What a waste.

The nephrotoxic activity of cis-diammine-dichloroplatinum (CDDP), an important cytostatic agent in modern cancer chemotherapy, has most commonly limited the effective use of this drug (Rozencweig et al., 1977; Gonzalez-Vitale et al., 1977; Campbell et al., 1983; Offerman et al., 1984). As in man, typical pathological changes in the kidneys after CDDP application can also be found in laboratory animals (Kociba & Sleight, 1971; Choie et al., 1981; Goldstein & Gilbert, 1983). These renal lesions are dose and time dependant, and mainly localized in the outer stripe of the medulla. By pretreatment hydration with 0.9% NaCl and forced diuresis particularly, the toxic activity of CDDP on the kidneys of human patients can be partially reduced, but not completely inhibited (Hayes et al., 1977; Ostrow et al., 1981; Ozols et al., 1984). Sodium 2-mercaptoethane-sulfonate (INN: MESNA; Uromitexan' (Asta-Werke AG, FRG, and Boehringer Ingelheim Hospital Division, UK and Eire) is an almost non-toxic thio compound. It is already used in patients who receive oxazaphosphorine cytostatics, such as cyclophosphamide and ifosfamide, to protect the efferent urinary tract, especially the bladder, against the toxic metabolites of these chemotherapeutic agents (Scheef et al., 1979; Brock, 1980). Until now, protection against the nephrotoxicity of CDDP through MESNA has not been established. CDDP, being a heavy-metal complex, might easily be chelated by sulfhydryl containing compounds, eg by the highly reactive thio-compound MESNA. The only known metabolite of MESNA is MESNA disulfide, which is not capable of reaction (Brock et al., 1982). After oral administration of MESNA, this inactive metabolite occurs almost solely in the blood. So it could be anticipated that intravascular DIMESNA would not react with CDDP or with intravenously administered antiemetics, which are absolutely necessary in humans, because of the emetic effects of cis-platin. After i.v. administration of MESNA, the disulfide is also formed spontaneously by autooxidation and found predominantly in the blood stream (Brock et al., 1982). It is eliminated through the kidneys by glomerular filtration, and, to a great extent, reduced to MESNA during excretion. In the tubular lumen MESNA would then be available for reactions, eg with CDDP, which mainly damages the renal tubules. In our investigations we managed to completely prevent renal damage in BD IX rats after a single dose of 3mg CDDPkg-t body weight i.p. (half of LD50 in this strain) by additional per os administration of MESNA. This protection showed