[Ifosfamide-induced nephrotoxicity].
BACKGROUND
A number of acquired De-Toni-Debre-Fanconi-Syndromes have been reported after cytostatic treatment with Ifosfamide. For the majority of these patients prognosis of renal function was poor. In our study we evaluated the frequency of subclinical tubulopathies, the influence of the cumulative Ifosfamide dose and other risk factors and the prognosis of once established tubular dysfunction.


METHODS
79 patients after polychemotherapy regimens employing Ifosfamide (n = 39), Ifosfamide plus Cisplatinum (n = 35) or Cisplatinum (n = 5) were examined at least 3 months after completion of therapy. Beside the creatinine-clearance we evaluated glomerular and tubular function by measurement of transferrin, immunoglobuline G, Alpha-1-microglobuline and N-Acetyl-beta-D-Glucosamidaseexcretion and by tubular reabsorption of phosphate and aminoacids.


RESULTS
Renal hyperaminoaciduria was found most often, and there was no linear correlation between the cumulative Ifosfamide-dose and phosphate reabsorption. A reduced glomerular filtration rate and glomerular proteinuria were found in about 10.5% of patients. Approximately half of the patients had tubular dysfunction. Impairment of phosphate reabsorption once established did not normalize in the majority of patients. Cisplatinum was found to worsen the Ifosfamide-induced tubulopathy.


CONCLUSIONS
Our results indicate subclinical tubulopathy after Ifosfamide in a high proportion of patients. This Ifosfamide induced nephrotoxicity is worsened by Cisplatinum and seems to be irreversible for the majority of patients. To describe and to prevent Ifosfamide-induced nephrotoxicity, further studies should focus on: 1. the identification of the risk-groups/patients and additional risk factors, 2. the estimation of the prognosis of once established renal damage, 3. the clarification of the pathomechanism.
Rossi
R
R
Allgemeine Pädiatrie, Universitäts-Kinderklinik Münster.
Rath
B
B
Ullrich
K
K
Ehrich
J H
JH
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D002648:Child; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003404:Creatinine / Q000652:urine; D004305:Dose-Response Relationship, Drug; D005198:Fanconi Syndrome / Q000139:chemically induced* / Q000175:diagnosis; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects*; D007677:Kidney Function Tests; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000601:surgery; D009369:Neoplasms / Q000188:drug therapy*; D009392:Nephrectomy; D011183:Postoperative Complications / Q000139:chemically induced / Q000175:diagnosis; D011507:Proteinuria / Q000139:chemically induced / Q000175:diagnosis; D012307:Risk Factors; D009396:Wilms Tumor / Q000188:drug therapy / Q000601:surgery
D003404:Creatinine; D002945:Cisplatin; D007069:Ifosfamide