Extrarenal Production of Calcitriol in Normal and Uremic Humans*

Dusso, Adriana; Finch, Jane; Brown, Alex; Ritter, Cynthia S.; Delmez, James A.; Schreiner, George F.; Slatopolsky, Eduardo

doi:10.1210/jcem-72-1-157

Cited by 120 publications

(92 citation statements)

References 54 publications

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“…We have found circulating levels of activated vitamin D [1,25(OH) 2 D] to contribute to VDR protein levels, confirming earlier in vitro studies in PBMCs (45,49), whereas total VDR mRNA (the amplicon used in this study amplifies all mRNA species) was a borderline determinant of VDR protein levels in the PBMCs. In contrast, the insulin secretory capacity was a predictor of PBMC mRNA but not protein.…”

Section: Discussionsupporting

confidence: 88%

“…It is therefore of interest that we observed significant variation of VDR mRNA with the FokI polymorphism. Because PBMC production of activated vitamin D increases in vitamin D deficiency (45), FokI genotype may contribute to feedback control of expression of the 25-hydroxyvitamin D-1-␣-hydroxylase (CYP27B1) gene, located in the same chromosomal region as the VDR gene and active in PBMCs (46,47). Alternatively, the FokI polymorphism may interfere with formation of VDR heterodimers with the retinoid X receptor to form effector complexes (48).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Vitamin D Receptor (VDR) mRNA and VDR Protein Levels in Relation to Vitamin D Status, Insulin Secretory Capacity, and VDR Genotype in Bangladeshi Asians

et al. 2002

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Associations have been reported between vitamin D receptor (VDR) gene polymorphisms, type 1 diabetes, insulin secretion, and the insulin resistance syndrome. As VDR polymorphisms have no known functional significance, these findings may implicate a variant of the VDR gene or a locus in linkage disequilibrium with the VDR. We have examined VDR mRNA and VDR protein levels in relation to VDR polymorphisms (41 Bangladeshi subjects) and analyzed insulin secretory capacity (143 Bangladeshi subjects), allowing for other known determinants. Peripheral blood mononuclear cells (PBMCs) from subjects who had been genotyped for BsmI, ApaI, TaqI, and FokI VDR restriction fragment length polymorphisms were used for both total VDR mRNA quantitation (using TaqMan) and measurement of VDR protein levels (using a specific microimmunoassay). Stepwise multiple regression analyses were used (to P < 0.05) to analyze the data. For the insulin secretion index, the best-fit model (n ‫؍‬ 143, P < 0.0001) gave age (P ‫؍‬ 0.002), TaqI (P < 0.0001), and BMI (P ‫؍‬ 0.001) as independent determinants; with the inclusion of VDR mRNA and VDR protein levels, VDR mRNA was the sole independent determinant (n ‫؍‬ 41, P ‫؍‬ 0.024). However, the best-fit model for VDR mRNA (P ‫؍‬ 0.004) gave FokI (P ‫؍‬ 0.044) and TaqI (P ‫؍‬ 0.04) genotypes and insulin secretory capacity (P ‫؍‬ 0.042) as independent determinants. For VDR protein levels, the best-fit model (P ‫؍‬ 0.006) gave TaqI genotype (P ‫؍‬ 0.005) and circulating 1,25-dihydroxyvitamin-D levels (P ‫؍‬ 0.03) as independent determinants. In conclusion, these studies confirm an association between VDR polymorphisms and insulin secretory capacity and demonstrate the VDR genotype to be a significant determinant of VDR mRNA and VDR protein levels in PBMCs, providing functional support to previously described genetic associations with the VDR gene. Furthermore, VDR expression has been shown to be a determinant of insulin secretory capacity. Because the VDR is expressed in a large number of tissues, it is not surprising that ligand-activated VDR modulates the expression of many genes. The VDR gene, located on chromosome 12q, has 14 exons, 6 of which are in the 5Ј untranslated region (1a-1f). At least 22 unique nonfunctional VDR variants have been described, most of which lead to rare syndromes associated with vitamin D-resistant rickets (4). A number of common chronic disorders of inflammatory, infective, and autoimmune etiologies, including both type 1 and type 2 diabetes and colorectal adenoma, have been shown to be associated with specific polymorphisms of the vitamin D receptor gene, although not all such associ-

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Vitamin D Receptor (VDR) mRNA and VDR Protein Levels in Relation to Vitamin D Status, Insulin Secretory Capacity, and VDR Genotype in Bangladeshi Asians

et al. 2002

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“…Some studies found circulating levels of activated vitamin D (1,25(OH)2D) contribute to VDR protein levels [4,[12][13][14]. In a study in patients with pulmonary tuberculosis was reported that an increase in the level of 1,25-(OH)2D3, but the VDR protein levels decreased.…”

Section: Introductionmentioning

confidence: 99%

The Correlation between Serum Concentration of Vitamin D with Vitamin D Receptor Expression and Disease Activity in Indonesian Patients with Systemic Lupus Erythematosus: Preliminary Study

Handono¹,

Tanuwijaya²,

Fitri³

et al. 2014

JTLS

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The vitamin D role on the immune response of systemic lupus erythematosus (SLE) patient is mediated by vitamin D receptor (VDR). Low level of vitamin D correlated with disease activity in SLE patients, and circulating levels of activated vitamin D (1,25(OH)2D) contribute to VDR protein levels and its function. The objective of this study was to determine the correlation between vitamin D status with expression of VDR in peripheral blood mononuclear cell (PBMC) and the disease activity in SLE patients. The Research Subjects were 15 SLE patients (ACR 1997 criteria) fr om the RheumatoImmunology Division, dr. Saiful Anwar Hospital, Malang and 5 healthy controls. Serum vitamin D (25(OH)D3) level was assessed using ELISA method. VDR expression in PBMC was assessed using immunocytochemistry technique. The disease activity was measured by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score. This study showed no difference on VDR expression in PBMC between patient and healthy control group, but patient with vitamin D deficiency had lower VDR expression in PBMC than the other group. No difference on SLEDAI score between the group. Vitamin D status correlated positively with VDR expression in PBMC (p < 0,035, r = 0,473). However vitamin D status did not correlate with disease activity scores (p = 0,686).

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“…It was previously thought that CKD and dialysis patients should only be given alfacalcidol (1-alpha hydroxyvitamin D3) or doxercalciferol (1-alpha hydroxyvitamin D2) which will then undergo 25-hydroxylation in the liver to form the active 1,25-dihydroxyvitamin D. However, other sites in the body, such as skin, lymph nodes and macrophages, also have 1 -hydroxylation activity (88,89). To confirm this, several studies have shown that native vitamin D3 (cholecalciferol) supplementation improves 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 levels in dialysis patients (85)(86)(87).…”

Section: Native Vitamin Dmentioning

confidence: 99%

Pharmacological Management of Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease

Salam

Khwaja

Wilkie

2016

Drugs

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or Article Brief (if supplied by editors): As a 'Therapy in Practice' article, we would like this to provide a succinct, up-to-date clinically orientated guide to the optimum management of secondary hyperparathyroidism in patients with chronic kidney disease. The review should include an appropriate background to the development of SHPT. It should focus primarily on pharmacological treatments but as appropriate, non-pharmacological approaches (dietary, surgical) may be discussed to fully place pharmacological therapy in context. Submission date: 31 st March 2016Word count: 4156 Compliance with Ethical StandardsFunding and conflict of interest statement from each author: Takeaway messages from the article SHPT is associated with adverse outcomes in CKD and dialysis patients  Optimum PTH level is unclear in pre-dialysis CKD and the recommended range is wide for dialysis patients.  Management of SHPT is largely pharmacological focussing on lowering PTH  PTH lowering treatment has not shown improved cardiovascular risk, fractures and mortality. AbstractSecondary hyperparathyroidism (SHPT) is a common complication of CKD and is part of the chronic kidney disease-mineral bone disorder (CKD-MBD). SHPT is associated with increased risk of fracture and mortality, thus SHPT control is recommended as kidney function declines. Effective SHPT management becomes more difficult once skeletal and cardiovascular adverse effects associated with severe SHPT have become established. However, interventional studies to lower parathyroid hormone (PTH) have so far shown inconsistent results in improving patient-centred outcomes such as mortality, cardiovascular events and fracture. Pharmacological treatment effect on PTH level is also inconsistent between predialysis CKD and dialysis patients which adds to the complexity of SHPT management. This review aims to give an overview on the pathophysiology, pharmacological and non-pharmacological treatment for SHPT in CKD including some of the limitations of current therapeutic options.

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Extrarenal Production of Calcitriol in Normal and Uremic Humans*

Cited by 120 publications

References 54 publications

Vitamin D Receptor (VDR) mRNA and VDR Protein Levels in Relation to Vitamin D Status, Insulin Secretory Capacity, and VDR Genotype in Bangladeshi Asians

Vitamin D Receptor (VDR) mRNA and VDR Protein Levels in Relation to Vitamin D Status, Insulin Secretory Capacity, and VDR Genotype in Bangladeshi Asians

The Correlation between Serum Concentration of Vitamin D with Vitamin D Receptor Expression and Disease Activity in Indonesian Patients with Systemic Lupus Erythematosus: Preliminary Study

Pharmacological Management of Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease

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