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  1. Article ; Online: Traditional and disease-related cardiovascular risk factors in ANCA-associated vasculitis: A prospective, two-centre cohort study.

    Vegting, Yosta / Penne, Erik L / Hilhorst, Marc L / Hoekstra, Tiny / Bemelman, Frederike J / Vogt, Liffert / Voskuyl, Alexandre E / Pagnoux, Christian / Houben, Eline

    Joint bone spine

    2023  Volume 90, Issue 4, Page(s) 105540

    Abstract: Objectives: ANCA-associated vasculitis (AAV) has been associated with increased risk of cardiovascular (CV) events. The aim was to assess traditional and disease-related CV risk determinants in a two-centre prospective cohort of AAV patients.: Methods! ...

    Abstract Objectives: ANCA-associated vasculitis (AAV) has been associated with increased risk of cardiovascular (CV) events. The aim was to assess traditional and disease-related CV risk determinants in a two-centre prospective cohort of AAV patients.
    Methods: Patients were recruited from centres in the Netherlands and Canada. A comprehensive CV risk assessment was performed at inclusion. Subjects were followed up yearly for 3-5 years until the first CV event, death or end of follow-up. Cox proportional hazards analyses were performed to relate baseline characteristics to the first CV event.
    Results: A total of 144 patients were included (mean age 62 years, female sex 44%, median Framingham risk score 14.3%). Insulin resistance was present in 73% of patients tested at inclusion, independent of concurrent prednisone therapy. After a median follow-up of 2.90 years, 16 patients (11%) experienced a CV event (14 non-fatal and 2 fatal). The incidence of CV events was 5.45 per 100 patient-years. Age, Framingham risk score, HbA1c level, Diabetes Mellitus (DM), and previous CV event were significantly associated with CV events. Other factors, such as sex, impaired renal function, dyslipidemia, hypertension, smoking history and microalbuminuria, or disease-specific variables, like ANCA serotype or disease activity, were not significantly related to CV events in univariable or age-adjusted cox regression analysis.
    Conclusions: Determinants of an increased CV risk were identified. Disease-related factors and treatments can further modify individual risk factors, such as for steroids causing chronic insulin resistance and DM. Treatment of risk factors is essential to optimize long-term outcomes in AAV patients.
    MeSH term(s) Humans ; Female ; Middle Aged ; Risk Factors ; Cardiovascular Diseases/epidemiology ; Cardiovascular Diseases/etiology ; Cohort Studies ; Prospective Studies ; Insulin Resistance ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/epidemiology ; Diabetes Mellitus/epidemiology ; Heart Disease Risk Factors
    Language English
    Publishing date 2023-02-08
    Publishing country France
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2020487-5
    ISSN 1778-7254 ; 1297-319X
    ISSN (online) 1778-7254
    ISSN 1297-319X
    DOI 10.1016/j.jbspin.2023.105540
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Alkaline phosphatase treatment of acute kidney injury - an update.

    Steenvoorden, Thei S / Rood, Janneke A J / Bemelman, Frederike J / Armstrong-Jr, Roberto / Leuvenink, Henri G D / van der Heijden, Joost W / Vogt, Liffert

    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

    2024  

    Abstract: Through improved insight in the increasing incidence and detrimental effects of acute kidney injury (AKI), its clinical relevance has become more and more apparent. Although treatment strategies for AKI have also somewhat improved, an adequate remedy ... ...

    Abstract Through improved insight in the increasing incidence and detrimental effects of acute kidney injury (AKI), its clinical relevance has become more and more apparent. Although treatment strategies for AKI have also somewhat improved, an adequate remedy still does not exist. Finding one is complicated by a multifactorial pathophysiology and by heterogeneity in the patient population. Alkaline phosphatase (AP) has been suggested as a therapy for sepsis-associated AKI because of its protective effects against lipopolysaccharide (LPS) induced inflammation and kidney injury in animals. However, translation of these protective effects into tangible clinical benefit has proven difficult. Because the anti-inflammatory properties of AP are likely not reliant on a direct effect on LPS itself, we postulate that other pathways are much more important in explaining the renoprotective properties ascribed to AP. The reevaluation of which properties of the AP enzyme are responsible for the benefit seen in the lab, is an important step to determine where the true potential of AP as a treatment strategy for AKI in the clinic lies. In this review, we will discuss how AP can prevent activation of harmful pro-inflammatory receptors, redirect cell-cell signaling, and protect barrier tissues, which together form the basis for current knowledge of the role of AP in the kidney. With this knowledge in mind and by analyzing currently available clinical evidence, we propose directions for new research that can determine whether AP as a treatment strategy for AKI has a future in the clinical field.
    Language English
    Publishing date 2024-02-23
    Publishing country England
    Document type Journal Article
    ZDB-ID 90594-x
    ISSN 1460-2385 ; 0931-0509
    ISSN (online) 1460-2385
    ISSN 0931-0509
    DOI 10.1093/ndt/gfae028
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: The effect of genetic variants in the transcription factor TSPYL family on the CYP3A4 mediated cyclosporine metabolism in kidney transplant patients.

    Zhai, Qinglian / Moes, Dirk Jan A R / van Gelder, Teun / van der Lee, Maaike / Sanders, Jan-Stephan / Bemelman, Frederike J / de Fijter, Johan W / Klein, Kathrin / Schwab, Matthias / Swen, Jesse J

    Clinical and translational science

    2024  Volume 17, Issue 2, Page(s) e13729

    Abstract: CYP3A4 activity shows considerable interindividual variability. Although studies indicate 60%-80% is heritable, common single nucleotide variants (SNVs) in CYP3A4 together only explain ~10%. Transcriptional factors, such as the testis-specific Y-encoded- ... ...

    Abstract CYP3A4 activity shows considerable interindividual variability. Although studies indicate 60%-80% is heritable, common single nucleotide variants (SNVs) in CYP3A4 together only explain ~10%. Transcriptional factors, such as the testis-specific Y-encoded-like proteins (TSPYLs) family, have been reported to regulate the expression of CYP enzymes including CYP3A4 in vitro. Here, we investigated the effect of genetic variants in TSPYL on CYP3A4 activity using data from a clinical study and a human liver bank. Five SNVs (rs3828743, rs10223646, rs6909133, rs1204807, and rs1204811) in TSPYL were selected because of a reported effect on CYP3A4 expression in vitro or suggested clinical effect. For the clinical study, whole blood concentrations, clinical data, and DNA were available from 295 kidney transplant recipients participating in the prospective MECANO study. A multivariate pharmacokinetic model adjusted for body weight, steroid treatment, and CYP3A4 genotype was used to assess the effect of the genetic variants on cyclosporine clearance. In multivariate analysis, homozygous carriers of rs3828743 had a 18% lower cyclosporin clearance compared to the wild-type and heterozygous patients (28.72 vs. 35.03 L/h, p = 0.018) indicating a lower CYP3A4 activity and an opposite direction of effect compared to the previously reported increased CYP3A4 expression. To validate, we tested associations between rs3828743 and CYP3A4 mRNA and protein expression as well as enzyme activity with data from a liver bank (n = 150). No association with any of these end points was observed. In conclusion, the totality of evidence is not in support of a significant role for TSPYL SNV rs3828743 in explaining variability in CYP3A4 activity.
    MeSH term(s) Male ; Humans ; Cyclosporine/pharmacokinetics ; Cytochrome P-450 CYP3A/genetics ; Immunosuppressive Agents/pharmacokinetics ; Transcription Factors/genetics ; Kidney Transplantation/adverse effects ; Prospective Studies ; Genotype ; Polymorphism, Single Nucleotide
    Chemical Substances Cyclosporine (83HN0GTJ6D) ; Cytochrome P-450 CYP3A (EC 1.14.14.1) ; Immunosuppressive Agents ; Transcription Factors ; CYP3A4 protein, human (EC 1.14.14.55)
    Language English
    Publishing date 2024-02-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2433157-0
    ISSN 1752-8062 ; 1752-8054
    ISSN (online) 1752-8062
    ISSN 1752-8054
    DOI 10.1111/cts.13729
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Plasma Exchange Therapy Using Solvent Detergent-Treated Plasma: An Observational Pilot Study on Complement, Neutrophil and Endothelial Cell Activation in a Case Series of Patients Suffering from Atypical Hemolytic Uremic Syndrome.

    de Wit, Yasmin / Rethans, Arne / van Mierlo, Gerard / Wouters, Diana / Ten Brinke, Anja / Bemelman, Frederike J / Zeerleder, Sacha

    Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie

    2022  Volume 49, Issue 5, Page(s) 288–297

    Abstract: Introduction: Plasma exchange therapy (PEX) was standard treatment for thrombotic microangiopathy before eculizumab was available and is still widely applied. However, most PEX patients still ultimately progress to end-stage renal disease (ESRD). It has ...

    Abstract Introduction: Plasma exchange therapy (PEX) was standard treatment for thrombotic microangiopathy before eculizumab was available and is still widely applied. However, most PEX patients still ultimately progress to end-stage renal disease (ESRD). It has been suggested that infusion of plasma that contains active complement may induce additional complement activation with subsequent activation of neutrophils and endothelial cells, leading to exacerbation of organ damage and deterioration of renal function.
    Objective: This observational pilot study examines the effect of hemodialysis, eculizumab and PEX before and after treatment in plasma of aHUS patients on complement-, neutrophil and endothelial cell activation.
    Methods: Eleven patients were included in this pilot study. Six patients were treated with hemodialysis, 2 patients received regular infusions of eculizumab, and 3 patients were on a regular schedule for PEX. Patients were followed during 3 consecutive treatments. Blood samples were taken before and after patients received their treatment.
    Results: Complement activation products increased in plasma of patients after PEX, as opposed to patients treated with hemodialysis or eculizumab. Increased levels of complement activation products were detected in omniplasma used for PEX. Additionally, activation of neutrophils and endothelial cells was observed in patients after hemodialysis and PEX, but not in patients receiving eculizumab treatment.
    Conclusion: In this pilot study we observed that PEX induced complement and neutrophil activation, and that omniplasma contains significant amounts of complement activation products. Additionally, we demonstrate that hemodialysis induces activation of neutrophils and endothelial cells. Complement activation with subsequent neutrophil activation may contribute to the deterioration of organ function and may result in ESRD. Further randomized controlled studies are warranted to investigate the effect of PEX on complement- and neutrophil activation in patients with thrombotic microangiopathy.
    Language English
    Publishing date 2022-03-25
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2100848-6
    ISSN 1660-3818 ; 1660-3796
    ISSN (online) 1660-3818
    ISSN 1660-3796
    DOI 10.1159/000522137
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: IL-10-Secreting CD8

    Jackson, Sarah E / Sedikides, George X / Romashova, Veronika / Okecha, Georgina / Remmerswaal, Ester B M / Bemelman, Frederike J / Sinclair, John H / Wills, Mark R

    Pathogens (Basel, Switzerland)

    2022  Volume 11, Issue 12

    Abstract: HCMV-specific ... ...

    Abstract HCMV-specific CD8
    Language English
    Publishing date 2022-12-13
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2695572-6
    ISSN 2076-0817
    ISSN 2076-0817
    DOI 10.3390/pathogens11121530
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  6. Article ; Online: A failing kidney and a burning tongue.

    Bemelman, Frederike J / Verhoeven, Christine L

    Kidney international

    2014  Volume 86, Issue 3, Page(s) 654

    MeSH term(s) Adult ; Humans ; Hypertension/etiology ; Kidney Failure, Chronic/complications ; Kidney Failure, Chronic/surgery ; Kidney Transplantation ; Male ; Stomatitis/etiology ; Taste Disorders/etiology ; Tongue Diseases/etiology
    Language English
    Publishing date 2014-09
    Publishing country United States
    Document type Case Reports ; Journal Article
    ZDB-ID 120573-0
    ISSN 1523-1755 ; 0085-2538
    ISSN (online) 1523-1755
    ISSN 0085-2538
    DOI 10.1038/ki.2013.533
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  7. Article ; Online: Prophylactic and early outpatient treatment of COVID-19 in patients with kidney disease: considerations from the Immunonephrology Working Group of the European Renal Association (ERA-IWG).

    Hilhorst, Marc / Bemelman, Frederike J / Bruchfeld, Annette / Fernandez-Juarez, Gema M / Floege, Jürgen / Frangou, Eleni / Goumenos, Dimitrios / van Kooten, Cees / Kronbichler, Andreas / Stevens, Kate I / Turkmen, Kultigin / Wiersinga, W Joost / Anders, Hans-Joachim

    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

    2023  Volume 38, Issue 8, Page(s) 1807–1816

    Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic led to rapid vaccine development and large global vaccination schemes. However, patients with immune-mediated kidney disease, chronic kidney diseases and kidney transplant ... ...

    Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic led to rapid vaccine development and large global vaccination schemes. However, patients with immune-mediated kidney disease, chronic kidney diseases and kidney transplant recipients show high non-response rates to vaccination despite more than three vaccinations and, consequently, reduced viral clearance capacity when infected while receiving certain immunosuppressants, carrying an elevated risk for coronavirus disease 2019 (COVID-19)-related morbidity and mortality. SARS-CoV-2 evolution has been characterized by the emergence of novel variants and spike mutations contributing to waning efficacy of neutralizing antibodies. To this end, the therapeutic field expands from vaccination towards a combined approach of immunization, pre-exposure prophylaxis and early post-exposure treatment using direct-acting antivirals and neutralizing monoclonal antibodies to treat early in the disease course and avoid hospitalization. This expert opinion paper from the Immunonephrology Working Group of the European Renal Association (ERA-IWG) summarizes available prophylactic and/or early treatment options (i.e. neutralizing monoclonal antibodies and direct-acting antivirals) of SARS-CoV-2-infected patients with immune-mediated kidney disease, chronic kidney disease and kidney transplant recipients.
    MeSH term(s) Humans ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Neutralizing/therapeutic use ; Antibodies, Viral ; Antiviral Agents/therapeutic use ; COVID-19/prevention & control ; Outpatients ; Renal Insufficiency, Chronic/complications ; SARS-CoV-2 ; Vaccination
    Chemical Substances Antibodies, Monoclonal ; Antibodies, Neutralizing ; Antibodies, Viral ; Antiviral Agents
    Language English
    Publishing date 2023-03-31
    Publishing country England
    Document type Journal Article
    ZDB-ID 90594-x
    ISSN 1460-2385 ; 0931-0509
    ISSN (online) 1460-2385
    ISSN 0931-0509
    DOI 10.1093/ndt/gfad044
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Alkaline phosphatase to treat ischaemia-reperfusion injury in living-donor kidney transplantation: APhIRI I feasibility pilot study.

    Steenvoorden, Thei S / van Duin, Robert E / Rood, Janneke A J / Peters-Sengers, Hessel / Nurmohamed, Azam S / Bemelman, Frederike J / Vogt, Liffert / van der Heijden, Joost W

    British journal of clinical pharmacology

    2023  Volume 89, Issue 12, Page(s) 3629–3636

    Abstract: Aims: Ischemia-reperfusion injury (IRI) during kidney transplant procedures is associated with adverse outcome. Alkaline phosphatase (AP) is an enzyme that has the potential to dampen IRI. Prior to this study, it had not been tested in the setting of ... ...

    Abstract Aims: Ischemia-reperfusion injury (IRI) during kidney transplant procedures is associated with adverse outcome. Alkaline phosphatase (AP) is an enzyme that has the potential to dampen IRI. Prior to this study, it had not been tested in the setting of kidney transplantation. This study aimed to evaluate the safety and feasibility of peri-procedural AP administration in living donor kidney transplantation.
    Methods: In this double blind, randomized, placebo-controlled, single-center pilot study, all eligible recipients of living donor kidneys were asked to give informed consent. AP (bRESCAP) or a placebo was administered intravenously over 24 hours after the transplantation procedure. The primary outcome-graft function at 1 year-was represented by iohexol measured glomerular filtration rate (mGFR). Serum and urine biomarkers within seven days after surgery were used as surrogate markers of kidney function and injury.
    Results: Eleven patients were enrolled of whom five were treated with bRESCAP and six with placebo. After 1 year, mGFR was not different between groups. No specific adverse events were observed in the bRESCAP group. Urine expression of injury biomarkers CCL14, NGAL and Cystatin C was lower in the bRESCAP group at day seven. This was statistically significant.
    Conclusion: This study illustrates that bRESCAP treatment is feasible in kidney transplantation, might have a dampening effect on IRI induced renal inflammation, and raises no safety concerns. Future research will evaluate the effects of bRESCAP treatment in donation after circulatory death kidney transplantation where IRI is more pronounced.
    MeSH term(s) Humans ; Kidney Transplantation/adverse effects ; Alkaline Phosphatase ; Pilot Projects ; Living Donors ; Feasibility Studies ; Kidney ; Reperfusion Injury/etiology ; Biomarkers
    Chemical Substances Alkaline Phosphatase (EC 3.1.3.1) ; Biomarkers
    Language English
    Publishing date 2023-08-16
    Publishing country England
    Document type Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 188974-6
    ISSN 1365-2125 ; 0306-5251 ; 0264-3774
    ISSN (online) 1365-2125
    ISSN 0306-5251 ; 0264-3774
    DOI 10.1111/bcp.15871
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  9. Article ; Online: The Use of the Oxygenated AirdriveTM Machine Perfusion System in Kidney Graft Preservation: A Clinical Pilot Study.

    Houtzager, Julia H E / Hemelrijk, Sebastiaan David / Post, Ivo C J H / Idu, Mirza M / Bemelman, Frederike J / van Gulik, Thomas M

    European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes

    2021  Volume 61, Issue 6, Page(s) 153–162

    Abstract: Background: The shortage of donor kidneys has led to the use of marginal donors, e.g., those whose kidneys are donated after circulatory death. Preservation of the graft by hypothermic machine perfusion (HMP) provides a viable solution to reduce warm ... ...

    Abstract Background: The shortage of donor kidneys has led to the use of marginal donors, e.g., those whose kidneys are donated after circulatory death. Preservation of the graft by hypothermic machine perfusion (HMP) provides a viable solution to reduce warm ischemic damage. This pilot study was undertaken to assess the feasibility and patient safety of the AirdriveTM HMP system in clinical kidney transplantation.
    Methods: Five deceased-donor kidneys were preserved using the oxygenated Airdrive HMP system between arrival at the recipient center (Amsterdam UMC) and implantation in the patient. The main study end-points were adverse effects due to the use of Airdrive HMP. Secondary end-points were clinical outcomes and perfusion parameters. All events occurring during the transplantation procedure or within 1 month of follow-up were monitored.
    Results: Five patients were included in this pilot study. No technical failures were observed during the preservation period using the Airdrive HMP. Mean perfusion parameters were: duration 8.5 h (3-15 h), pressure 25 mm Hg (18-25 mm Hg), flow 49.77 mL/min (19-58 mL/min), resistance 0.57 mm Hg/min/mL (0.34-1.3 mm Hg/min/mL), and temperature 8.2 °C (2-13°C). Mean cold ischemia time (CIT) was 20.2 h (11-29.5 h). No adverse events or technical failures were observed during preservation and transplantation or during the 1-month follow-up.
    Conclusions: This pilot study showed the feasibility of the use of the Airdrive HMP system with no adverse events in clinical kidney transplantation.
    MeSH term(s) Adult ; Aged ; Feasibility Studies ; Female ; Humans ; Kidney ; Kidney Transplantation ; Male ; Middle Aged ; Organ Preservation/instrumentation ; Perfusion/instrumentation ; Perfusion/statistics & numerical data ; Pilot Projects ; Transplants ; Young Adult
    Language English
    Publishing date 2021-02-18
    Publishing country Switzerland
    Document type Clinical Study ; Journal Article
    ZDB-ID 205700-1
    ISSN 1421-9921 ; 0014-312X
    ISSN (online) 1421-9921
    ISSN 0014-312X
    DOI 10.1159/000513493
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  10. Article ; Online: Monocytes and macrophages in ANCA-associated vasculitis.

    Vegting, Yosta / Vogt, Liffert / Anders, Hans-Joachim / de Winther, Menno P J / Bemelman, Frederike J / Hilhorst, Marc L

    Autoimmunity reviews

    2021  Volume 20, Issue 10, Page(s) 102911

    Abstract: Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) are characterized by inflammation of small-to-medium-sized blood vessels and the presence of autoantibodies against cytoplasmic proteases sited in neutrophils and monocytes. ... ...

    Abstract Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) are characterized by inflammation of small-to-medium-sized blood vessels and the presence of autoantibodies against cytoplasmic proteases sited in neutrophils and monocytes. Increasing evidence indicates a substantial role of monocytes and macrophages in the pathogenesis of AAV. Activated monocytes and macrophages contribute to necroinflammation in peripheral vasculitic lesions as well as to central and peripheral mechanisms of autoimmunity. The intermediate monocyte subset (CD14
    MeSH term(s) Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis ; Antibodies, Antineutrophil Cytoplasmic ; Humans ; Macrophages ; Monocytes ; Neutrophils ; Phagocytosis
    Chemical Substances Antibodies, Antineutrophil Cytoplasmic
    Language English
    Publishing date 2021-07-20
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 2144145-5
    ISSN 1873-0183 ; 1568-9972
    ISSN (online) 1873-0183
    ISSN 1568-9972
    DOI 10.1016/j.autrev.2021.102911
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