lv F, Zhang Z, Deng W, Li Y, Deng Z, Jiang Y, Wang O, Xing X, Xu L, Xia W. Establishment of a normal reference value of parathyroid hormone in a large healthy Chinese population and evaluation of its relation to bone turnover and bone mineral density. Osteoporos Int 2016; 27:1907-16. [PMID: 26733373 DOI: 10.1007/s00198-015-3475-5] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2015] [Accepted: 12/21/2015] [Indexed: 01/06/2023]
Abstract
UNLABELLED A normal reference value of parathyroid hormone (PTH) was established for the first time in a large sample of healthy Chinese subjects by completely excluding interference of vitamin D deficiency. A high PTH level correlated significantly with an elevated bone turnover and a reduced bone mineral density (BMD). INTRODUCTION The aims of this study are to establish a normal reference value for serum PTH and to evaluate the effect of parathyroid gland status on bone turnover and BMD. METHODS Our cross-sectional study included 1436 healthy individuals from 5 different Chinese cities. Concentrations of serum PTH, 25-hydroxyvitamin D (25OHD), procollagen I N-terminal peptide (P1NP, a bone formation marker), and carboxyl-terminal telopeptide of type I collagen (β-CTX, a bone resorption marker) were measured by electrochemiluminescence immunoassay. BMD was measured by dual-energy X-ray absorptiometry. The relation of PTH concentration to age, gender, height, and weight was examined. Reference values of PTH were established for all subjects and for subjects categorized by serum 25OHD concentrations. Correlations of PTH levels with bone turnover biomarkers and BMD were statistically analyzed. RESULTS Reference values of PTH were 8.84-69.95 pg/mL in all the subjects and 7.48-60.73 and 5.83-56.78 pg/mL in the subjects with serum 25OHD concentrations of ≥20 and ≥30 ng/mL, respectively. Serum PTH showed a negative linear correlation with 25OHD, and the breakpoint was 18.21 ng/mL, below which the PTH level rapidly increased. The increase in PTH levels with age showed a positive linear correlation with P1NP and β-CTX concentrations and a negative linear correlation with BMD at the lumbar spines and the femoral neck. CONCLUSIONS A reference value of PTH was established in a large sample of healthy Chinese subjects according to 25OHD status, gender, and age. A high PTH level correlated significantly with an elevated bone turnover and a reduced BMD.
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Affiliation(s)
- M Li
- Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, 100730, China
| | - F Lv
- Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, 100730, China
| | - Z Zhang
- Department of Osteoporosis, Sixth People's Hospital, Shanghai Jiaotong University, No. 600 Yishan Road, Shanghai, 200233, China
| | - W Deng
- Department of Geriatrics, General Hospital of Guangzhou Military Command, No. 111 Liuhua Road, Guangzhou, 510010, China
| | - Y Li
- Department of Laboratory, Hubei General Hospital, No. 238 Jiefang Road, Wuhan, 430060, China
| | - Z Deng
- Department of Orthopedics, The Second Affiliated Hospital of Chongqing Medical University, No. 76 Linjiang road, Chongqing, 400010, China
| | - Y Jiang
- Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, 100730, China
| | - O Wang
- Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, 100730, China
| | - X Xing
- Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, 100730, China
| | - L Xu
- Department of Obstetrics and Gynecology, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, 100730, China
| | - W Xia
- Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, 100730, China.
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Park JH, Park HK, Jung H, Lee SS, Koo HK. Parathyroid Hormone as a Novel Biomarker for Chronic Obstructive Pulmonary Disease: Korean National Health and Nutrition Examination Survey. PLoS One 2015; 10:e0138482. [PMID: 26398210 PMCID: PMC4580427 DOI: 10.1371/journal.pone.0138482] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2015] [Accepted: 08/31/2015] [Indexed: 11/19/2022] Open
Abstract
Objective To understand and predict chronic obstructive pulmonary disease (COPD), a biomarker that reflects disease severity is needed. Research Design and Methods Data from 10269 adults aged over 40 years of age were retrieved from the Korea National Health and Nutrition Examination Survey (KNHANES), and 1302 patients met the criteria for COPD. The association between values of vitamin D and parathyroid hormone (PTH), and COPD severity including lung function and quality of life, were analyzed. Results In COPD patients, lung function was inversely related to PTH values (P = 0.02 for FVC [% predicted]; P < 0.001 for FEV1 [% predicted]); however, the association of lung function with vitamin D levels was not statistically significant in a multivariable analysis. Value of PTH was independently associated with EQ5D-index (P = 0.04), but vitamin D level showed no significant relationship with EQ5D-index (P = 0.59) or EQ5D-VAS (P = 0.81). Conclusions Elevation of PTH, unlike vitamin D, is independently associated with COPD severity, and may be a better biomarker for COPD.
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Affiliation(s)
- Joo-Hyun Park
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Ilsan Paik Hospital, Inje University college of Medicine, Goyang, Korea
| | - Hye Kyeong Park
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Ilsan Paik Hospital, Inje University college of Medicine, Goyang, Korea
| | - Hoon Jung
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Ilsan Paik Hospital, Inje University college of Medicine, Goyang, Korea
| | - Sung-Soon Lee
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Ilsan Paik Hospital, Inje University college of Medicine, Goyang, Korea
| | - Hyeon-Kyoung Koo
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Ilsan Paik Hospital, Inje University college of Medicine, Goyang, Korea
- * E-mail:
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Rodríguez M, Rodríguez-Ortiz ME. Advances in pharmacotherapy for secondary hyperparathyroidism. Expert Opin Pharmacother 2015; 16:1703-16. [DOI: 10.1517/14656566.2015.1061994] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Maeda SS, Borba VZC, Camargo MBR, Silva DMW, Borges JLC, Bandeira F, Lazaretti-Castro M. Recommendations of the Brazilian Society of Endocrinology and Metabology (SBEM) for the diagnosis and treatment of hypovitaminosis D. ACTA ACUST UNITED AC 2015; 58:411-33. [PMID: 25166032 DOI: 10.1590/0004-2730000003388] [Citation(s) in RCA: 131] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2014] [Accepted: 06/18/2014] [Indexed: 12/14/2022]
Abstract
OBJECTIVE The objective is to present an update on the diagnosis and treatment of hypovitaminosis D, based on the most recent scientific evidence. MATERIALS AND METHODS The Department of Bone and Mineral Metabolism of the Brazilian Society of Endocrinology and Metabology (SBEM) was invited to generate a document following the rules of the Brazilian Medical Association (AMB) Guidelines Program. Data search was performed using PubMed, Lilacs and SciELO and the evidence was classified in recommendation levels, according to the scientific strength and study type. CONCLUSION A scientific update regarding hypovitaminosis D was presented to serve as the basis for the diagnosis and treatment of this condition in Brazil.
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Affiliation(s)
- Sergio Setsuo Maeda
- Disciplina de Endocrinologia, Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, SP, Brasil
| | - Victoria Z C Borba
- Departamento de Clínica Médica, Universidade Federal do Paraná, Curitiba, PR, Brasil
| | | | | | | | - Francisco Bandeira
- Disciplina de Endocrinologia, Hospital Agamenon Magalhães, Escola de Medicina, Universidade de Pernambuco, Recife, PE, Brasil
| | - Marise Lazaretti-Castro
- Disciplina de Endocrinologia, Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, SP, Brasil
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Damasiewicz MJ, Toussaint ND. Is nutritional vitamin D supplementation beneficial in dialysis patients? Clin J Am Soc Nephrol 2015; 10:544-6. [PMID: 25770174 DOI: 10.2215/cjn.01780215] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Affiliation(s)
- Matthew J Damasiewicz
- Departments of Nephrology and Medicine, Monash Medical Centre, Clayton, Victoria, Australia
| | - Nigel D Toussaint
- Department of Nephrology, Royal Melbourne Hospital, Parkville, Victoria, Australia; and Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
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Vitamin A intake, serum vitamin D and bone mineral density: analysis of the Korea National Health and Nutrition Examination Survey (KNHANES, 2008-2011). Nutrients 2015; 7:1716-27. [PMID: 25763530 PMCID: PMC4377877 DOI: 10.3390/nu7031716] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2014] [Revised: 02/26/2015] [Accepted: 02/27/2015] [Indexed: 01/01/2023] Open
Abstract
The association of high vitamin A intake and low bone mineral density (BMD) is still controversial. To determine the association of dietary vitamin A intake and serum 25-hydroxyvitamin D (25(OH)D) concentration with BMD, a total of 6481 subjects (2907 men and 3574 women) aged ≥50 years from the Korean National Health and Nutrition Examination Survey (2008–2011) were divided into groups according to dietary vitamin A intake (tertiles) and serum 25(OH)D (<50, 50–75, >75 nmol/L), and evaluated for BMD after adjusting for relevant variables. Mean dietary vitamin A intakes were 737 and 600 μg RE (Retinol Equivalents) in men and women, respectively. Total hip and femoral neck BMD in men and lumbar spine BMD in women were both positively correlated with dietary vitamin A intake in subjects with serum 25(OH)D >75 nmol/L. Among men with serum 25(OH)D <50 nmol/L, both the top (mean 1353 μg RE) and bottom (mean 218 μg RE) tertiles of dietary vitamin A intake had lower BMD than the middle group (mean 577 μg RE). In this population, BMD was the highest among men and women with serum 25(OH)D = 50–75 nmol/L and that there were no differences in BMD by vitamin A intake in these vitamin D adequate groups. This cross-sectional study indicates that vitamin A intake does not affect bone mineral density as long as the serum 25(OH)D concentration is maintained in the moderate level of 50–75 nmol/L.
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Delanaye P, Bouquegneau A, Krzesinski JM, Cavalier É, Jean G, Urena-Torres P, Souberbielle JC. [Native vitamin D in dialysis patients]. Nephrol Ther 2015; 11:5-15. [PMID: 25597001 DOI: 10.1016/j.nephro.2014.10.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2014] [Revised: 10/14/2014] [Accepted: 10/14/2014] [Indexed: 12/18/2022]
Abstract
Chronic kidney disease is frequent and usually responsible of mineral and bone disorder. These abnormalities lead to increased morbidity and mortality. To become active, native vitamin D needs a first hydroxylation in the liver, and a second one in the kidney. Next to its action on bone metabolism, vitamin D also possesses pleiotropic actions on cardiovascular, immune and neurological systems as well as antineoplastic activities. End-stage renal disease (ESRD) is also associated with a decrease in vitamin D activity by mechanisms including the increase of plasma phosphate concentration, secretion of FGF-23 and decrease in 1α-hydroxylase activity. The prevalence of 25 hydroxy-vitamin D deficiency depends on the chosen cut-off value to define this lack. Currently it is well established that a patient has to be substituted when 25 hydroxy-vitamin D level is under 30 ng/mL. The use and monitoring of 1.25 hydroxy-vitamin D is still not recommended in routine practice. The goals of vitamin D treatment in case of ESRD are to substitute the deficiency and to prevent or treat hyperparathyroidism. Interest of native vitamin D in first intention is now well demonstrated. This review article describes the vitamin D metabolism and physiology and also the treatment for vitamin D deficiency in ESRD population.
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Affiliation(s)
- Pierre Delanaye
- Service de néphrologie-dialyse, CHU Sart-Tilman, université de Liège, 4000 Liège, Belgique.
| | - Antoine Bouquegneau
- Service de néphrologie-dialyse, CHU Sart-Tilman, université de Liège, 4000 Liège, Belgique
| | - Jean-Marie Krzesinski
- Service de néphrologie-dialyse, CHU Sart-Tilman, université de Liège, 4000 Liège, Belgique
| | - Étienne Cavalier
- Service de chimie clinique, CHU Sart-Tilman, université de Liège, 4000 Liège, Belgique
| | - Guillaume Jean
- Néphrologie et dialyse, Nephrocare Tassin-Charcot, Sainte-Foy-les-Lyon, France
| | - Pablo Urena-Torres
- Laboratoire d'explorations fonctionnelles, Inserm U845, hôpital Necker-Enfants malades, Paris, France; Service de néphrologie et dialyse, clinique du Landy, Saint-Ouen, France
| | - Jean-Claude Souberbielle
- Laboratoire d'explorations fonctionnelles, Inserm U845, hôpital Necker-Enfants malades, Paris, France
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Zhang J, Zhang P, Ni X, Bao B, Huang C, Wu Y, Ni M, Duan J, Chen J. Vitamin D status in chronic dialysis patients with depression: a prospective study. BMC Psychiatry 2014; 14:125. [PMID: 24774860 PMCID: PMC4014207 DOI: 10.1186/1471-244x-14-125] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2014] [Accepted: 04/22/2014] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Depression is the most widely acknowledged psychological problem among end-stage renal disease (ESRD) patients. Depression may be associated with VD deficiency. The aims of this study are to (a) elucidate the prospective association between HsCRP, VD contents and depressive symptoms in the dialyzed population, and (b) find the effect of calcitriol supplementation on depression in dialyzed patients. METHODS In this prospective study, 484 dialysis patients (382 hemodialysis [HD] cases and 102 peritoneal dialysis [PD] cases; aged 18-60 years) from two hospitals in southeast China were included. The depression in these patients was evaluated using the Chinese version of Beck's Depression Inventory (BDI). All subjects answered the BDI-I questionnaire for assessment of depression levels in summer. A cut-off value of 16 was set to include dialysis patients with depression. All patients were divided into two groups depending on the absence (Group 1) or presence (Group 2) of depression. The two groups took 0.5 μg/day 1,25-Dihydroxyvitamin D orally for one year. BDI Scores were recalculated for all patients. Sociodemographic, clinical data, and serum VD contents were also collected. RESULTS A total of 484 participants (247 men [51.0%] and 237 women [49.0%]) were surveyed. Depressive symptoms were found in 213 (44.0%) patients. The baseline serum VD level (VD2 + VD3) was 17.6 ± 7.7 nmol/L. Patients with depressive symptoms have significantly higher serum HsCRP level and significantly lower serum VD level compared with the control group. After one-year follow-up, the supplementation of 0.5 μg/day calcitriol slightly improved the microinflammatory state such as lowering mean serum HsCRP level and improving serum VD level, but not in significantly enhancing the depressive symptoms. CONCLUSIONS Calcitriol supplementation did not significantly enhance the depressive symptoms in our dialyzed population although patients with low levels of serum VD were more depressed. Therefore, more prospective randomized controlled trials are necessary to reveal the exact cause-and-effect relationship between VD status and depressive symptoms or VD status related to some specific subtypes in dialyzed patients.
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Affiliation(s)
- Jisheng Zhang
- Department of Nephrology, Beilun Branch of the First Affiliated Hospital, College of Medicine, Zhejiang University, Ningbo, Zhejiang, PR China.
| | - Ping Zhang
- Department of Nephrology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China
| | - Xiaoying Ni
- Department of Neurology, People's Hospital of Yinzhou, College of Medicine, Ningbo University, Ningbo, Zhejiang, PR China
| | - Beiyan Bao
- Department of Nephrology, Ningbo Urology and Nephrology Hospital, College of Medicine, Ningbo University, Ningbo, Zhejiang, PR China
| | - Congyang Huang
- Department of Nephrology, Ningbo Urology and Nephrology Hospital, College of Medicine, Ningbo University, Ningbo, Zhejiang, PR China
| | - Yongyao Wu
- Department of Nephrology, Beilun Branch of the First Affiliated Hospital, College of Medicine, Zhejiang University, Ningbo, Zhejiang, PR China
| | - Min Ni
- Department of Psychiatry, Beilun Branch of the First Affiliated Hospital, College of Medicine, Zhejiang University, Ningbo, Zhejiang, PR China
| | - Jinfeng Duan
- Department of Psychiatry, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China
| | - Jianghua Chen
- Department of Nephrology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China
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Han SW, Kim SJ, Lee DJ, Kim KM, Joo NS. The Relationship between Serum 25-Hydroxyvitamin D, Parathyroid Hormone and the Glomerular Filtration Rate in Korean Adults: The Korea National Health and Nutrition Examination Survey between 2009 and 2011. Korean J Fam Med 2014; 35:98-106. [PMID: 24724005 PMCID: PMC3978191 DOI: 10.4082/kjfm.2014.35.2.98] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2013] [Accepted: 02/27/2014] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND The glomerular filtration rate (GFR) decreases with age, while parathyroid hormone (PTH) increases. There are a few reports only on the relationship between GFR and PTH under the category of serum 25-hydroxyvitamin D (25[OH]D) concentration. METHODS Using the Korea National Health and Nutrition Examination Survey (KNHANES) data, a cross-sectional study was conducted on the association between serum 25(OH)D concentration, GFR and PTH in Korean adults aged 50 years or older. Serum PTH concentration was compared to the tertiles of GFR after adjustment for relevant variables. In addition, the serum PTH concentration was compared with the GFR under the category of serum 25(OH) D concentration (<20, 20-30, >30 ng/mL). RESULTS The mean estimated GFR (eGFR) was 74.8 mL/min in men and 73.1 mL/min in women. The mean PTH and 25(OH) D was 66.8 pg/mL, 20.5 ng/mL in men and 69.0 pg/mL, 18.2 ng/mL in women. The serum PTH concentration showed a significant negative correlation with the serum 25(OH) D and eGFR in both genders. The serum PTH concentration significantly increased at the lower tertile of eGFR in male adults In addition, a decrease of serum PTH concentration was marked in the vitamin D sufficient male adults (>30 ng/mL). CONCLUSION This present study demonstrated that serum PTH concentration showed negative correlation with eGFR, however, serum PTH increase may be minimized by maintaining proper serum 25(OH)D concentrations under similar eGFR status in Korean adults aged 50 and above.
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Affiliation(s)
- Sung-Woo Han
- Department of Family Practice and Community Health, Ajou University School of Medicine, Suwon, Korea
| | - Sung-Jin Kim
- Department of Family Practice and Community Health, Ajou University School of Medicine, Suwon, Korea
| | - Duck-Joo Lee
- Department of Family Practice and Community Health, Ajou University School of Medicine, Suwon, Korea
| | - Kwang-Min Kim
- Department of Family Practice and Community Health, Ajou University School of Medicine, Suwon, Korea
| | - Nam-Seok Joo
- Department of Family Practice and Community Health, Ajou University School of Medicine, Suwon, Korea
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Immune, metabolic and epidemiological aspects of vitamin D in chronic kidney disease and transplant patients. Clin Biochem 2014; 47:509-15. [PMID: 24412344 DOI: 10.1016/j.clinbiochem.2013.12.026] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2013] [Revised: 12/27/2013] [Accepted: 12/28/2013] [Indexed: 12/19/2022]
Abstract
Chronic kidney disease strongly impacts on mineral and bone metabolism. Despite numerous medications, the biological targets recommended by international guidelines are often unmet. Among the treatment armamentarium, native or nutritional vitamin D (25OHD3) has been rediscovered in the early 2000s, and its general and specific actions further studied. Effects on bone, immunity, infection prevention, muscle function and phosphocalcic metabolism have been reviewed. Assessment of nutritional vitamin D status showed very low serum 25OHD3 levels and increase in nutritional vitamin D prescription led to improvement in these levels. However, about 45% of adult CKD patients still have insufficient serum 25OHD3 levels. Epidemiological studies should be enforced to describe further the mineral and bone disease management in CKD.
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