Acute and long-term nephrotoxicity of cis-platinum in man

To detect whether the nephrotoxicity of cis-diamminedichloroplatinum (DDP) is acute and can be demonstrated at an early stage in man, a method for estimating the function of the kidneys during intensive hydration was devised. The method includes a calculation of the clearance of 125I-orthoiodohippurate and an estimation of the glomerular filtration rate (GFR) from fast changes of the extracellular volume (ECV) and the mean transit time of 99mTc-DTPA in this volume. We examined nine patients with testicular cancer on 2 consecutive days for acute nephrotoxicity while they were undergoing treatment with cis-platinum. Placebo was given on day 1, cis-platinum on day 2. On both days the patients were hydrated with 4 l saline, glucose, and mannitol (0.51) over a period of 4 h, which resulted in an increase of 125I-orthoiodohippurate clearance on both days (P less than 0.01). The increase was, however, lower on the day of treatment with cis-platinum than on the day with placebo (P less than 0.05). There were no acute changes in the GFR. This indicates that treatment with DDP inhibits the active transport of 125I-orthoiodohippurate in the tubules; that is to say there is an acute effect on the kidney function. There were no acute changes in the GFR, but in the long-term followup study we found that the GFR had decreased significantly (P less than 0.05) after 2 months of treatment. During the first year after the initiation of treatment the GFR changes were found to progress. A significant increase in se-creatinine was not observed until 6 months after the initiation of treatment (P less than 0.05). The degree of chronic nephrotoxicity did not correlate in individual patients with the acute changes in kidney function.