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Aminoaciduria in the prediction of ifosfamide-induced tubulopathy after childhood cancer: a feasibility study

BACKGROUND: Ifosfamide, an alkylating agent used widely in the treatment of childhood malignancy, can cause many side effects including a proximal tubulopathy. Studies suggest that aminoaciduria is seen most commonly of all the biochemical abnormalities of ifosfamide-induced tubulopathy. A recent sy...

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Autores principales: Morgan, Jessica E., McKeever, Karl, Tyerman, Kay S., Henderson, Michael, Picton, Susan, Phillips, Robert S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5154030/
https://www.ncbi.nlm.nih.gov/pubmed/27965825
http://dx.doi.org/10.1186/s40814-015-0040-0
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author Morgan, Jessica E.
McKeever, Karl
Tyerman, Kay S.
Henderson, Michael
Picton, Susan
Phillips, Robert S.
author_facet Morgan, Jessica E.
McKeever, Karl
Tyerman, Kay S.
Henderson, Michael
Picton, Susan
Phillips, Robert S.
author_sort Morgan, Jessica E.
collection PubMed
description BACKGROUND: Ifosfamide, an alkylating agent used widely in the treatment of childhood malignancy, can cause many side effects including a proximal tubulopathy. Studies suggest that aminoaciduria is seen most commonly of all the biochemical abnormalities of ifosfamide-induced tubulopathy. A recent systematic review has found a paucity of data regarding the value of early markers indicating clinically significant tubulopathy. We undertook a pilot study to determine the feasibility of examining whether patients can be risk-stratified on the basis of aminoaciduria for the development of future significant ifosfamide-induced tubulopathy, to allow the evolution of appropriate follow-up strategies. We also aimed to define accrual rates, costs and clinical demands for a future larger study. METHODS: This observational study recruited 21 patients from the Leeds Paediatric Oncology service. The medical notes of each patient were reviewed for demographic and clinical data. Simultaneous samples of blood and urine were obtained. RESULTS: The investigations in the feasibility study were acceptable to patients and were minimally demanding on both clinical and laboratory staff. Financially, the cost per patient was minimal. This study was not powered to detect significant associations with TmP/GFR (ratio of renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate), growth and electrolyte supplementation. However, all patients with minimal aminoaciduria (≤2 elevated urinary amino acids) had normal TmP/GFR and no need for electrolyte supplementation. CONCLUSIONS: This pilot study has shown that a larger study is feasible and may provide clinically useful data to change current practice. This should aim to establish whether the number of abnormal amino acids or the degree of abnormality is most significant in predicting clinically significant proximal tubulopathy.
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spelling pubmed-51540302016-12-13 Aminoaciduria in the prediction of ifosfamide-induced tubulopathy after childhood cancer: a feasibility study Morgan, Jessica E. McKeever, Karl Tyerman, Kay S. Henderson, Michael Picton, Susan Phillips, Robert S. Pilot Feasibility Stud Research BACKGROUND: Ifosfamide, an alkylating agent used widely in the treatment of childhood malignancy, can cause many side effects including a proximal tubulopathy. Studies suggest that aminoaciduria is seen most commonly of all the biochemical abnormalities of ifosfamide-induced tubulopathy. A recent systematic review has found a paucity of data regarding the value of early markers indicating clinically significant tubulopathy. We undertook a pilot study to determine the feasibility of examining whether patients can be risk-stratified on the basis of aminoaciduria for the development of future significant ifosfamide-induced tubulopathy, to allow the evolution of appropriate follow-up strategies. We also aimed to define accrual rates, costs and clinical demands for a future larger study. METHODS: This observational study recruited 21 patients from the Leeds Paediatric Oncology service. The medical notes of each patient were reviewed for demographic and clinical data. Simultaneous samples of blood and urine were obtained. RESULTS: The investigations in the feasibility study were acceptable to patients and were minimally demanding on both clinical and laboratory staff. Financially, the cost per patient was minimal. This study was not powered to detect significant associations with TmP/GFR (ratio of renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate), growth and electrolyte supplementation. However, all patients with minimal aminoaciduria (≤2 elevated urinary amino acids) had normal TmP/GFR and no need for electrolyte supplementation. CONCLUSIONS: This pilot study has shown that a larger study is feasible and may provide clinically useful data to change current practice. This should aim to establish whether the number of abnormal amino acids or the degree of abnormality is most significant in predicting clinically significant proximal tubulopathy. BioMed Central 2016-01-22 /pmc/articles/PMC5154030/ /pubmed/27965825 http://dx.doi.org/10.1186/s40814-015-0040-0 Text en © Morgan et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Morgan, Jessica E.
McKeever, Karl
Tyerman, Kay S.
Henderson, Michael
Picton, Susan
Phillips, Robert S.
Aminoaciduria in the prediction of ifosfamide-induced tubulopathy after childhood cancer: a feasibility study
title Aminoaciduria in the prediction of ifosfamide-induced tubulopathy after childhood cancer: a feasibility study
title_full Aminoaciduria in the prediction of ifosfamide-induced tubulopathy after childhood cancer: a feasibility study
title_fullStr Aminoaciduria in the prediction of ifosfamide-induced tubulopathy after childhood cancer: a feasibility study
title_full_unstemmed Aminoaciduria in the prediction of ifosfamide-induced tubulopathy after childhood cancer: a feasibility study
title_short Aminoaciduria in the prediction of ifosfamide-induced tubulopathy after childhood cancer: a feasibility study
title_sort aminoaciduria in the prediction of ifosfamide-induced tubulopathy after childhood cancer: a feasibility study
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5154030/
https://www.ncbi.nlm.nih.gov/pubmed/27965825
http://dx.doi.org/10.1186/s40814-015-0040-0
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