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Article ; Online: Vitamin K and vascular calcification.

Lees, Jennifer S / Mark, Patrick B / Witham, Miles D

Current opinion in nephrology and hypertension

2021 Volume 30, Issue 4, Page(s) 430–436

Abstract: ... of vascular calcification implicate vitamin K-dependent proteins as important regulators in this process. This review ... evolving field.: Recent findings: Vitamin K deficiency is associated with increasing severity ... inconsistent. Vitamin K may reduce calcification propensity by improving the activity of vitamin K-dependent ...

Abstract	Purpose of review: Vascular calcification is a common and important cardiovascular risk factor in patients with chronic kidney disease (CKD). Recent advances in the understanding of the biology of vascular calcification implicate vitamin K-dependent proteins as important regulators in this process. This review highlights recent key advances in vascular biology, epidemiology, and clinical trials in this rapidly evolving field. Recent findings: Vitamin K deficiency is associated with increasing severity of vascular calcification among patients with CKD, but the relationship with cardiovascular disease and mortality is inconsistent. Vitamin K may reduce calcification propensity by improving the activity of vitamin K-dependent calcification inhibitors or by down-regulating components of the innate immune system to reduce inflammation. However, recent randomized controlled trials in patients with diabetes, CKD, renal transplant, and on hemodialysis have failed to demonstrate improvement in vascular calcification or stiffness after vitamin K treatment. Summary: Current evidence does not support a clinically useful role for vitamin K supplementation to prevent or reverse vascular calcification in patients with CKD. Knowledge gaps remain, particularly whether higher doses of vitamin K, longer duration of supplementations, or use a vitamin K as a part of a package of measures to counteract vascular calcification might be effective.
MeSH term(s)	Humans ; Renal Dialysis ; Renal Insufficiency, Chronic/therapy ; Vascular Calcification/drug therapy ; Vascular Calcification/epidemiology ; Vitamin K ; Vitamin K Deficiency/drug therapy ; Vitamin K Deficiency/epidemiology
Chemical Substances	Vitamin K (12001-79-5)
Language	English
Publishing date	2021-03-31
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1151092-4
ISSN	1473-6543 ; 1535-3842 ; 1062-4813 ; 1062-4821
ISSN (online)	1473-6543 ; 1535-3842
ISSN	1062-4813 ; 1062-4821
DOI	10.1097/MNH.0000000000000712
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Article ; Online: The ViKTORIES trial: A randomized, double-blind, placebo-controlled trial of vitamin K supplementation to improve vascular health in kidney transplant recipients.

Lees, Jennifer S / Rankin, Alastair J / Gillis, Keith A / Zhu, Luke Y / Mangion, Kenneth / Rutherford, Elaine / Roditi, Giles H / Witham, Miles D / Chantler, Donna / Panarelli, Maurizio / Jardine, Alan G / Mark, Patrick B

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

2021 Volume 21, Issue 10, Page(s) 3356–3368

Abstract: ... vitamin K deficiency. We performed a single-center, phase II, parallel-group, randomized, double-blind ... placebo-controlled trial (ISRCTN22012044) to test whether vitamin K supplementation reduced ... randomized 1:1 to vitamin K (menadiol diphosphate 5 mg; n = 45) or placebo (n = 45) thrice weekly. Baseline ...

Abstract	Premature cardiovascular disease and death with a functioning graft are leading causes of death and graft loss, respectively, in kidney transplant recipients (KTRs). Vascular stiffness and calcification are markers of cardiovascular disease that are prevalent in KTR and associated with subclinical vitamin K deficiency. We performed a single-center, phase II, parallel-group, randomized, double-blind, placebo-controlled trial (ISRCTN22012044) to test whether vitamin K supplementation reduced vascular stiffness (MRI-based aortic distensibility) or calcification (coronary artery calcium score on computed tomography) in KTR over 1 year of treatment. The primary outcome was between-group difference in vascular stiffness (ascending aortic distensibility). KTRs were recruited between September 2017 and June 2018, and randomized 1:1 to vitamin K (menadiol diphosphate 5 mg; n = 45) or placebo (n = 45) thrice weekly. Baseline demographics, clinical history, and immunosuppression regimens were similar between groups. There was no impact of vitamin K on vascular stiffness (treatment effect -0.23 [95% CI -0.75 to 0.29] × 10
MeSH term(s)	Dietary Supplements ; Double-Blind Method ; Humans ; Kidney Transplantation/adverse effects ; Vascular Calcification/drug therapy ; Vascular Stiffness ; Vitamin K
Chemical Substances	Vitamin K (12001-79-5)
Language	English
Publishing date	2021-05-02
Publishing country	United States
Document type	Clinical Trial, Phase II ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	2060594-8
ISSN	1600-6143 ; 1600-6135
ISSN (online)	1600-6143
ISSN	1600-6135
DOI	10.1111/ajt.16566
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Article ; Online: Vitamin K Supplementation to Improve Vascular Stiffness in CKD: The K4Kidneys Randomized Controlled Trial.

Journal of the American Society of Nephrology : JASN

2020 Volume 31, Issue 10, Page(s) 2434–2445

Abstract: ... in this patient group. Vitamin K is a cofactor for proteins involved in prevention of vascular calcification ... Whether or not vitamin K supplementation could improve arterial stiffness in patients with CKD is unknown ... Methods: To determine if vitamin K supplementation might improve arterial stiffness in patients in CKD ...

Abstract	Background: Vascular calcification, a risk factor for cardiovascular disease, is common among patients with CKD and is an independent contributor to increased vascular stiffness and vascular risk in this patient group. Vitamin K is a cofactor for proteins involved in prevention of vascular calcification. Whether or not vitamin K supplementation could improve arterial stiffness in patients with CKD is unknown. Methods: To determine if vitamin K supplementation might improve arterial stiffness in patients in CKD, we conducted a parallel-group, double-blind, randomized trial in participants aged 18 or older with CKD stage 3b or 4 (eGFR 15-45 ml/min per 1.73 m Results: We included 159 randomized participants in the modified intention-to-treat analysis, with 80 allocated to receive vitamin K and 79 to receive placebo. Mean age was 66 years, 62 (39%) were female, and 87 (55%) had CKD stage 4. We found no differences in pulse wave velocity at 12 months, augmentation index at 12 months, BP, B-type natriuretic peptide, or physical function. The updated meta-analysis showed no effect of vitamin K supplementation on vascular stiffness or vascular calcification measures. Conclusions: Vitamin K2 supplementation did not improve vascular stiffness or other measures of vascular health in this trial involving individuals with CKD. Clinical trial registry name and registration number: Vitamin K therapy to improve vascular health in patients with chronic kidney disease, ISRCTN21444964 (www.isrctn.com).
MeSH term(s)	Aged ; Dietary Supplements ; Double-Blind Method ; Drug Administration Schedule ; Female ; Humans ; Male ; Middle Aged ; Pulse Wave Analysis ; Renal Insufficiency, Chronic/complications ; Treatment Outcome ; Vascular Calcification/diagnosis ; Vascular Calcification/etiology ; Vascular Calcification/prevention & control ; Vascular Stiffness/drug effects ; Vitamin K 2/therapeutic use ; Vitamins/therapeutic use
Chemical Substances	Vitamins ; Vitamin K 2 (11032-49-8)
Language	English
Publishing date	2020-08-13
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	1085942-1
ISSN	1533-3450 ; 1046-6673
ISSN (online)	1533-3450
ISSN	1046-6673
DOI	10.1681/ASN.2020020225
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Article ; Online: RLP/K enrichment sequencing; a novel method to identify receptor-like protein (RLP) and receptor-like kinase (RLK) genes.

Lin, Xiao / Armstrong, Miles / Baker, Katie / Wouters, Doret / Visser, Richard G F / Wolters, Pieter J / Hein, Ingo / Vleeshouwers, Vivianne G A A

The New phytologist

2020 Volume 227, Issue 4, Page(s) 1264–1276

Abstract: ... Effectoromics leads to precise identification of plants with target PRRs, and subsequent RLP/K enrichment ...

Abstract	The identification of immune receptors in crop plants is time-consuming but important for disease control. Previously, resistance gene enrichment sequencing (RenSeq) was developed to accelerate mapping of nucleotide-binding domain and leucine-rich repeat containing (NLR) genes. However, resistances mediated by pattern recognition receptors (PRRs) remain less utilized. Here, our pipeline shows accelerated mapping of PRRs. Effectoromics leads to precise identification of plants with target PRRs, and subsequent RLP/K enrichment sequencing (RLP/KSeq) leads to detection of informative single nucleotide polymorphisms that are linked to the trait. Using Phytophthora infestans as a model, we identified Solanum microdontum plants that recognize the apoplastic effectors INF1 or SCR74. RLP/KSeq in a segregating Solanum population confirmed the localization of the INF1 receptor on chromosome 12, and led to the rapid mapping of the response to SCR74 to chromosome 9. By using markers obtained from RLP/KSeq in conjunction with additional markers, we fine-mapped the SCR74 receptor to a 43-kbp G-LecRK locus. Our findings show that RLP/KSeq enables rapid mapping of PRRs and is especially beneficial for crop plants with large and complex genomes. This work will enable the elucidation and characterization of the nonNLR plant immune receptors and ultimately facilitate informed resistance breeding.
MeSH term(s)	Amino Acid Sequence ; Phytophthora infestans ; Plant Breeding ; Plant Diseases/genetics ; Receptors, Pattern Recognition ; Solanum
Chemical Substances	Receptors, Pattern Recognition
Language	English
Publishing date	2020-05-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	208885-x
ISSN	1469-8137 ; 0028-646X
ISSN (online)	1469-8137
ISSN	0028-646X
DOI	10.1111/nph.16608
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Book: Practical bioethics

Miles, J.K.

ethics for patients and providers

2023

Author's details	J.K. Miles
Keywords	Medical ethics
Subject code	174.2
Language	English
Size	424 Seiten, Illustrationen, 23 cm
Publisher	Broadview Press
Publishing place	Peterborough, Ontario
Publishing country	Canada
Document type	Book
HBZ-ID	HT030033648
ISBN	978-1-55481-371-1 ; 1-55481-371-9
Database	Catalogue ZB MED Medicine, Health

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2023 A 808	available for loan (reading room)	Lesesaal EG

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Article ; Online: RLP/K enrichment sequencing; a novel method to identify receptor-like protein (RLP) and receptor-like kinase (RLK) genes

Lin, Xiao / Armstrong, Miles / Baker, Katie / Wouters, Doret / Visser, Richard G.F. / Wolters, Pieter J. / Hein, Ingo / Vleeshouwers, Vivianne G.A.A.

New Phytologist

2020 Volume 227, Issue 4

Abstract: ... Effectoromics leads to precise identification of plants with target PRRs, and subsequent RLP/K enrichment ...

Abstract	The identification of immune receptors in crop plants is time-consuming but important for disease control. Previously, resistance gene enrichment sequencing (RenSeq) was developed to accelerate mapping of nucleotide-binding domain and leucine-rich repeat containing (NLR) genes. However, resistances mediated by pattern recognition receptors (PRRs) remain less utilized. Here, our pipeline shows accelerated mapping of PRRs. Effectoromics leads to precise identification of plants with target PRRs, and subsequent RLP/K enrichment sequencing (RLP/KSeq) leads to detection of informative single nucleotide polymorphisms that are linked to the trait. Using Phytophthora infestans as a model, we identified Solanum microdontum plants that recognize the apoplastic effectors INF1 or SCR74. RLP/KSeq in a segregating Solanum population confirmed the localization of the INF1 receptor on chromosome 12, and led to the rapid mapping of the response to SCR74 to chromosome 9. By using markers obtained from RLP/KSeq in conjunction with additional markers, we fine-mapped the SCR74 receptor to a 43-kbp G-LecRK locus. Our findings show that RLP/KSeq enables rapid mapping of PRRs and is especially beneficial for crop plants with large and complex genomes. This work will enable the elucidation and characterization of the nonNLR plant immune receptors and ultimately facilitate informed resistance breeding.
Keywords	Phytophthora infestans ; RLP/K enrichment sequencing (RLP/KSeq) ; RenSeq ; genotyping by sequencing (GBS) ; pattern recognition receptor (PRR) ; potato ; receptor-like kinase (RLK) ; receptor-like protein (RLP)
Subject code	571
Language	English
Publishing country	nl
Document type	Article ; Online
ZDB-ID	208885-x
ISSN	1469-8137 ; 0028-646X
ISSN (online)	1469-8137
ISSN	0028-646X
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Vitamin K for kidney transplant organ recipients: investigating vessel stiffness (ViKTORIES): study rationale and protocol of a randomised controlled trial.

Lees, Jennifer Susan / Mangion, Kenneth / Rutherford, Elaine / Witham, Miles D / Woodward, Rosemary / Roditi, Giles / Hopkins, Tracey / Brooksbank, Katriona / Jardine, Alan G / Mark, Patrick B

Open heart

2020 Volume 7, Issue 2

Abstract: ... calcification inhibitors such as matrix gla protein (MGP) is dependent on vitamin K. RTRs commonly have ... subclinical vitamin K deficiency. The Vitamin K in kidney Transplant Organ Recipients: Investigating vEssel ... Stiffness (ViKTORIES) study assesses whether vitamin K supplementation reduces vascular stiffness and ...

Abstract	Background: Renal transplant recipients (RTRs) exhibit increased vascular stiffness and calcification; these parameters are associated with increased cardiovascular risk. Activity of endogenous calcification inhibitors such as matrix gla protein (MGP) is dependent on vitamin K. RTRs commonly have subclinical vitamin K deficiency. The Vitamin K in kidney Transplant Organ Recipients: Investigating vEssel Stiffness (ViKTORIES) study assesses whether vitamin K supplementation reduces vascular stiffness and calcification in a diverse population of RTR. Methods and analysis: ViKTORIES (ISRCTN22012044) is a single-centre, phase II, parallel-group, randomised, double-blind, placebo-controlled trial of the effect of vitamin K supplementation in 90 prevalent RTR. Participants are eligible if they have a functioning renal transplant for Discussion: This trial may identify a novel, inexpensive and low-risk treatment to improve surrogate markers of cardiovascular risk in RTR.
MeSH term(s)	Aortic Diseases/diagnostic imaging ; Aortic Diseases/etiology ; Aortic Diseases/prevention & control ; Clinical Trials, Phase II as Topic ; Coronary Artery Disease/diagnostic imaging ; Coronary Artery Disease/etiology ; Coronary Artery Disease/prevention & control ; Dietary Supplements/adverse effects ; Double-Blind Method ; Humans ; Kidney Transplantation/adverse effects ; Randomized Controlled Trials as Topic ; Scotland ; Time Factors ; Vascular Calcification/diagnostic imaging ; Vascular Calcification/etiology ; Vascular Calcification/prevention & control ; Vascular Stiffness/drug effects ; Vitamin K/administration & dosage ; Vitamin K/adverse effects ; Vitamin K/analogs & derivatives
Chemical Substances	Vitamin K (12001-79-5) ; menadiol (VQ093653DO)
Language	English
Publishing date	2020-07-16
Publishing country	England
Document type	Clinical Trial Protocol ; Journal Article
ZDB-ID	2747269-3
ISSN	2053-3624
ISSN	2053-3624
DOI	10.1136/openhrt-2019-001070
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Article ; Online: Vitamin K status, supplementation and vascular disease: a systematic review and meta-analysis.

Lees, Jennifer Susan / Chapman, Fiona A / Witham, Miles D / Jardine, Alan G / Mark, Patrick B

Heart (British Cardiac Society)

2018 Volume 105, Issue 12, Page(s) 938–945

Abstract: ... of vascular health associated with cardiovascular events. Vitamin K-dependent proteins (VKDP) are associated ... with VS and VC and require vitamin K for activity. We conducted a systematic review and meta-analysis ... of: (1) the effect of vitamin K supplementation on VS and VC and (2) association of inactive VKDP levels ...

Abstract	Objectives: Vascular stiffness (VS) and vascular calcification (VC) are surrogate markers of vascular health associated with cardiovascular events. Vitamin K-dependent proteins (VKDP) are associated with VS and VC and require vitamin K for activity. We conducted a systematic review and meta-analysis of: (1) the effect of vitamin K supplementation on VS and VC and (2) association of inactive VKDP levels with incident cardiovascular disease and mortality. Methods: Two authors searched MEDLINE and Embase databases and Cochrane and ISRCTN registries for studies of vitamin K clinical trials that measured effects on VC, VS or VKDP and longitudinal studies assessing effect of VKDP on incident CVD or mortality. Random effects meta-analyses were performed. Results: Thirteen controlled clinical trials (n=2162) and 14 longitudinal studies (n=10 726) met prespecified inclusion criteria. Vitamin K supplementation was associated with significant reduction in VC (-9.1% (95% CI -17.7 to -0.5); p=0.04) and VKDP (desphospho-uncarboxylated matrix Gla protein; -44.7% (95% CI -65.1 to -24.3), p<0.0001) and uncarboxylated osteocalcin; -12.0% (95% CI -16.7 to -7.2), p<0.0001) compared with control, with a non-significant improvement in VS. In longitudinal studies with median follow-up of 7.8 (IQR 4.9-11.3) years, VKDP levels were associated with a combined endpoint of CVD or mortality (HR 0.45 (95% CI 0.07 to 0.83), p=0.02). Conclusions: Supplementation with vitamin K significantly reduced VC, but not VS, compared with control. The conclusions drawn are limited by small numbers of studies with substantial heterogeneity. VKDP was associated with combined endpoint of CVD or mortality. Larger clinical trials of effect of vitamin K supplementation to improve VC, VS and long-term cardiovascular health are warranted. Trial registration number: CRD42017060344.
MeSH term(s)	Biomarkers/blood ; Dietary Supplements ; Humans ; Vascular Calcification/blood ; Vascular Calcification/therapy ; Vascular Diseases/blood ; Vascular Diseases/therapy ; Vitamin K/blood ; Vitamin K/pharmacology ; Vitamins/pharmacology
Chemical Substances	Biomarkers ; Vitamins ; Vitamin K (12001-79-5)
Language	English
Publishing date	2018-12-04
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Systematic Review
ZDB-ID	1303417-0
ISSN	1468-201X ; 1355-6037
ISSN (online)	1468-201X
ISSN	1355-6037
DOI	10.1136/heartjnl-2018-313955
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Article ; Online: A lineage-specific rapid diagnostic test (Chagas Sero K-SeT) identifies Brazilian Trypanosoma cruzi II/V/VI reservoir hosts among diverse mammalian orders.

McClean, Mairi C W / Bhattacharyya, Tapan / Mertens, Pascal / Murphy, Niamh / Gilleman, Quentin / Gustin, Yves / Zeippen, Nicolas / Xavier, Samanta C C / Jansen, Ana M / Miles, Michael A

PloS one

2020 Volume 15, Issue 1, Page(s) e0227828

Abstract: ... from diverse Brazilian regions, we apply a novel rapid diagnostic test (RDT, Chagas Sero K-SeT ... of antibodies. Chagas Sero K-SeT RDT results with sera from experimentally infected mice, from tamarin primates ... ELISAs. The Chagas Sero K-Set detected TcII/V/VI infections in Leontopithecus spp. from the Atlantic ...

Abstract	Trypanosoma cruzi, the protozoan agent of Chagas disease in the Americas, is comprised of six genetic lineages (TcI-TcVI) and a possible seventh (TcBat, related to TcI). Identification of T. cruzi lineages infecting reservoir mammalian species is fundamental to resolving transmission cycles. However, this is hindered by the limited sensitivity and technical complexity of parasite isolation and genotyping. An alternative approach is serology using T. cruzi lineage-specific epitopes, such as those of the trypomastigote small surface antigen (TSSA). For surveillance of T. cruzi lineage infections in mammal species from diverse Brazilian regions, we apply a novel rapid diagnostic test (RDT, Chagas Sero K-SeT), which incorporates the TSSA peptide epitope specific to TcII/V/VI (TSSApep-II/V/VI) and Protein G detection of antibodies. Chagas Sero K-SeT RDT results with sera from experimentally infected mice, from tamarin primates (Leontopithecus spp.) and from canines (Canis familiaris) were concordant with corresponding TSSApep-II/V/VI ELISAs. The Chagas Sero K-Set detected TcII/V/VI infections in Leontopithecus spp. from the Atlantic forest (n = 46), in C. familiaris (n = 16) and Thrichomys laurentius (n = 2) from Caatinga biome and Chiroptera (n = 1) from Acre, Amazonia. The Chagas Sero K-SeT RDT is directly applicable to TcII/V/VI-specific serological surveillance of T. cruzi infection in several different mammalian Orders. It can replace ELISAs and provides efficient, point-of-sampling, low-cost detection of TcII/V/VI infections, with at least equivalent sensitivity, although some mammals may be difficult to trap, and, not unexpectedly, Chagas Sero K-SeT could not recognise feline IgG. Knowledge of sylvatic hosts of T. cruzi can be expanded, new reservoir species discovered, and the ecology of transmission cycles clarified, particularly with adaptation to further mammalian Orders.
MeSH term(s)	Animals ; Antigens, Protozoan/blood ; Antigens, Protozoan/immunology ; Brazil/epidemiology ; Cats ; Chagas Disease/blood ; Chagas Disease/diagnosis ; Chagas Disease/veterinary ; Diagnostic Tests, Routine ; Dogs ; Enzyme-Linked Immunosorbent Assay ; Humans ; Mice ; Trypanosoma cruzi/immunology ; Trypanosoma cruzi/isolation & purification
Chemical Substances	Antigens, Protozoan
Language	English
Publishing date	2020-01-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0227828
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Article ; Online: Correction: A lineage-specific rapid diagnostic test (Chagas Sero K-SeT) identifies Brazilian Trypanosoma cruzi II/V/VI reservoir hosts among diverse mammalian orders.

McClean, Mairi C W / Bhattacharyya, Tapan / Mertens, Pascal / Murphy, Niamh / Gilleman, Quentin / Gustin, Yves / Zeippen, Nicolas / Xavier, Samanta C C / Jansen, Ana M / Miles, Michael A

PloS one

2020 Volume 15, Issue 4, Page(s) e0231566

Abstract: This corrects the article DOI: 10.1371/journal.pone.0227828.]. ...

Abstract	[This corrects the article DOI: 10.1371/journal.pone.0227828.].
Language	English
Publishing date	2020-04-02
Publishing country	United States
Document type	Published Erratum
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0231566
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