Rm. Rossi et al., ESTIMATION OF IFOSFAMIDE CISPLATINUM-INDUCED RENAL TOXICITY BY URINARY PROTEIN-ANALYSIS, Pediatric nephrology, 8(2), 1994, pp. 151-156
Ifosfamide (IFO) chemotherapy has been reported to result in deToni-De
bre-Fanconi syndrome in a minority of patients only, but evaluation of
tubular transport capacities has identified a substantial number of p
atients as having subclinical tubular dysfunction. After completion of
combination chemotherapy employing IFO (n = 37) or IFO plus cisplatin
um (CPL) (n = 27), glomerular and tubular function was assessed in 64
patients by the urinary excretion of transferrin, IgG, albumin, alpha1
-microglobulin (A1M) and N-acetyl-beta-D-glucosaminidase. Sodium dodec
yl sulphate polyacrylamide gel electrophoresis was performed in 21 pat
ients. The determination of urinary marker proteins was compared with
the glomerular filtration rate, the fractional phosphate and percent a
mino acid reabsorption. A reduced glomerular filtration rate was obser
ved in 9.8% of patients. Tubular dysfunction was frequent, with a pred
ominance of renal amino acid (57%) and A1M (48%) loss. IFO-mediated re
nal toxicity was dose dependent. CPL treatment resulted in significant
enhancement of tubular toxicity induced by IFO, whereas concomitant g
entamicin therapy did not affect tubular function. Measurement of urin
ary protein cannot replace other tests for tubular dysfunction in IFO-
treated patients, because the spectrum of IFO-induced nephrotoxicity i
ncludes 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.