Mechanism-Based Urinary Biomarkers to Identify the Potential for Aminoglycoside-Induced Nephrotoxicity in Premature Neonates: A Proof-of-Concept Study
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{"title"=>"Mechanism-based urinary biomarkers to identify the potential for aminoglycoside-induced nephrotoxicity in premature neonates: A proof-of-concept study", "type"=>"journal", "authors"=>[{"first_name"=>"Stephen J.", "last_name"=>"McWilliam", "scopus_author_id"=>"36102760600"}, {"first_name"=>"Daniel J.", "last_name"=>"Antoine", "scopus_author_id"=>"24390766700"}, {"first_name"=>"Venkata", "last_name"=>"Sabbisetti", "scopus_author_id"=>"8863835000"}, {"first_name"=>"Mark A.", "last_name"=>"Turner", "scopus_author_id"=>"8968212100"}, {"first_name"=>"Tracey", "last_name"=>"Farragher", "scopus_author_id"=>"15062873200"}, {"first_name"=>"Joseph V.", "last_name"=>"Bonventre", "scopus_author_id"=>"7102330952"}, {"first_name"=>"B. Kevin", "last_name"=>"Park", "scopus_author_id"=>"35478124100"}, {"first_name"=>"Rosalind L.", "last_name"=>"Smyth", "scopus_author_id"=>"7102358057"}, {"first_name"=>"Munir", "last_name"=>"Pirmohamed", "scopus_author_id"=>"7006669713"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"365489844", "sgr"=>"84865287291", "issn"=>"19326203", "pmid"=>"22937100", "scopus"=>"2-s2.0-84865287291", "doi"=>"10.1371/journal.pone.0043809", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"9a3f5f88-890a-3ae1-8483-cc8976d74d82", "abstract"=>"Premature infants are frequently exposed to aminoglycoside antibiotics. Novel urinary biomarkers may provide a non-invasive means for the early identification of aminoglycoside-related proximal tubule renal toxicity, to enable adjustment of treatment and identification of infants at risk of long-term renal impairment. In this proof-of-concept study, urine samples were collected from 41 premature neonates (≤ 32 weeks gestation) at least once per week, and daily during courses of gentamicin, and for 3 days afterwards. Significant increases were observed in the three urinary biomarkers measured (Kidney Injury Molecule-1 (KIM-1), Neutrophil Gelatinase-associated Lipocalin (NGAL), and N-acetyl-β-D-glucosaminidase (NAG)) during treatment with multiple courses of gentamicin. When adjusted for potential confounders, the treatment effect of gentamicin remained significant only for KIM-1 (mean difference from not treated, 1.35 ng/mg urinary creatinine; 95% CI 0.05-2.65). Our study shows that (a) it is possible to collect serial urine samples from premature neonates, and that (b) proximal tubule specific urinary biomarkers can act as indicators of aminoglycoside-associated nephrotoxicity in this age group. Further studies to investigate the clinical utility of novel urinary biomarkers in comparison to serum creatinine need to be undertaken.", "link"=>"http://www.mendeley.com/research/mechanismbased-urinary-biomarkers-identify-potential-aminoglycosideinduced-nephrotoxicity-premature", "reader_count"=>34, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Researcher"=>7, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>3, "Other"=>3, "Student > Master"=>6, "Student > Bachelor"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Researcher"=>7, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>3, "Other"=>3, "Student > Master"=>6, "Student > Bachelor"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Environmental Science"=>1, "Medicine and Dentistry"=>17, "Agricultural and Biological Sciences"=>8, "Neuroscience"=>1, "Veterinary Science and Veterinary Medicine"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>2, "Business, Management and Accounting"=>1, "Physics and Astronomy"=>1, "Chemistry"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>17}, "Neuroscience"=>{"Neuroscience"=>1}, "Chemistry"=>{"Chemistry"=>2}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>8}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Environmental Science"=>{"Environmental Science"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>2}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"United States"=>1, "United Kingdom"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/587250"], "description"=>"<p>Representative figures demonstrating the longitudinal quantification of the biomarkers KIM-1 (blue; ng/mg. uCr), NGAL (green; ng/mg. uCr), NAG (yellow; IU/mg. uCr) and serum creatinine (red; µmol/L) for three infants treated with gentamicin (A–C). Gentamicin treatment episode and length of treatment (days) are indicated by the black horizontal bar on each figure for that individual patient.</p>", "links"=>[], "tags"=>["biomarker", "infants", "treated", "courses", "gentamicin", "serum", "creatinine"], "article_id"=>257728, "categories"=>["Cell Biology", "Biochemistry", "Marine Biology", "Medicine", "Pharmacology"], "users"=>["Stephen J. McWilliam", "Daniel J. Antoine", "Venkata Sabbisetti", "Mark A. Turner", "Tracey Farragher", "Joseph V. Bonventre", "B. Kevin Park", "Rosalind L. Smyth", "Munir Pirmohamed"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0043809.g002", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Longitudinal_biomarker_analysis_of_infants_treated_with_multiple_courses_of_gentamicin_without_a_change_in_serum_creatinine_concentration_/257728", "title"=>"Longitudinal biomarker analysis of infants treated with multiple courses of gentamicin without a change in serum creatinine concentration.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 00:25:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/587115"], "description"=>"<p>Representative figures demonstrating the longitudinal quantification of the biomarkers KIM-1 (blue; ng/mg. uCr), NGAL (green; ng/mg. uCr), NAG (yellow; IU/mg. uCr) and serum creatinine (red; µmol/L) for three infants treated with gentamicin (A–C). Gentamicin treatment episode and length of treatment (days) are indicated by the black horizontal bar on each figure for that individual patient.</p>", "links"=>[], "tags"=>["biomarker", "infants", "treated", "courses", "gentamicin", "serum", "creatinine"], "article_id"=>257589, "categories"=>["Cell Biology", "Biochemistry", "Marine Biology", "Medicine", "Pharmacology"], "users"=>["Stephen J. McWilliam", "Daniel J. Antoine", "Venkata Sabbisetti", "Mark A. Turner", "Tracey Farragher", "Joseph V. Bonventre", "B. Kevin Park", "Rosalind L. Smyth", "Munir Pirmohamed"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0043809.g001", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Longitudinal_biomarker_analysis_of_infants_treated_with_multiple_courses_of_gentamicin_with_a_change_in_serum_creatinine_concentration_AKI_/257589", "title"=>"Longitudinal biomarker analysis of infants treated with multiple courses of gentamicin with a change in serum creatinine concentration (AKI).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 00:24:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/587403"], "description"=>"<p>The mean baseline biomarker values in the absence of any gentamicin treatment were 1.91 ng/mg uCr (95% CI 1.07, 2.76) for KIM-1, 0.13 IU/mg uCr (0.07, 0.19) for NAG, 425.4 ng/mg uCr (162.6, 688.3) for NGAL, and 62.39 µmol/l (53.1, 71.69) for creatinine.</p>", "links"=>[], "tags"=>["gentamicin", "biomarker"], "article_id"=>257893, "categories"=>["Cell Biology", "Biochemistry", "Marine Biology", "Medicine", "Pharmacology"], "users"=>["Stephen J. McWilliam", "Daniel J. Antoine", "Venkata Sabbisetti", "Mark A. Turner", "Tracey Farragher", "Joseph V. Bonventre", "B. Kevin Park", "Rosalind L. Smyth", "Munir Pirmohamed"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0043809.t002", "stats"=>{"downloads"=>5, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Association_between_gentamicin_treatment_and_the_change_in_biomarker_values_/257893", "title"=>"Association between gentamicin treatment and the change in biomarker values.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 00:26:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/587363"], "description"=>"<p>Patients are subdivided according to gestational age. Mean biomarker values presented include samples collected both on and off gentamicin treatment over the whole time course of inclusion in the study.</p>", "links"=>[], "tags"=>["characteristics", "signs", "neonates", "treated"], "article_id"=>257847, "categories"=>["Cell Biology", "Biochemistry", "Marine Biology", "Medicine", "Pharmacology"], "users"=>["Stephen J. McWilliam", "Daniel J. Antoine", "Venkata Sabbisetti", "Mark A. Turner", "Tracey Farragher", "Joseph V. Bonventre", "B. Kevin Park", "Rosalind L. Smyth", "Munir Pirmohamed"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0043809.t001", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Baseline_characteristics_and_clinical_signs_of_neonates_treated_with_gentamicin_/257847", "title"=>"Baseline characteristics and clinical signs of neonates treated with gentamicin.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 00:26:17"}

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  • {"unique-ip"=>"4", "full-text"=>"2", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
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Relative Metric

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