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High-dose methotrexate (HD-MTX) is commonly used in treatment of pediatric leukemias and lymphomas. Transient deterioration in renal function is frequently noted during HD-MTX treatment, but possible long-term changes are less well known. In this study we aimed to study long-term renal prognosis after HD-MTX treatment, and to find possible underlying risk factors for reduced renal function.Medical records of pediatric cancer patients treated with HD-MTX were reviewed retrospectively after follow-up of 1–10 years. Renal function before and after chemotherapy was investigated in a total of 28 patients. Assessment of glomerular and tubular function was prospectively evaluated in each case. Glomerular function was evaluated by either 51Cr-EDTA or 99mTc-DTPA clearance methods, and by urinary albumin excretion. Tubular function was assessed by measuring blood electrolyte levels and urinary α1- or β2-microglobulin.A decrease in glomerular filtration rate (GFR) was statistically significant as follow-up time increased (P = 0.02). Age at the time of diagnosis and exposure to potentially nephrotoxic antibiotics during cancer treatment had no influence on GFR. However, albuminuria was observed more often in patients treated with amphotericin B or gentamycin (P = 0.04). No changes in tubular function were observed.Our results show that HD-MTX treatment significantly decreases GFR and may cause albuminuria in pediatric cancer patients several years after treatment. Long-term renal follow-up of these patients is therefore important. Pediatr Blood Cancer 2008;51:535–539. © 2008 Wiley-Liss, Inc.