Abstract
BackgroundIfosfamide, 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.MethodsThis 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.ResultsThe 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.ConclusionsThis 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.
Highlights
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 the most frequently detected abnormality in tubular dysfunction and may be a good early predictor of long-term ifosfamide-induced tubulopathy [7]
This review found that urinary β2 macroglobulin might be useful in a similar way, with low levels suggesting a low risk of significant tubulopathy and high levels identifying patients at higher risk who require more intense follow-up
Summary
Ifosfamide, an alkylating agent used widely in the treatment of childhood malignancy, can cause many side effects including a proximal 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. Ifosfamide is an alkylating agent that is used widely for the treatment of malignancies, including those seen in children. Ifosfamide can cause many immediate and some long-lasting side effects, including a proximal tubulopathy and renal impairment [1]. Studies suggest that aminoaciduria is the most frequently detected abnormality in tubular dysfunction and may be a good early predictor of long-term ifosfamide-induced tubulopathy [7]. The presence of aminoaciduria is due to an impairment of the mechanisms which would normally result in the reabsorption of amino acids from the filtrate in the proximal tubule [3]
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