ESTIMATION OF IFOSFAMIDE CISPLATINUM-INDUCED RENAL TOXICITY BY URINARY PROTEIN-ANALYSIS

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.