Partial and complete de Toni-Debré-Fanconi syndrome after ifosfamide chemotherapy of childhood malignancy

Abstract

Ten out of 79 patients treated with ifosfamide (IFO) developed a complete (n = 2) or partial (n = 8) de Toni-Debré-Fanconi syndrome (RFS). All but one of these patients had been treated in addition with cisplatinum (CPL) or had undergone radiotherapy to the abdomen or nephrectomy as part of the overall treatment for malignancy. A detailed nephrological work-up of proximal tubular function showed decreased fractional phosphate and percent aminoacid reabsorption in 37.1 and 56.7% of cases, respectively, and the excretion of alpha 1-microglobulin and N-acetyl-beta-D-glucosaminidase was elevated in 44.4 and 23.5%. Glomerular function was well preserved in the majority of patients. Tubular dysfunction was confirmed by silver-stained SDS PAGE of urine which showed mostly low molecular weight proteinuria. CPL has been shown to result in renal magnesium loss and reduced glomerular filtration rate, and its toxicity clearly differs from IFO-mediated tubulopathy. Our data suggest that subclinical impairment of proximal tubular function was significantly increased by additional CPL therapy. We conclude that CPL may enhance IFO-mediated nephrotoxicity and that a substantial number of patients is at risk of developing persistent tubular dysfunction leading to metabolic bone disease.