title: Long-term evaluation of Ifosfamide-related nephrotoxicity in children.
abstract: OBJECTIVE
  Ifosfamide is widely used in pediatric oncology but its nephrotoxicity may become a significant issue in survivors. This study is aimed at evaluating the incidence of late renal toxicity of ifosfamide and its risk factors.
  
  
  METHODS
  Of the 183 patients prospectively investigated for renal function, 77 treated for rhabdomyosarcoma, 39 for other soft tissue sarcoma, 39 for Ewing's sarcoma, and 28 for osteosarcoma were investigated at least 5 years after treatment. No patients had received cisplatin and/or carboplatin. Glomerular and tubular functions were graded according to the Skinner system.
  
  
  RESULTS
  The median dose of ifosfamide was 54 g/m(2) (range, 18 to 117 g/m(2)). After a median follow-up of 10 years, 89.5% of patients had normal tubular function, and 78.5% had normal glomerular function rate (GFR). Serum bicarbonate and calcium were normal in all patients. Hypomagnesemia was observed in 1.2% and hypophosphatemia in 1%. The tubular threshold for phosphate was reduced in 24% of the patients (grade 1 in 15%, grade 2 in 8%, and grade 3 in 0.5%). Glycosuria was detected in 37% of the patients but was more than 0.5 g/24 hours in only 5%. Proteinuria was observed in 12%. Ifosfamide dose and interval from therapy to investigations were predictors of tubulopathy in univariate and multivariate analysis. In a multivariate analysis, an older age at diagnosis and the length of interval since treatment had independent impacts on the risk of abnormal GFR.
  
  
  CONCLUSIONS
  Renal toxicity is moderate with a moderate dose of ifosfamide. However, since it can be permanent and can get worse with time, repeated long-term evaluations are important, and this risk should be balanced against efficacy.
authors.affiliation: Pediatrics and Biostatistics Departments, and l'Institut National de la Santé et de la Recherche Médicale, Institut Gustave Roussy, Villejuif, France. oberlin@igr.fr
authors.forename: Odile
authors.initials: O
authors.lastname: Oberlin
authors.forename: Oumaya
authors.initials: O
authors.lastname: Fawaz
authors.forename: Annie
authors.initials: A
authors.lastname: Rey
authors.forename: Patrick
authors.initials: P
authors.lastname: Niaudet
authors.forename: Vita
authors.initials: V
authors.lastname: Ridola
authors.forename: Daniel
authors.initials: D
authors.lastname: Orbach
authors.forename: Christophe
authors.initials: C
authors.lastname: Bergeron
authors.forename: Annie Sophie
authors.initials: AS
authors.lastname: Defachelles
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Gentet
authors.forename: Claudine
authors.initials: C
authors.lastname: Schmitt
authors.forename: Hervé
authors.initials: H
authors.lastname: Rubie
authors.forename: Martine
authors.initials: M
authors.lastname: Munzer
authors.forename: Dominique
authors.initials: D
authors.lastname: Plantaz
authors.forename: Anne
authors.initials: A
authors.lastname: Deville
authors.forename: Veronique
authors.initials: V
authors.lastname: Minard
authors.forename: Nadège
authors.initials: N
authors.lastname: Corradini
authors.forename: Guy
authors.initials: G
authors.lastname: Leverger
authors.forename: Florent
authors.initials: F
authors.lastname: de Vathaire
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use; D002648:Child; D005500:Follow-Up Studies; D006801:Humans; D007069:Ifosfamide / Q000009:adverse effects* / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology; D007677:Kidney Function Tests; D015999:Multivariate Analysis; D012516:Osteosarcoma / Q000188:drug therapy; D011446:Prospective Studies; D012044:Regression Analysis; D012208:Rhabdomyosarcoma / Q000188:drug therapy; D012307:Risk Factors; D012509:Sarcoma / Q000188:drug therapy; D012512:Sarcoma, Ewing / Q000188:drug therapy; D013997:Time Factors
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007069:Ifosfamide