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Glomerular toxicity persists 10 years after ifosfamide treatment in childhood and is not predictable by age or dose
Author(s) -
Skinner Roderick,
Parry Annie,
Price Lisa,
Cole Michael,
Craft Alan W.,
Pearson Andrew D.J.
Publication year - 2010
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.22364
Subject(s) - nephrotoxicity , medicine , ifosfamide , renal function , urology , toxicity , prospective cohort study , cumulative dose , gastroenterology , surgery , chemotherapy , cisplatin
Background This prospective longitudinal single institution cohort study evaluated the natural history of and risk factors for chronic nephrotoxicity 10 years after ifosfamide treatment in childhood. Procedure Twenty‐five patients (16 males) treated with ifosfamide were investigated at end of treatment (End), 1 and 10 years later. Glomerular filtration rate (GFR), serum phosphate (PO 4 ) and bicarbonate (HCO 3 ) and renal tubular threshold for phosphate (Tm p /GFR) were measured, and total nephrotoxicity score (N s ) graded. Results More patients had a low GFR at 1 (72%) and 10 (50%) years than at End (26%) ( P = 0.006 for End vs. 1 year). Electrolyte supplementation requirements for tubular toxicity resolved by 10 years (0% vs. 32% at End and 24% at 1 year; both P < 0.05). At 10 years, 17% of patients had moderate overall nephrotoxicity and 13% clinically significant reduction of GFR (<60 ml/min/1.73 m 2 ). Neither dose nor age at treatment predicted any measure of toxicity at 10 years or reduced GFR at any timepoint. Higher cumulative ifosfamide dose correlated with greater tubular and overall nephrotoxicity at End and/or 1 year ( P < 0.05 for each of PO 4 , HCO 3 , Tm p /GFR, N s ), but age at treatment did not differ between patients with normal or abnormal results. Conclusions Although clinically significant tubular toxicity had resolved by 10 years, GFR was <60 ml/min/1.73 m 2 in 13% of patients, raising concerns about very long‐term glomerular function. Higher cumulative dose was associated with greater tubular and overall toxicity at End and 1 year, but not at 10 years. Age at treatment did not predict nephrotoxicity at any timepoint. Pediatr Blood Cancer 2010;54:983–989 © 2010 Wiley‐Liss, Inc.