Effects of cisplatin on different measures of glomerular function in the human kidney with special emphasis on high-dose.

To investigate the effect of high-dose cisplatin (40 mg/m2 daily for 5 days), 51Cr-EDTA clearance was used as a measure of glomerular filtration rate (GFR). 51Cr-EDTA clearance decreased significantly from 109 +/- 3 ml/min * 1.73 m2 to 68 +/- 3 ml/min * 1.73 m2 after three cycles of cisplatin and remained at this decreased level during the observation period (24 months). To determine the reliability of creatinine as a measure of GFR, we compared the simultaneous clearance of creatinine to that of 51Cr-EDTA. A good correlation between 51Cr-EDTA clearance and creatinine clearance was observed before and 3 months after termination of treatment, but no correlation was found during treatment. S-creatinine decreased significantly during treatment, probably due to muscle wasting. We conclude that s-creatinine and creatinine clearance are unsuitable measures of glomerular function during high-dose cisplatin treatment. All patients developed proteinuria during treatment. The changes in clearance ratios of beta-2-microglobulin/albumin and IgG/albumin show that the proteinuria observed during cisplatin infusion is predominantly of tubular origin, whereas the proteinuria between the treatment periods is mainly of glomerular origin.