Assessment of renal function during high-dose methotrexate treatment in children with acute lymphoblastic leukemia

Pediatr Blood Cancer. 2014 Dec;61(12):2199-202. doi: 10.1002/pbc.25137. Epub 2014 Aug 31.


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).

Procedure: 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.

Keywords: NGAL; acute lymphoblastic leukemia; children; cystatin C; high-dose methotrexate; renal function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / urine
  • Adolescent
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Biomarkers / analysis*
  • Child
  • Child, Preschool
  • Creatinine / urine
  • Cystatin C / blood*
  • Dose-Response Relationship, Drug
  • Feasibility Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Kidney Function Tests
  • Lipocalin-2
  • Lipocalins / urine
  • Male
  • Methotrexate / therapeutic use*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Prognosis
  • Prospective Studies
  • Proto-Oncogene Proteins / urine
  • beta 2-Microglobulin / urine


  • Acute-Phase Proteins
  • Antimetabolites, Antineoplastic
  • Biomarkers
  • Cystatin C
  • LCN2 protein, human
  • Lipocalin-2
  • Lipocalins
  • Proto-Oncogene Proteins
  • beta 2-Microglobulin
  • Creatinine
  • Methotrexate