Estimation of ifosfamide/cisplatinum-induced renal toxicity by urinary protein analysis.
Ifosfamide (IFO) chemotherapy has been reported to result in deToni-Debré-Fanconi syndrome in a minority of patients only, but evaluation of tubular transport capacities has identified a substantial number of patients as having subclinical tubular dysfunction. After completion of combination chemotherapy employing IFO (n = 37) or IFO plus cisplatinum (CPL) (n = 27), glomerular and tubular function was assessed in 64 patients by the urinary excretion of transferrin, IgG, albumin, alpha 1-microglobulin (A1M) and N-acetyl-beta-D-glucosaminidase. Sodium dodecyl sulphate polyacrylamide gel electrophoresis was performed in 21 patients. The determination of urinary marker proteins was compared with the glomerular filtration rate, the fractional phosphate and percent amino acid reabsorption. A reduced glomerular filtration rate was observed in 9.8% of patients. Tubular dysfunction was frequent, with a predominance of renal amino acid (57%) and A1M (48%) loss. IFO-mediated renal toxicity was dose dependent. CPL treatment resulted in significant enhancement of tubular toxicity induced by IFO, whereas concomitant gentamicin therapy did not affect tubular function. Measurement of urinary protein cannot replace other tests for tubular dysfunction in IFO-treated patients, because the spectrum of IFO-induced nephrotoxicity includes dysfunction of different and independent transport mechanisms of the proximal tubular system. Increased urinary A1M excretion is an important indicator of impaired tubular protein reabsorption.
University Children's Hospital, Münster, Germany.
R M
RM
Rossi
C
C
Kist
U
U
Wurster
W R
WR
Külpmann
J H
JH
Ehrich
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000009:adverse effects* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004591:Electrophoresis, Polyacrylamide Gel; D005198:Fanconi Syndrome / Q000139:chemically induced* / Q000652:urine*; D005919:Glomerular Filtration Rate; D006801:Humans; D007069:Ifosfamide / Q000009:adverse effects* / Q000627:therapeutic use; D007223:Infant; D007668:Kidney / Q000187:drug effects*; D007677:Kidney Function Tests; D009369:Neoplasms / Q000188:drug therapy; D011507:Proteinuria / Q000652:urine*
D002945:Cisplatin; D007069:Ifosfamide