Exposure to an Extended-Interval, High-Dose Gentamicin Regimen in the Neonatal Period Is Not Associated With Long-Term Nephrotoxicity

Objectives: To assess the association between gentamicin exposure and subclinical signs of nephrotoxicity in school children who were exposed to a high-dose gentamicin regimen in the neonatal period.Methods: Children receiving three or more doses (6 mg/kg) of gentamicin as neonates were invited to a...

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Autores principales:	Veronika Rypdal, Sondre Jørandli, Dagny Hemmingsen, Marit Dahl Solbu, Claus Klingenberg
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	gentamicin exposure neonates subclinical nephrotoxicity urine biomarkers chronic kidney disease Pediatrics RJ1-570
Acceso en línea:	https://doaj.org/article/6650195d685f4baab01cccf74bd07458
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spelling	oai:doaj.org-article:6650195d685f4baab01cccf74bd074582021-12-01T18:23:26ZExposure to an Extended-Interval, High-Dose Gentamicin Regimen in the Neonatal Period Is Not Associated With Long-Term Nephrotoxicity2296-236010.3389/fped.2021.779827https://doaj.org/article/6650195d685f4baab01cccf74bd074582021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fped.2021.779827/fullhttps://doaj.org/toc/2296-2360Objectives: To assess the association between gentamicin exposure and subclinical signs of nephrotoxicity in school children who were exposed to a high-dose gentamicin regimen in the neonatal period.Methods: Children receiving three or more doses (6 mg/kg) of gentamicin as neonates were invited to a follow-up in school age. We evaluated potential signs of subclinical nephrotoxicity with four validated urine biomarkers: protein-creatinine ratio (PCR), albumin-creatinine ratio (ACR), kidney injury molecule-1 (KIM-1), and N-acetyl-beta-D-glucosaminidase (NAG) normalized for urine creatinine (NAG-Cr). In addition, blood pressure was measured. The measures of gentamicin exposure were cumulative dose (mg/kg) and highest trough plasma concentration (TPC) in mg/L. We used logistic and linear regression and non-parametric kernel regression to analyze the relationship between gentamicin exposure and the urine biomarkers.Results: A total of 222 gentamicin exposed children were included. As neonates, the children were exposed to a median (interquartile range-IQR) cumulative gentamicin dose of 36 (26–42) mg/kg and the median (IQR) TPC was 1.0 (0.7–1.3) mg/L. At follow-up, 15 children (6.8%) had either one abnormal urine biomarker value (13 children) or two abnormal urine biomarker values (2 children). These 17 biomarker values were all marginally above the suggested upper cutoff, and included the following markers; KIM-1 (n = 2), NAC-Cr (n = 5), ACR (n = 6), and PCR (n = 4). All other 207 children had normal sets of all four urine biomarkers. One child had hypertension. There were no differences in gentamicin exposure, gestational age (GA) at birth or birth weight between the group of 15 children with one or two abnormal urine biomarker values compared to the other 207 children who had normal biomarker values. Using different regression analyses, we did not find any association between gentamicin exposure (cumulative dose and/or TPC) and the urine biomarker values.Conclusions: Exposure to an extended-interval, high-dose gentamicin regimen in the neonatal period was not associated with signs of subclinical nephrotoxicity in schoolchildren. We therefore suggest that the gentamicin treatment regimen evaluated in this study is safe in terms of long-term nephrotoxicity.Clinical Trial Registration:ClinicalTrials.gov, identifier: NCT03253614.Veronika RypdalVeronika RypdalSondre JørandliDagny HemmingsenDagny HemmingsenMarit Dahl SolbuMarit Dahl SolbuClaus KlingenbergClaus KlingenbergFrontiers Media S.A.articlegentamicin exposureneonatessubclinical nephrotoxicityurine biomarkerschronic kidney diseasePediatricsRJ1-570ENFrontiers in Pediatrics, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	gentamicin exposure neonates subclinical nephrotoxicity urine biomarkers chronic kidney disease Pediatrics RJ1-570
spellingShingle	gentamicin exposure neonates subclinical nephrotoxicity urine biomarkers chronic kidney disease Pediatrics RJ1-570 Veronika Rypdal Veronika Rypdal Sondre Jørandli Dagny Hemmingsen Dagny Hemmingsen Marit Dahl Solbu Marit Dahl Solbu Claus Klingenberg Claus Klingenberg Exposure to an Extended-Interval, High-Dose Gentamicin Regimen in the Neonatal Period Is Not Associated With Long-Term Nephrotoxicity
description	Objectives: To assess the association between gentamicin exposure and subclinical signs of nephrotoxicity in school children who were exposed to a high-dose gentamicin regimen in the neonatal period.Methods: Children receiving three or more doses (6 mg/kg) of gentamicin as neonates were invited to a follow-up in school age. We evaluated potential signs of subclinical nephrotoxicity with four validated urine biomarkers: protein-creatinine ratio (PCR), albumin-creatinine ratio (ACR), kidney injury molecule-1 (KIM-1), and N-acetyl-beta-D-glucosaminidase (NAG) normalized for urine creatinine (NAG-Cr). In addition, blood pressure was measured. The measures of gentamicin exposure were cumulative dose (mg/kg) and highest trough plasma concentration (TPC) in mg/L. We used logistic and linear regression and non-parametric kernel regression to analyze the relationship between gentamicin exposure and the urine biomarkers.Results: A total of 222 gentamicin exposed children were included. As neonates, the children were exposed to a median (interquartile range-IQR) cumulative gentamicin dose of 36 (26–42) mg/kg and the median (IQR) TPC was 1.0 (0.7–1.3) mg/L. At follow-up, 15 children (6.8%) had either one abnormal urine biomarker value (13 children) or two abnormal urine biomarker values (2 children). These 17 biomarker values were all marginally above the suggested upper cutoff, and included the following markers; KIM-1 (n = 2), NAC-Cr (n = 5), ACR (n = 6), and PCR (n = 4). All other 207 children had normal sets of all four urine biomarkers. One child had hypertension. There were no differences in gentamicin exposure, gestational age (GA) at birth or birth weight between the group of 15 children with one or two abnormal urine biomarker values compared to the other 207 children who had normal biomarker values. Using different regression analyses, we did not find any association between gentamicin exposure (cumulative dose and/or TPC) and the urine biomarker values.Conclusions: Exposure to an extended-interval, high-dose gentamicin regimen in the neonatal period was not associated with signs of subclinical nephrotoxicity in schoolchildren. We therefore suggest that the gentamicin treatment regimen evaluated in this study is safe in terms of long-term nephrotoxicity.Clinical Trial Registration:ClinicalTrials.gov, identifier: NCT03253614.
format	article
author	Veronika Rypdal Veronika Rypdal Sondre Jørandli Dagny Hemmingsen Dagny Hemmingsen Marit Dahl Solbu Marit Dahl Solbu Claus Klingenberg Claus Klingenberg
author_facet	Veronika Rypdal Veronika Rypdal Sondre Jørandli Dagny Hemmingsen Dagny Hemmingsen Marit Dahl Solbu Marit Dahl Solbu Claus Klingenberg Claus Klingenberg
author_sort	Veronika Rypdal
title	Exposure to an Extended-Interval, High-Dose Gentamicin Regimen in the Neonatal Period Is Not Associated With Long-Term Nephrotoxicity
title_short	Exposure to an Extended-Interval, High-Dose Gentamicin Regimen in the Neonatal Period Is Not Associated With Long-Term Nephrotoxicity
title_full	Exposure to an Extended-Interval, High-Dose Gentamicin Regimen in the Neonatal Period Is Not Associated With Long-Term Nephrotoxicity
title_fullStr	Exposure to an Extended-Interval, High-Dose Gentamicin Regimen in the Neonatal Period Is Not Associated With Long-Term Nephrotoxicity
title_full_unstemmed	Exposure to an Extended-Interval, High-Dose Gentamicin Regimen in the Neonatal Period Is Not Associated With Long-Term Nephrotoxicity
title_sort	exposure to an extended-interval, high-dose gentamicin regimen in the neonatal period is not associated with long-term nephrotoxicity
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/6650195d685f4baab01cccf74bd07458
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Exposure to an Extended-Interval, High-Dose Gentamicin Regimen in the Neonatal Period Is Not Associated With Long-Term Nephrotoxicity

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