Acute changes in urine protein excretion may predict chronic ifosfamide nephrotoxicity: a preliminary observation.
OBJECTIVE
To evaluate proteinuria occurring early after ifosfamide therapy and to assess the use of changes in proteinuria in the prediction of severe chronic nephrotoxicity.


METHODS
One-dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis was used to characterize urine protein excretion in 12 children with solid tumours before and after the first course of ifosfamide treatment, and in 24 healthy children. Chronic nephrotoxicity was evaluated at 6 months after ifosfamide treatment and graded as none, mild, moderate or severe.


RESULTS
Urine from healthy children and from 10 of 12 patients before ifosfamide therapy showed a protein band with a molecular weight (95.4 kDa) corresponding to that of Tamm-Horsfall protein but no lower molecular weight proteins. After the first course of ifosfamide this 95.4-kDa protein was lost in six of ten patients with a concomitant appearance of a low molecular weight proteinuria (< 70 kDa) in eight. Tamm-Horsfall protein was lost in two of five patients who subsequently developed no or mild nephrotoxicity and in four of five patients who subsequently developed moderate or severe nephrotoxicity.


CONCLUSIONS
Early subclinical changes in urine protein excretion after ifosfamide, manifested by a loss of Tamm-Horsfall protein excretion, may be predictive of subsequent chronic nephrotoxicity.
MacLean
F R
FR
Sir James Spence Institute of Child Health, University of Newcastle Upon Tyne, Royal Victoria Infirmary, UK.
Skinner
R
R
Hall
A G
AG
English
M
M
Pearson
A D
AD
D000293:Adolescent; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000009:adverse effects* / Q000627:therapeutic use; D007223:Infant; D007668:Kidney / Q000187:drug effects*; D008297:Male; D009088:Mucoproteins / Q000187:drug effects* / Q000652:urine; D009369:Neoplasms / Q000188:drug therapy / Q000652:urine*; D011507:Proteinuria / Q000139:chemically induced*; D058949:Uromodulin
D018906:Antineoplastic Agents, Alkylating; D009088:Mucoproteins; C548612:UMOD protein, human; D058949:Uromodulin; D007069:Ifosfamide