Ifosfamide nephrotoxicity in pediatric cancer patients

Abstract

The renal functions in pediatric cancer patients who received ifosfamide (IFO) treatment were evaluated and the risk factors related to IFO nephrotoxicity were determined. The medical records of all children treated with IFO were reviewed, and 62 with normal renal function before IFO treatment were selected. Nephrotoxicity was diagnosed by measuring urine beta2-microglobulin and glucose, and serum phosphate, bicarbonate, and creatinine. Forty-eight (77.4%) had a history of previous cisplatin treatment. Nephrotoxicity was detected in 20 patients (32.3%). beta2-Microglobulinuria was observed in all 20, hypophosphatemia in 10 (16.1%), hypocarbia in 2 (3.2%), glucosuria in 5 (8.1%), and decreased creatinine clearance in 7 (11.3%). The cumulative dose of IFO and a history of previous cisplatin therapy were related to nephrotoxicity. Among the 20 patients with nephrotoxicity, the median cumulative dose of IFO in patients with a low (<500 mg/m2) and high (>500 mg/m2) cumulative dose of previous cisplatin was 80 g/m2 (73-102 g/m2) and 45 g/m2 (11-76 g/m2), respectively. Most of the nephrotoxicity persisted after cessation of IFO treatment. In conclusion, close monitoring of IFO nephrotoxicity should be started earlier in patients with high-dose cisplatin pretreatment. Tubular proteinuria, as indicated by beta2-microglobulinuria, was the most-sensitive marker for IFO nephrotoxicity. Long-term follow-up study for reversibility of IFO nephrotoxicity is in progress.

A Systematic Review of the Accuracy and Utility of Early Markers of Ifosfamide-Induced Proximal Tubulopathy in Survivors of Childhood Cancers

“…Ifosfamide-induced renal toxicity is well described and often presents as proximal renal tubular dysfunction and/or reduction in glomerular filtration rate in the long term, which can result in chronic renal failure [1]. Acute proximal renal tubular dysfunction is well described during treatment and the majority of cases resolve after completion of chemotherapy.…”

Side Effects of Ifosfamide

“…cisplatin or aminoglycoside antibiotics), young age and higher cumulative dose of ifosfamide [4]. In contrast to hemorrhagic cystitis, mesna cannot overcome ifosfamide-induced nephrotoxicity and most of it persists after cessation of ifosfamide treatment [5]. Simultaneous administration of cisplatin appears to increase the risk of delayed or persistent renal tubular dysfunction, while concomitant use of carboplatin seems to induce more frequently acute tubulopathy, in comparison with ifosfamide alone [6].…”

Genitourinary long-term outcomes for childhood cancer survivors

“…Nephrogenic diabetes insipidus secondary to severe distal tubular toxicity is rare [12]. Risk factors for ifosfamide-induced nephrotoxicity are high cumulative ifosfamide dose, concomitant cisplatin therapy, and unilateral nephrectomy [13][14][15].…”