title: Assessment of renal function during high-dose methotrexate treatment in children with acute lymphoblastic leukemia.
abstract: BACKGROUND
  High-dose methotrexate (HD-MTX) is potentially nephrotoxic. The feasibility of novel biomarkers to indicate renal injury due to HD-MTX infusion was studied in children with acute lymphoblastic leukemia (ALL).
  
  
  METHODS
  Markers for glomerular and tubular injury were evaluated prospectively after HD-MTX infusion in 20 children with ALL. Plasma creatinine, cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL) were measured 24-48 hr before MTX-infusion and 24, 36, 48, and 72 hr after starting the HD-MTX treatment, and thereafter daily until the MTX concentration was below 0.1 µmol/L. Urine NGAL, β2 -microglobulin, and creatinine concentrations as well as dipstick and urinalysis were performed at the same time points.
  
  
  RESULTS
  In children with ALL, HD-MTX treatment at 5 g/m(2) over 24 hr was well tolerated and none of the patients developed significant glomerular or tubular dysfunction. The mean plasma cystatin C level increased significantly (P < 0.001) from 0.83 mg/L at baseline to 0.94 mg/L at 36 hr after starting the HD-MTX treatment. The cystatin C concentration remained within reference range in all but two patients (10%). There was no significant change in plasma creatinine level during or after HD-MTX treatment, the values being normal in all patients. Plasma and urea NGAL did not increase during or after the HD-MTX treatment.
  
  
  CONCLUSIONS
  Our results suggest that plasma cystatin C concentration alone is a sensitive marker to monitor renal function during and after HD-MTX infusion in pediatric ALL patients. Plasma or urine NGAL do not provide any further advantage in the follow-up of these patients.
authors.affiliation: Central Hospital and Helsinki University, Helsinki, Finland.
authors.forename: Elisa
authors.initials: E
authors.lastname: Ylinen
authors.forename: Kirsi
authors.initials: K
authors.lastname: Jahnukainen
authors.forename: Ulla M
authors.initials: UM
authors.lastname: Saarinen-Pihkala
authors.forename: Timo
authors.initials: T
authors.lastname: Jahnukainen
mesh_terms: D000209:Acute-Phase Proteins / Q000652:urine; D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000652:urine; D055316:Cystatin C / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007677:Kidney Function Tests; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000652:urine; D001613:beta 2-Microglobulin / Q000652:urine
chemical_list: D000209:Acute-Phase Proteins; D000964:Antimetabolites, Antineoplastic; D015415:Biomarkers; D055316:Cystatin C; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D001613:beta 2-Microglobulin; D003404:Creatinine; D008727:Methotrexate
keywords: NGAL; acute lymphoblastic leukemia; children; cystatin C; high-dose methotrexate; renal function