Cisplatin nephrotoxicity in children after continuous 72-h and 3x1-h infusions

Little is known about the association between the rate of cisplatin adminis tration and the severity of cisplatin-induced renal damage in children. The purpose of this study was to compare severity and reversibility of renal d amage in children after continuous and repetitive bolus administration of c isplatin and to correlate these data with pharmacokinetic parameters. Study subjects included six children (ten courses) receiving cisplatin as 1-h bo lus infusions on three consecutive days (3x40 mg/m(2)) and four children (e ight courses) receiving 72-h continuous infusions (120 mg/m(2)). In all cou rses, signs of glomerular and tubular damage were seen,as evidenced by elev ated urinary excretion of alpha (1)-microglobulin, albumin and N-acetyl-bet a -D-glucosa-minidase and decreased glomerular filtration rate (GFR). Compa ring the two infusion regimens, the 1-h bolus administration of cisplatin w as followed by significantly higher peak free platinum concentrations in pl asma 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-glucos aminidase excretion. Within 12 months after completion of cisplatin therapy , children in the 1-h bolus group had recovered only partially from subclin ical nephrotoxicity, with five out of six showing pathological proteinuria. The results provide clear evidence that long-term ciplatin infusions are l ess nephrotoxic than repetitive bolus infusions.