Vitamin D in Health and Disease (2nd Edition)

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 19187

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Guest Editor
Head of Allergology and Clinical Immunology Unit, Department of Internal Medicine, University of Genoa and San Bartolomeo Hospital, Sarzana, Italy
Interests: immunodeficiency; autoimmunity; neuro-endocrino-immunology; pharmacogenomics; soluble molecules; immune-mediated diseases; allergies; vaccines
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Guest Editor
Department of Clinical and Experimental Medicine, School and Operative Unit of Allergy and Clinical Immunology, University of Messina, 98125 Messina, Italy
Interests: inflammatory mediators; the citokine network (interleukins, chemokines, adhesion molecules, lipoxines); the oxidative stress in various areas of clinical immunology; allergy; oncology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Vitamin D (VD) is a lipo-soluble hormone well known for its effects on calcium homeostasis and bone metabolism. Recently there has been growing interest in the extra-skeletal effects of VD. In particular, recent studies have highlighted how VD plays a fundamental role in immunomodulation processes in the context of both innate and adaptive immunity, with consequent anti-inflammatory and anti-oxidant effect in different immune-mediated pathologies, such as systemic sclerosis, psoriasis, atopic dermatitis and rheumatoid arthritis; as well as in various pro-inflammatory processes affecting the airways. Recent evidence has shown that VD is also closely related to other components such as the microbiome, with which it appears to be interconnected in the pathophysiology of many allergic diseases. In addition to the known immunomodulatory effects of VD, several studies have reported that it is also endowed with important anti-proliferative, anti-angiogenic and pro-differentiative effects in cancer thanks to its effects on the modulation of the expression of tumor miRNAs through its action at the VD receptor (VDR) level. In view of this, it is clear that VD supplementation represents a safe and valid therapeutic strategy capable of improving the clinical outcome of many diseases.

Dr. Giuseppe Murdaca
Prof. Dr. Sebastiano Gangemi
Guest Editors

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Keywords

  • vitamin D and the immune system
  • vitamin D and cytokines
  • vitamin D and microbiome
  • vitamin D and respiratory diseases
  • vitamin D and autoimmune diseases
  • vitamin D and allergies

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Published Papers (10 papers)

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Editorial

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2 pages, 135 KiB  
Editorial
Vitamin D in Health and Disease 2.0
by Giuseppe Murdaca and Sebastiano Gangemi
Biomedicines 2024, 12(2), 324; https://doi.org/10.3390/biomedicines12020324 - 31 Jan 2024
Viewed by 590
Abstract
Vitamin D (VD) is a fat-soluble vitamin considered essential for human health, and its levels are associated with the function and composition of the intestinal microbiome [...] Full article
(This article belongs to the Special Issue Vitamin D in Health and Disease (2nd Edition))

Research

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12 pages, 693 KiB  
Article
Oxidative Stress Markers and Heat Shock Proteins in Non-Obese Women with Polycystic Ovary Syndrome Are Not Elevated and Show No Correlation with Vitamin D
by Manjula Nandakumar, Thozhukat Sathyapalan, Alexandra E. Butler and Stephen L. Atkin
Biomedicines 2023, 11(7), 2044; https://doi.org/10.3390/biomedicines11072044 - 20 Jul 2023
Viewed by 1128
Abstract
Introduction. Oxidative stress (OS) is recognized in the pathophysiology of polycystic ovary syndrome (PCOS). OS results in intracellular reactive oxygen species generation, causing oxidative protein damage that is protected by heat shock proteins (HSPs). Vitamin D is thought to reduce and protect against [...] Read more.
Introduction. Oxidative stress (OS) is recognized in the pathophysiology of polycystic ovary syndrome (PCOS). OS results in intracellular reactive oxygen species generation, causing oxidative protein damage that is protected by heat shock proteins (HSPs). Vitamin D is thought to reduce and protect against OS; therefore, OS, HSP, and vitamin D levels may be associated with PCOS. However, their expression in PCOS without underlying inflammation is unknown. Methods. In this exploratory study, the plasma levels of 7 OS proteins and 10 HSPs that are affected by the OS process were measured using Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurements in non-obese, non-insulin resistant women with PCOS (n = 24) without systemic inflammation and control (n = 24) women; the cohorts were matched for weight and age. The OS proteins and HSPs were correlated with 25-hydroxy vitamin D3 (25(OH)D3) and the active form, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), as measured by isotope-dilution liquid chromatography tandem mass spectrometry. Results. The PCOS women versus the controls had comparable insulin resistance and systemic inflammation (C-reactive protein 2.0 mg/L vs. 2.3 mg/L, p > 0.05), but higher free androgen index and anti-mullerian hormone levels. Among the OS proteins, only esterase D (ESD; p < 0.01) was elevated in PCOS and the HSPs did not differ between the PCOS and control women. There was no correlation of 25(OH)D3 or 1,25(OH)2D3 with any of the proteins. Conclusions. In a PCOS population that was non-obese and without insulin resistance and systemic inflammation, only ESD was elevated in PCOS, whilst the other OS proteins and HSPs were not elevated. Further, none of the OS proteins or HSPs were correlated with either 25(OH)D3 or 1,25(OH)2D3 in either cohort of women or when both cohorts were combined, indicating that the OS and HSP responses were largely absent and not affected by vitamin D in a non-obese PCOS population. Full article
(This article belongs to the Special Issue Vitamin D in Health and Disease (2nd Edition))
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13 pages, 1113 KiB  
Article
Association of Blood Levels of Vitamin D and Its Binding Protein with Clinical Phenotypes of Multiple Sclerosis
by Suhail Al-Shammri, Arpita Chattopadhyay, Magdy Girgis Hanah, Suhail Doi and Abayomi Akanji
Biomedicines 2023, 11(7), 1808; https://doi.org/10.3390/biomedicines11071808 - 24 Jun 2023
Cited by 1 | Viewed by 965
Abstract
Background: Low vitamin D levels may synergize with changing levels of the vitamin D binding protein (DBP) to precipitate in the development and clinical progression of multiple sclerosis (MS). In this study, this hypothesis was explored in groups of Kuwaiti healthy controls and [...] Read more.
Background: Low vitamin D levels may synergize with changing levels of the vitamin D binding protein (DBP) to precipitate in the development and clinical progression of multiple sclerosis (MS). In this study, this hypothesis was explored in groups of Kuwaiti healthy controls and patients with different clinical phenotypes of MS. Methods: Fasting serum concentrations of 25-hydroxyvitamin D [25(OH)D] and DBP were measured in 146 healthy controls and 195 patients with MS. The latter were classified according to the duration, type, and onset of the disease and the mode of treatment. Factors such as relapse/remitting, and the use of nutritional supplements were also considered. Results: The DBP levels were significantly lower in the patients than in the controls. This was more evident in newly diagnosed drug-naïve patients than in those patients with more established MS. MS status and severity were negatively impacted by concurrently low levels of 25(OH)D and DBP. This was most clearly expressed in drug-naïve patients and in those with a disease in relapse. It was also established that the 25(OH)D level had a significant positive correlation with the duration of the disease. Conclusion: Lower levels of 25(OH)D and DBP appear to have a synergistic effect on MS status. This was most clearly demonstrated in patients who were newly diagnosed (drug-naïve) and in those patients who were in relapse. Full article
(This article belongs to the Special Issue Vitamin D in Health and Disease (2nd Edition))
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12 pages, 1808 KiB  
Article
Association between Organochlorine Pesticides and Vitamin D in Female Subjects
by Edwina Brennan, Alexandra E. Butler, Manjula Nandakumar, Daniel S. Drage, Thozhukat Sathyapalan and Stephen L. Atkin
Biomedicines 2023, 11(5), 1451; https://doi.org/10.3390/biomedicines11051451 - 15 May 2023
Cited by 1 | Viewed by 1637
Abstract
In human population studies, organochlorine pesticides (OCPs) have been linked to vitamin D deficiency. Therefore, this study examined the association between OCPs, vitamin D3 (cholecalciferol, 25(OH)D3), and the active metabolite 1,25-dihydrovitamin D3 (1,25(OH)2D3) in a [...] Read more.
In human population studies, organochlorine pesticides (OCPs) have been linked to vitamin D deficiency. Therefore, this study examined the association between OCPs, vitamin D3 (cholecalciferol, 25(OH)D3), and the active metabolite 1,25-dihydrovitamin D3 (1,25(OH)2D3) in a cohort of non-obese women. The serum samples of 58 female participants (age—31.9 ± 4.6 years; body mass index (BMI)—25.7 ± 3.7 kg/m2) were screened for 10 indicator OCPs. 25(OH)D3 and 1,25(OH)2D3 levels were determined via isotope dilution liquid chromatography tandem mass spectrometry. In this cohort, the 25(OH)D3 and 1,25(OH)2D3 levels were 22.9 ± 11.2 ng/mL and 0.05 ± 0.02 ng/mL, respectively, with 28 participants classified as 25(OH)D3-deficient (<50 nmol/L). In the study cohort, no correlations were found between individual or total OCPs (ƩOCPs) and 25(OH)D3. p,p′-dichlorodiphenyldichloroethylene (DDE) and ƩOCPs correlated positively with 1,25(OH)2D3, with the latter being negatively correlated with estimated glomerular filtration rate (eGFR). In women with sufficient 25(OH)D3 levels, p,p′-dichlorodiphenyltrichloroethan (DDT) was positively correlated with 1,25(OH)2D3, whilst in the deficient group, hexachlorobenzene (HCB) and p,p′-(DDE) were positively correlated with 1,25(OH)2D3, β-Hexachlorocyclohexane (HCH) was positively correlated with 25(OH)D3, and none of the OCPs were associated with measures of renal function. Overall, OCPs and ƩOCPs were not associated with 25(OH)D3, suggesting that they are unrelated to vitamin D deficiency, but p,p′-DDE and ƩOCPs correlated positively with active 1,25(OH)2D3, while ƩOCPs correlated negatively with eGFR, suggesting a possible renal effect. Analysis of vitamin D deficiency revealed an association between β-HCH and 25(OH)D3, and between HCB and p,p′-DDE and 1,25(OH)2D3, suggesting that OCP effects may be enhanced in cases of vitamin D deficiency. Full article
(This article belongs to the Special Issue Vitamin D in Health and Disease (2nd Edition))
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16 pages, 1009 KiB  
Article
Effect of Single High Dose Vitamin D Substitution in Hospitalized COVID-19 Patients with Vitamin D Deficiency on Length of Hospital Stay
by Fabienne Jaun, Maria Boesing, Giorgia Luethi-Corridori, Kristin Abig, Nando Bloch, Stéphanie Giezendanner, Victoria Grillmayr, Philippe Haas, Anne B. Leuppi-Taegtmeyer, Jürgen Muser, Andrea Raess, Philipp Schuetz, Michael Brändle and Jörg D. Leuppi
Biomedicines 2023, 11(5), 1277; https://doi.org/10.3390/biomedicines11051277 - 25 Apr 2023
Cited by 1 | Viewed by 1354
Abstract
Vitamin D and its role in the coronavirus-19 disease (COVID-19) pandemic has been controversially discussed, with inconclusive evidence about vitamin D3 (cholecalciferol) supplementation in COVID-19 patients. Vitamin D metabolites play an important role in the initiation of the immune response and can be [...] Read more.
Vitamin D and its role in the coronavirus-19 disease (COVID-19) pandemic has been controversially discussed, with inconclusive evidence about vitamin D3 (cholecalciferol) supplementation in COVID-19 patients. Vitamin D metabolites play an important role in the initiation of the immune response and can be an easily modifiable risk factor in 25-hydroxyvitamin D3 (25(OH)D3)-deficient patients. This is a multicenter, randomized, placebo-controlled double-blind trial to compare the effect of a single high dose of vitamin D3 followed by treatment as usual (TAU) of daily vitamin D3 daily until discharge versus placebo plus TAU in hospitalized patients with COVID-19 and 25(OH)D3-deficiency on length hospital stay. We included 40 patients per group and did not observe a significant difference in the median length of hospital stay (6 days in both groups, p = 0.920). We adjusted the length of stay for COVID-19 risk factors (β = 0.44; 95% CI: −2.17–2.22), and center (β = 0.74; 95% CI: −1.25–2.73). The subgroup analysis in patients with severe 25(OH)D3-deficiency (<25 nmol/L) showed a non-significant reduction in the median length of hospital stay in the intervention group (5.5 vs. 9 days, p = 0.299). The competing risk model with death did not reveal significant differences between the group in the length of stay (HR = 0.96, 95% CI 0.62–1.48, p = 0.850). Serum 25(OH)D3 level increased significantly in the intervention group (mean change in nmol/L; intervention: +26.35 vs. control: –2.73, p < 0.001). The intervention with 140,000 IU vitamin D3 + TAU did not significantly shorten the length of hospital stay but was effective and safe for the elevation of serum 25(OH)D3 levels. Full article
(This article belongs to the Special Issue Vitamin D in Health and Disease (2nd Edition))
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12 pages, 1595 KiB  
Article
Frequency of Vitamin D Receptor Gene Polymorphisms in a Population with a very High Prevalence of Vitamin D Deficiency, Obesity, Diabetes and Hypertension
by Salah Gariballa, Ghada S. M. Al-Bluwi and Javed Yasin
Biomedicines 2023, 11(4), 1202; https://doi.org/10.3390/biomedicines11041202 - 18 Apr 2023
Cited by 2 | Viewed by 1768
Abstract
Background: Although vitamin D levels and underlying vitamin D receptor (VDR) genetic polymorphisms have been linked to many common diseases including obesity, the association remains unclear. There is also co-existence of pathologically high proportions of obesity and vitamin D deficiency conditions in our [...] Read more.
Background: Although vitamin D levels and underlying vitamin D receptor (VDR) genetic polymorphisms have been linked to many common diseases including obesity, the association remains unclear. There is also co-existence of pathologically high proportions of obesity and vitamin D deficiency conditions in our UAE society. We therefore aimed to determine the genotypes and allele percentage frequency distribution of four polymorphisms—FokI, BsmI, ApaI and TaqI—in the VDR gene in healthy Emirati individuals and their association with vitamin D levels and chronic conditions including diabetes mellitus, hypertension and obesity. Methods: 277 participants who were part of a randomized controlled trial had their assessment that included clinical and anthropometric data. Whole blood samples were taken for measurements of vitamin D [25(OH) D], four vitamin D receptor gene polymorphism SNPs, including BsmI, FokI, TaqI and ApaI, metabolic and inflammatory markers and related biochemical variables. Multiple logistic regression analysis was used to assess the influence of vitamin D receptor gene SNPs on vitamin D status after adjusting for clinical parameters known to influence vitamin D status in the study population. Results: Overall, 277 participants with a mean (±SD) age of 41 ± 12, 204 (74%) of them being female, were included in the study. There were statistically significant differences in vitamin D concentrations between different genotypes of the four VDR gene polymorphisms (p < 0.05). There were, however, no statistically significant differences in vitamin D concentrations between subjects with and those without the four VDR gene polymorphisms genotype and alleles except for AA and AG and allele G in Apal SNP (p < 0.05). Multivariate analysis revealed no significant independent associations between vitamin D status and the four VDR gene polymorphisms after adjusting for dietary intake, physical activity, sun exposure, smoking and body mass index. In addition, no significant differences were found in the frequency of the genotypes and alleles of the four VDR genes among patients with obesity, diabetes and hypertension compared to those without these medical conditions. Conclusions: Although we found statistically significant differences in vitamin concentrations between different genotypes of the four VDR gene polymorphisms, multivariate analysis revealed no association after adjusting for clinical parameters known to influence vitamin D status. Furthermore, no association was found between obesity and related pathologies and the four VDR gene polymorphisms. Full article
(This article belongs to the Special Issue Vitamin D in Health and Disease (2nd Edition))
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Review

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16 pages, 1467 KiB  
Review
Mast Cells and Vitamin D Status: A Clinical and Biological Link in the Onset of Allergy and Bone Diseases
by Giuseppe Murdaca, Alessandro Allegra, Alessandro Tonacci, Caterina Musolino, Luisa Ricciardi and Sebastiano Gangemi
Biomedicines 2022, 10(8), 1877; https://doi.org/10.3390/biomedicines10081877 - 03 Aug 2022
Cited by 8 | Viewed by 3090
Abstract
The immune system is made up by an extremely composite group of cells, whose regulated and harmonious activity is fundamental to maintain health. The mast cells are an essential effector of inflammatory response which is characterized by a massive release of mediators accumulated [...] Read more.
The immune system is made up by an extremely composite group of cells, whose regulated and harmonious activity is fundamental to maintain health. The mast cells are an essential effector of inflammatory response which is characterized by a massive release of mediators accumulated in cytoplasmic secretory granules. However, beyond the effects on immune response, mast cells can modify bone metabolism and are capable of intervening in the genesis of pathologies such as osteoporosis and osteopenia. Vitamin D is recognized to induce changes in bone metabolism, but it is also able to influence immune response, suppressing mast cell activation and IgE synthesis from B cells and increasing the number of dendritic cells and IL-10-generating regulatory T cells. Vitamin D deficit has been reported to worsen sensitization and allergic manifestations in several different experimental models. However, in clinical situations, contradictory findings have been described concerning the correlation between allergy and vitamin D deficit. The aim of this review was to analyze the close relationships between mast cells and vitamin D, which contribute, through the activation of different molecular or cellular activation pathways, to the determination of bone pathologies and the onset of allergic diseases. Full article
(This article belongs to the Special Issue Vitamin D in Health and Disease (2nd Edition))
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Other

18 pages, 2167 KiB  
Systematic Review
Immunomodulatory Role of Vitamin D on Gut Microbiome in Children
by Anika Tabassum, Adli Ali, Farah Dayana Zahedi and Noor Akmal Shareela Ismail
Biomedicines 2023, 11(5), 1441; https://doi.org/10.3390/biomedicines11051441 - 14 May 2023
Cited by 1 | Viewed by 3039
Abstract
Vitamin D plays a role in regulating the immune system and can be linked to the alteration of the gut microbiome, which leads to several immunological diseases. This systematic review aims to explore the relationship between Vitamin D and children’s gut microbiome, as [...] Read more.
Vitamin D plays a role in regulating the immune system and can be linked to the alteration of the gut microbiome, which leads to several immunological diseases. This systematic review aims to explore the relationship between Vitamin D and children’s gut microbiome, as well as its impact towards the immune system. We have systematically collated relevant studies from different databases concerning changes in the gut microbiome of children from infants to 18 years old associated with Vitamin D and the immunological pathways. The studies utilized 16S rRNA sequencing analysis of fecal matter with or without Vitamin D supplementation and Vitamin D levels. Ten studies were selected for the review, among which eight studies showed significant alterations in the gut microbiome related to Vitamin D supplementation or Vitamin D levels. The taxa of the phylum Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria are the most altered in these studies. The alteration of the taxa alters the Th1 and Th2 pathways and changes the immune response. We will discuss how Vitamin D may contribute to the activation of immune pathways via its effects on intestinal barrier function, microbiome composition, and/or direct effects on immune responses. In conclusion, the studies examined in this review have provided evidence that Vitamin D levels may have an impact on the composition of children’s gut microbiomes. Full article
(This article belongs to the Special Issue Vitamin D in Health and Disease (2nd Edition))
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17 pages, 2153 KiB  
Systematic Review
Chronic Hepatitis B and Related Liver Diseases Are Associated with Reduced 25-Hydroxy-Vitamin D Levels: A Systematic Review and Meta-Analysis
by Anindita Banerjee, Shreyasi Athalye, Naveen Khargekar, Poonam Shingade and Manisha Madkaikar
Biomedicines 2023, 11(1), 135; https://doi.org/10.3390/biomedicines11010135 - 05 Jan 2023
Cited by 1 | Viewed by 2549
Abstract
Hepatitis B infection is a major public health problem globally leading to chronic liver disease and death, which are influenced by various environmental and host factors including serum 25-hydroxy-vitamin D levels. There is no comprehensive systematic review reporting the association of serum 25-hydroxy-vitamin [...] Read more.
Hepatitis B infection is a major public health problem globally leading to chronic liver disease and death, which are influenced by various environmental and host factors including serum 25-hydroxy-vitamin D levels. There is no comprehensive systematic review reporting the association of serum 25-hydroxy-vitamin D levels and different stages of chronic hepatitis B. This study aimed to analyze the association of 25-hydroxy-vitamin D levels in chronic hepatitis B with various determinants and outcomes. A bibliographic search in PubMed, Google Scholar, and Scopus was conducted using the search terms “Vitamin D”, “cholecalciferol”, “calcitriol”, “Hepatitis B”, and “HBV”, which were published until September 2022. Meta-analysis using the “metafor” package in R was conducted with a random effect model. This analysis included 33 studies with 6360 chronic hepatitis B patients. The pooled estimates of serum 25-hydroxy-vitamin D level among CHB cases was 21.05 ng/mL and was significantly lower compared to healthy controls. (p < 0.005). Reduced serum 25-hydroxy-vitamin D level was significantly associated with the severity of liver fibrosis as well as HBe positivity. This analysis suggests that serum 25-hydroxy-vitamin D levels are associated with disease activity and pathobiology, although the exact nature of the cause–effect relationship cannot be discerned from this study. Full article
(This article belongs to the Special Issue Vitamin D in Health and Disease (2nd Edition))
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14 pages, 633 KiB  
Systematic Review
Systematic Review of the Treatment of Persistent Hyperparathyroidism Following Kidney Transplantation
by Miłosz Miedziaszczyk, Katarzyna Lacka, Oskar Tomczak, Aleksander Bajon, Marta Primke and Ilona Idasiak-Piechocka
Biomedicines 2023, 11(1), 25; https://doi.org/10.3390/biomedicines11010025 - 22 Dec 2022
Cited by 7 | Viewed by 2367
Abstract
Chronic kidney disease–mineral and bone disorder is one of the complications associated with chronic kidney disease. About 10–50% of patients following kidney transplantation have persistent hyperparathyroidism. Hypercalcaemic hyperparathyroidism has a negative impact on the kidney transplant outcome; therefore, it requires treatment. The data [...] Read more.
Chronic kidney disease–mineral and bone disorder is one of the complications associated with chronic kidney disease. About 10–50% of patients following kidney transplantation have persistent hyperparathyroidism. Hypercalcaemic hyperparathyroidism has a negative impact on the kidney transplant outcome; therefore, it requires treatment. The data regarding the treatment of persistent hyperparathyroidism provided in scientific publications are divergent and contradictory. Therefore, the aim of our systematic review was to evaluate the efficacy of persistent hyperparathyroidism treatment in patients following kidney transplantation. The Cochrane, PubMed, and Scopus databases were browsed independently by two authors. The search strategy included controlled vocabulary and keywords. The effectiveness of calcitriol, paricalcitol, cinacalcet, and parathyroidectomy was compared and analysed. The mean calcium and parathormone (PTH) concentrations per patient in the group of paricalcitol increased by 1.27% and decreased by 35.14% (n = 248); in the group of cinacalcet decreased by 12.09% and 32.16% (n = 368); and in the group of parathyroidectomy decreased by 19.06% and 86.49% (n = 15) at the end of the study compared to the baseline (n = 244, n = 342 and n = 15), respectively. Paricalcitol, cinacalcet, and parathyroidectomy decreased the intact PTH level. Cinacalcet and parathyroidectomy lowered calcium levels in renal transplant patients with hypercalcaemia. Conversely, paricalcitol increased the serum calcium concentration. Cinacalcet seems to be a good candidate in the treatment of post-transplant hyperparathyroidism. Full article
(This article belongs to the Special Issue Vitamin D in Health and Disease (2nd Edition))
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