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

Jessica E Morgan; Karl McKeever; Kay S Tyerman; Michael Henderson; Susan Picton; Robert S Phillips

doi:10.1186/s40814-015-0040-0

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

Jessica E Morgan, Karl McKeever, Kay S Tyerman, Michael Henderson, Susan Picton, Robert S Phillips

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Number of pages	6
Journal	Pilot and Feasibility Studies
Volume	2
Issue number	4
DOIs	https://doi.org/10.1186/s40814-015-0040-0
Publication status	Published - 22 Jan 2016

Keywords

Journal Article

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10.1186/s40814-015-0040-0

Cite this

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

abstract = "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.",

keywords = "Journal Article",

author = "Morgan, {Jessica E} and Karl McKeever and Tyerman, {Kay S} and Michael Henderson and Susan Picton and Phillips, {Robert S}",

year = "2016",

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T1 - Aminoaciduria in the prediction of ifosfamide-induced tubulopathy after childhood cancer

T2 - a feasibility study

AU - Morgan, Jessica E

AU - McKeever, Karl

AU - Tyerman, Kay S

AU - Henderson, Michael

AU - Picton, Susan

AU - Phillips, Robert S

PY - 2016/1/22

Y1 - 2016/1/22

N2 - 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.

AB - 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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