ABSTRACT
Little is known about the association between the rate of cisplatin administration and the severity of cisplatin-induced renal damage in children. The purpose of this study was to compare severity and reversibility of renal damage in children after continuous and repetitive bolus administration of cisplatin and to correlate these data with pharmacokinetic parameters. Study subjects included six children (ten courses) receiving cisplatin as 1-h bolus infusions on three consecutive days (3x40 mg/m2) and four children (eight courses) receiving 72-h continuous infusions (120 mg/m2). In all courses, signs of glomerular and tubular damage were seen, as evidenced by elevated urinary excretion of alpha1-microglobulin, albumin and N-acetyl-beta-D-glucosaminidase and decreased glomerular filtration rate (GFR). Comparing the two infusion regimens, the 1-h bolus administration of cisplatin was followed by significantly higher peak free platinum concentrations in plasma and urine (P<0.001), resulting in lower nadirs of the GFR (P<0.005). Correlations were found between both peak free platinum concentrations in plasma and urine and maxima of urinary albumin and N-acetyl-beta-D-glucosaminidase excretion. Within 12 months after completion of cisplatin therapy, children in the 1-h bolus group had recovered only partially from subclinical nephrotoxicity, with five out of six showing pathological proteinuria. The results provide clear evidence that long-term ciplatin infusions are less nephrotoxic than repetitive bolus infusions.