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Association of mineral and bone biomarkers with adverse cardiovascular outcomes and mortality in the German Chronic Kidney Disease(GCKD)cohort

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Bone Research 2023年第4期11卷 764-771页

作者： katharina charlotte reimer Jennifer Nadal Heike Meiselbach Matthias Schmid Ulla T.Schultheiss Fruzsina Kotsis Helena Stockmann Nele Friedrich Matthias Nauck Vera Krane Kai-Uwe Eckardt Markus P.Schneider Rafael Kramann Jürgen Floege Turgay Saritas Department of Nephrology Rheumatologyand Clinical ImmunologyUniversity Hospital RWTH AachenAachenGermany Institute of Experimental Medicine and Systems Biology RWTH Aachen UniversityAachenGermany Institute for Cell and Tumor Biology RWTH Aachen UniversityAachenGermany Institute of Medical Biometry Informatics and EpidemiologyUniversity Hospital of BonnBonnGermany Department of Nephrology and Hypertension University of Erlangen-NürnbergErlangenGermany Institute of Genetic Epidemiology Faculty of Medicine and Medical Center-University of FreiburgFreiburgGermany Department of Medicine IV-Nephrology and Primary Care Faculty of Medicine and Medical Center-University of FreiburgFreiburgGermany Department of Nephrology and Medical Intensive Care Charité-Universitätsmedizin BerlinBerlinGermany Department of Nephrology University Medical Center RegensburgRegensburgGermany Institute of Clinical Chemistry and Laboratory Medicine University Medicine GreifswaldGreifswaldGermany DZHK(German Centre for Cardiovascular Research) Partner Site GreifswaldUniversity MedicineGreifswaldGermany Department of Medicine I Division of NephrologyUniversity Hospital WürzburgWürzburgGermany

Mineral and bone disorder(MBD)in chronic kidney disease(CKD)is tightly linked to cardiovascular disease(CVD).In this study,we aimed to compare the prognostic value of nine MBD biomarkers to determine those associated best with adverse cardiovascular(CV)outcomes and mortality.In 5217 participants of the German CKD(GCKD)study enrolled with an estimated glomerular filtration rate(eG FR)between 30–60 mL·min-1 per 1.73 m2 or overt proteinuria,serum osteoprotegerin(OPG),C-terminal fibroblast growth factor-23(FGF23),intact parathyroid hormone(iP TH),bone alkaline phosphatase(BAP),cross-linked C-telopeptide of type 1 collagen(CTX1),procollagen 1intact N-terminal propeptide(P1NP),phosphate,calcium,and 25-OH vitamin D were measured at baseline.Participants with missing values among these parameters(n=971)were excluded,leaving a total of 4246 participants for analysis.During a median follow-up of6.5 years,387 non-CV deaths,173 CV deaths,645 nonfatal major adverse CV events(MACEs)and 368 hospitalizations for congestive heart failure(CHF)were observed.OPG and FGF23 were associated with all outcomes,with the highest hazard ratios(HRs)for OPG.In the final Cox regression model,adjusted for CV risk factors,including kidney function and all other investigated biomarkers,each standard deviation increase in OPG was associated with non-CV death(HR 1.76,95%CI:1.35–2.30),CV death(HR 2.18,95%CI:1.50–3.16),MACE(HR 1.38,95%CI:1.12–1.71)and hospitalization for CHF(HR 2.05,95%CI:1.56–2.69).Out of the nine biomarkers examined,stratification based on serum OPG best identified the CKD patients who were at the highest risk for any adverse CV outcome and mortality.

关键词： Kidney cardiovascular vitamin

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Safety,immunogenicity,and protection provided by unadjuvanted and adjuvanted formulations of a recombinant plant-derived virus-like particle vaccine candidate for COVID-19 in nonhuman primates

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Cellular & Molecular Immunology 2022年第2期19卷 222-233页

作者： Stéphane Pillet Prabhu SArunachalam Guadalupe Andreani Nadia Golden Jane Fontenot Pyone Pyone Aye katharina Röltgen Gabrielle Lehmicke Philipe Gobeil charlotte Dubé Sonia Trépanier Nathalie Charland Marc-AndréD’Aoust Kasi Russell-Lodrigue Christopher Monjure Robert V.Blair Scott D.Boyd Rudolf P.Bohm Jay Rappaport François Villinger Nathalie Landry Bali Pulendran Brian J.Ward Medicago Inc. QuébecQCCanada. Institute for Immunity Transplantation and InfectionStanford University School of MedicineStanford UniversityStanfordCAUSA. Tulane National Primate Research Center CovingtonLAUSA. New Iberia Research Center University of Louisiana at LafayetteNew IberiaLAUSA. Department of Pathology Stanford University School of MedicineStanford UniversityStanfordCAUSA. Department of Microbiology and Immunology Tulane University School of MedicineNew OrleansLAUSA. Department of Microbiology and Immunology Stanford University School of MedicineStanford UniversityStanfordCAUSA. Institute for Immunity Transplantation&InfectionStanford University School of MedicineStanford UniversityStanfordCAUSA Research Institute of the McGill University Health Centre MontrealQCCanada.

Although antivirals are important tools to control severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection,effective vaccines are essential to control the current coronavirus disease 2019(COVID-19)pandemic.Plant-derived virus-like particle(VLP)vaccine candidates have previously demonstrated immunogenicity and efficacy against influenza.Here,we report the immunogenicity and protection induced in rhesus macaques by intramuscular injections of a VLP bearing a SARS-CoV-2 spike protein(CoVLP)vaccine candidate formulated with or without Adjuvant System 03(AS03)or cytidine-phospho-guanosine(CpG)1018.Although a single dose of the unadjuvanted CoVLP vaccine candidate stimulated humoral and cell-mediated immune responses,booster immunization(at 28 days after priming)and adjuvant administration significantly improved both responses,with higher immunogenicity and protection provided by the AS03-adjuvanted CoVLP.Fifteen micrograms of CoVLP adjuvanted with AS03 induced a polyfunctional interleukin-2(IL-2)-driven response and IL-4 expression in CD4 T cells.Animals were challenged by multiple routes(i.e.,intratracheal,intranasal,and ocular)with a total viral dose of 106 plaque-forming units of SARS-CoV-2.Lower viral replication in nasal swabs and bronchoalveolar lavage fluid(BALF)as well as fewer SARS-CoV-2-infected cells and immune cell infiltrates in the lungs concomitant with reduced levels of proinflammatory cytokines and chemotactic factors in the BALF were observed in animals immunized with the CoVLP adjuvanted with AS03.No clinical,pathologic,or virologic evidence of vaccineassociated enhanced disease was observed in vaccinated animals.The CoVLP adjuvanted with AS03 was therefore selected for vaccine development and clinical trials.

关键词： SARS-CoV-2 Virus-like particles Non-humane primates AS03 CpG1018

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