Renal toxicity of ifosfamide in children with cancer: an exploratory study integrating aldehyde dehydrogenase enzymatic activity data and a wide-array urinary metabolomics approach.
Aldehyde dehydrogenase
Chemotherapy
Childhood cancer
Ifosfamide
Nephrotoxicity
Journal
BMC pediatrics
ISSN: 1471-2431
Titre abrégé: BMC Pediatr
Pays: England
ID NLM: 100967804
Informations de publication
Date de publication:
19 Mar 2024
19 Mar 2024
Historique:
received:
29
09
2023
accepted:
08
02
2024
medline:
20
3
2024
pubmed:
20
3
2024
entrez:
20
3
2024
Statut:
epublish
Résumé
Ifosfamide is a major anti-cancer drug in children with well-known renal toxicity. Understanding the mechanisms underlying this toxicity could help identify children at increased risk of toxicity. The IFOS01 study included children undergoing ifosfamide-based chemotherapy for Ewing sarcoma or rhabdomyosarcoma. A fully evaluation of renal function was performed during and after chemotherapy. Proton nuclear magnetic resonance (NMR) and conventional biochemistry were used to detect early signs of ifosfamide-induced tubulopathy. The enzymatic activity of aldehyde dehydrogenase (ALDH) was measured in the peripheral blood lymphocytes as a marker of ifosfamide-derived chloroacetaldehyde detoxification capacity. Plasma and urine concentrations of ifosfamide and dechloroethylated metabolites were quantified. The 15 participants received a median total ifosfamide dose of 59 g/m Acute renal toxicity was frequent during chemotherapy and did not allow identification of children at risk for long-term toxicity. A role of ALDH in late renal dysfunction is possible so further exploration of its enzymatic activity and polymorphism should be encouraged to improve the understanding of ifosfamide-induced nephrotoxicity.
Sections du résumé
BACKGROUND
BACKGROUND
Ifosfamide is a major anti-cancer drug in children with well-known renal toxicity. Understanding the mechanisms underlying this toxicity could help identify children at increased risk of toxicity.
METHODS
METHODS
The IFOS01 study included children undergoing ifosfamide-based chemotherapy for Ewing sarcoma or rhabdomyosarcoma. A fully evaluation of renal function was performed during and after chemotherapy. Proton nuclear magnetic resonance (NMR) and conventional biochemistry were used to detect early signs of ifosfamide-induced tubulopathy. The enzymatic activity of aldehyde dehydrogenase (ALDH) was measured in the peripheral blood lymphocytes as a marker of ifosfamide-derived chloroacetaldehyde detoxification capacity. Plasma and urine concentrations of ifosfamide and dechloroethylated metabolites were quantified.
RESULTS
RESULTS
The 15 participants received a median total ifosfamide dose of 59 g/m
CONCLUSIONS
CONCLUSIONS
Acute renal toxicity was frequent during chemotherapy and did not allow identification of children at risk for long-term toxicity. A role of ALDH in late renal dysfunction is possible so further exploration of its enzymatic activity and polymorphism should be encouraged to improve the understanding of ifosfamide-induced nephrotoxicity.
Identifiants
pubmed: 38504218
doi: 10.1186/s12887-024-04633-1
pii: 10.1186/s12887-024-04633-1
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
196Subventions
Organisme : Ministère des Affaires Sociales et de la Santé
ID : PHRC 2008
Informations de copyright
© 2024. The Author(s).
Références
Cancer Statistics SEER, Review. 1975–2017, National Cancer Institute. Bethesda, MD. [ https://seer.cancer.gov/csr/1975_2017/ ].
Bhatia S, Sklar C. Second cancers in survivors of childhood cancer. Nat Rev Cancer. 2002;2(2):124–32.
pubmed: 12635175
doi: 10.1038/nrc722
Ehrhardt MJ, Skinner R, Castellino SM. Renal and hepatic Health after Childhood Cancer. Pediatr Clin North Am. 2020;67(6):1203–17.
pubmed: 33131542
doi: 10.1016/j.pcl.2020.07.011
Skinner R, Pearson AD, English MW, Price L, Wyllie RA, Coulthard MG, Craft AW. Risk factors for ifosfamide nephrotoxicity in children. Lancet. 1996;348(9027):578–80.
pubmed: 8774570
doi: 10.1016/S0140-6736(96)03480-0
Rossi R, Ehrich JH. Partial and complete de Toni-Debre-Fanconi syndrome after ifosfamide chemotherapy of childhood malignancy. Eur J Clin Pharmacol. 1993;44(Suppl 1):43–5.
doi: 10.1007/BF01428392
Ruggiero A, Ferrara P, Attina G, Rizzo D, Riccardi R. Renal toxicity and chemotherapy in children with cancer. Br J Clin Pharmacol. 2017;83(12):2605–14.
pubmed: 28758697
pmcid: 5698594
doi: 10.1111/bcp.13388
Norpoth K. Studies on the metabolism of isopnosphamide (NSC-109724) in man. Cancer Treat Rep. 1976;60(4):437–43.
pubmed: 1277219
Dubourg L, Michoudet C, Cochat P, Baverel G. Human kidney tubules detoxify chloroacetaldehyde, a presumed nephrotoxic metabolite of ifosfamide. J Am Soc Nephrol. 2001;12(8):1615–23.
pubmed: 11461933
doi: 10.1681/ASN.V1281615
Dubourg L, Taniere P, Cochat P, Baverel G, Michoudet C. Toxicity of chloroacetaldehyde is similar in adult and pediatric kidney tubules. Pediatr Nephrol. 2002;17(2):97–103.
pubmed: 11875671
doi: 10.1007/s00467-001-0765-2
Boddy AV, English M, Pearson AD, Idle JR, Skinner R. Ifosfamide nephrotoxicity: limited influence of metabolism and mode of administration during repeated therapy in paediatrics. Eur J Cancer. 1996;32A(7):1179–84.
pubmed: 8758250
doi: 10.1016/0959-8049(96)00019-6
Schwartz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL. New equations to estimate GFR in children with CKD. J Am Soc Nephrol. 2009;20(3):629–37.
pubmed: 19158356
pmcid: 2653687
doi: 10.1681/ASN.2008030287
Pierce CB, Munoz A, Ng DK, Warady BA, Furth SL, Schwartz GJ. Age- and sex-dependent clinical equations to estimate glomerular filtration rates in children and young adults with chronic kidney disease. Kidney Int. 2021;99(4):948–56.
pubmed: 33301749
doi: 10.1016/j.kint.2020.10.047
Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract. 2012;120(4):c179–184.
pubmed: 22890468
doi: 10.1159/000339789
Age-based. Pediatric Blood Pressure Reference Charts.
Stevens PE, Levin A, Kidney Disease: Improving Global Outcomes Chronic Kidney Disease Guideline Development Work Group M. Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med. 2013;158(11):825–30.
pubmed: 23732715
doi: 10.7326/0003-4819-158-11-201306040-00007
Skinner R, Sharkey IM, Pearson AD, Craft AW. Ifosfamide, mesna, and nephrotoxicity in children. J Clin Oncol. 1993;11(1):173–90.
pubmed: 8418231
doi: 10.1200/JCO.1993.11.1.173
Nicholson JK, Lindon JC, Holmes E. Metabonomics’: understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data. Xenobiotica. 1999;29(11):1181–9.
pubmed: 10598751
doi: 10.1080/004982599238047
Lever M, Sizeland PC, Bason LM, Hayman CM, Robson RA, Chambers ST. Abnormal glycine betaine content of the blood and urine of diabetic and renal patients. Clin Chim Acta. 1994;230(1):69–79.
pubmed: 7850995
doi: 10.1016/0009-8981(94)90090-6
Pariyani R, Ismail IS, Azam A, Khatib A, Abas F, Shaari K, Hamza H. Urinary metabolic profiling of cisplatin nephrotoxicity and nephroprotective effects of Orthosiphon stamineus leaves elucidated by (1)H NMR spectroscopy. J Pharm Biomed Anal. 2017;135:20–30.
pubmed: 27987392
doi: 10.1016/j.jpba.2016.12.010
Ryu SH, Lee JD, Kim JW, Kim S, Kim S, Kim KB. (1)H NMR toxicometabolomics following cisplatin-induced nephrotoxicity in male rats. J Toxicol Sci. 2019;44(1):57–71.
pubmed: 30626780
doi: 10.2131/jts.44.57
Foxall PJ, Singer JM, Hartley JM, Neild GH, Lapsley M, Nicholson JK, Souhami RL. Urinary proton magnetic resonance studies of early ifosfamide-induced nephrotoxicity and encephalopathy. Clin Cancer Res. 1997;3(9):1507–18.
pubmed: 9815837
Guru SC, Shetty KT. Methodological aspects of aldehyde dehydrogenase assay by spectrophotometric technique. Alcohol. 1990;7(5):397–401.
pubmed: 2222842
doi: 10.1016/0741-8329(90)90022-5
Conjard A, Martin M, Guitton J, Baverel G, Ferrier B. Gluconeogenesis from glutamine and lactate in the isolated human renal proximal tubule: longitudinal heterogeneity and lack of response to adrenaline. Biochem J. 2001;360(Pt 2):371–7.
pubmed: 11716765
pmcid: 1222237
doi: 10.1042/bj3600371
Guitton J, Conjard A, Eid A, Martin M, Boghossian M, Delage H, Baverel G, Ferrier B. Identification of novel targets of cephaloridine in rabbit renal proximal tubules synthesizing glutamine from alanine. Arch Toxicol. 2005;79(10):587–94.
pubmed: 15991025
doi: 10.1007/s00204-005-0673-5
Sottani C, Tranfo G, Faranda P, Minoia C. Highly sensitive high-performance liquid chromatography/selective reaction monitoring mass spectrometry method for the determination of cyclophosphamide and ifosfamide in urine of health care workers exposed to antineoplastic agents. Rapid Commun Mass Spectrom. 2005;19(19):2794–800.
pubmed: 16144038
doi: 10.1002/rcm.2116
Skinner R, Pearson AD, Price L, Coulthard MG, Craft AW. Nephrotoxicity after ifosfamide. Arch Dis Child. 1990;65(7):732–8.
pubmed: 2386379
pmcid: 1792439
doi: 10.1136/adc.65.7.732
English MW, Skinner R, Pearson AD, Price L, Wyllie R, Craft AW. The influence of ifosfamide scheduling on acute nephrotoxicity in children. Br J Cancer. 1997;75(9):1356–9.
pubmed: 9155058
pmcid: 2228242
doi: 10.1038/bjc.1997.229
Rossi R, Pleyer J, Schafers P, Kuhn N, Kleta R, Deufel T, Jurgens H. Development of ifosfamide-induced nephrotoxicity: prospective follow-up in 75 patients. Med Pediatr Oncol. 1999;32(3):177–82.
pubmed: 10064184
doi: 10.1002/(SICI)1096-911X(199903)32:3<177::AID-MPO3>3.0.CO;2-H
Skinner R, Parry A, Price L, Cole M, Craft AW, Pearson AD. Glomerular toxicity persists 10 years after ifosfamide treatment in childhood and is not predictable by age or dose. Pediatr Blood Cancer. 2010;54(7):983–9.
pubmed: 20405516
doi: 10.1002/pbc.22364
Kooijmans EC, Bokenkamp A, Tjahjadi NS, Tettero JM, van Dulmen-den Broeder E, van der Pal HJ, Veening MA. Early and late adverse renal effects after potentially nephrotoxic treatment for childhood cancer. Cochrane Database Syst Rev. 2019;3:CD008944.
pubmed: 30855726
Phillips RS, Tyerman K, Al-Kassim MI, Picton S. A systematic review of the accuracy and utility of early markers of Ifosfamide-induced proximal tubulopathy in survivors of childhood cancers. Pediatr Hematol Oncol. 2008;25(2):107–13.
pubmed: 18363176
doi: 10.1080/08880010701885276
Caron HN, Abeling N, van Gennip A, de Kraker J, Voute PA. Hyperaminoaciduria identifies patients at risk of developing renal tubular toxicity associated with ifosfamide and platinate containing regimens. Med Pediatr Oncol. 1992;20(1):42–7.
pubmed: 1727210
doi: 10.1002/mpo.2950200109
Boudonck KJ, Rose DJ, Karoly ED, Lee DP, Lawton KA, Lapinskas PJ. Metabolomics for early detection of drug-induced kidney injury: review of the current status. Bioanalysis. 2009;1(9):1645–63.
pubmed: 21083109
doi: 10.4155/bio.09.142
Holmes E, Nicholson JK, Nicholls AW, et al. The identification of novel biomarkers of renal toxicity using automatic data reduction techniques and PCA of proton NMR spectra of urine. Chemomet Intel Lab Syst. 1998;44:245–55.
doi: 10.1016/S0169-7439(98)00110-5
Dyck LE. Isoenzymes of aldehyde dehydrogenase in human lymphocytes. Alcohol Clin Exp Res. 1990;14(4):534–8.
pubmed: 2221279
doi: 10.1111/j.1530-0277.1990.tb01195.x
MacAllister SL, Martin-Brisac N, Lau V, Yang K, O’Brien PJ. Acrolein and chloroacetaldehyde: an examination of the cell and cell-free biomarkers of toxicity. Chem Biol Interact. 2013;202(1–3):259–66.
pubmed: 23220588
doi: 10.1016/j.cbi.2012.11.017
Helander A, Johansson B. Inhibition of human erythrocyte and leukocyte aldehyde dehydrogenase activities by diethylthiocarbamic acid methyl ester. An in vivo metabolite of disulfiram. Biochem Pharmacol. 1989;38(13):2195–8.
pubmed: 2735956
doi: 10.1016/0006-2952(89)90076-2
Helander A, Carlsson S. Use of leukocyte aldehyde dehydrogenase activity to monitor inhibitory effect of disulfiram treatment. Alcohol Clin Exp Res. 1990;14(1):48–52.
pubmed: 2178472
doi: 10.1111/j.1530-0277.1990.tb00445.x
Boddy AV, Yule SM, Wyllie R, Price L, Pearson AD, Idle JR. Pharmacokinetics and metabolism of ifosfamide administered as a continuous infusion in children. Cancer Res. 1993;53(16):3758–64.
pubmed: 8339288
Boddy AV, Yule SM, Wyllie R, Price L, Pearson AD, Idle JR. Comparison of continuous infusion and bolus administration of ifosfamide in children. Eur J Cancer. 1995;31A(5):785–90.
pubmed: 7640054
doi: 10.1016/0959-8049(95)00090-6
Silies H, Blaschke G, Hohenlochter B, Rossi R, Jurgens H, Boos J. Excretion kinetics of ifosfamide side-chain metabolites in children on continuous and short-term infusion. Int J Clin Pharmacol Ther. 1998;36(5):246–52.
pubmed: 9629987
Kerbusch T, de Kraker J, Keizer HJ, van Putten JW, Groen HJ, Jansen RL, Schellens JH, Beijnen JH. Clinical pharmacokinetics and pharmacodynamics of ifosfamide and its metabolites. Clin Pharmacokinet. 2001;40(1):41–62.
pubmed: 11236809
doi: 10.2165/00003088-200140010-00004
Children’s Oncology Group. Long-term Follow-Up guidelines for survivors of Childhood, adolescent, and Young Adult Cancers. In. vol. Version 5.0; 2018.
Skinner R, Pearson AD, Coulthard MG, Skillen AW, Hodson AW, Goldfinch ME, Gibb I, Craft AW. Assessment of chemotherapy-associated nephrotoxicity in children with cancer. Cancer Chemother Pharmacol. 1991;28(2):81–92.
pubmed: 2060086
doi: 10.1007/BF00689694
Skinner R, Pearson AD, Craft AW. Ifosfamide nephrotoxicity in children. Med Pediatr Oncol. 1994;22(2):153–4.
pubmed: 8259103
doi: 10.1002/mpo.2950220219
Skinner R. Late renal toxicity of treatment for childhood malignancy: risk factors, long-term outcomes, and surveillance. Pediatr Nephrol. 2018;33(2):215–25.
pubmed: 28434047
doi: 10.1007/s00467-017-3662-z