Interaction of cis-diamminedichloroplatinum and renal irradiationon renal function in the young and adult rat

Abstract

The interaction between single low doses of cis-diamminedichloroplatinum(II) (c-DDP) and renal irradiation (7.5, 10, 12.5 Gy) on renal function and systolic blood pressure (SBP) was investigated in young (3-4 weeks old, BW 45-65 g) and adult rats (over 12 weeks old, BW 230-290 g). The glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), plasma creatinine, urea and SBP were measured over 24 weeks. Changes in ERPF, plasma creatinine and urea concentrations paralleled GFR changes, but tended to be less pronounced. In young rats, BW and GFR were 10-20% below control values after c-DDP administration (5 mg/kg BW). Irradiation caused a dose-dependent drop in GFR, starting 4 weeks after irradiation in young rats. When c-DDP was given immediately after irradiation to the young rats, the loss of renal function was more pronounced than after either treatment modality alone. Dose-effect curves for a greater than 25% reduction of the GFR relative to controls (ml/min) after 24 weeks gave an ED50 of 9.8 Gy for irradiation alone and 4.6 Gy for irradiation followed by c-DDP. After correction for the drug effect, dose-effect curves were similar for renal irradiation given alone or followed by c-DDP administration in young rats. In adult rats, c-DDP (2.5 mg/kg BW) or irradiation alone did not significantly alter renal function during the follow-up period. Only 12.5 Gy in combination with c-DDP, caused a significant reduction in GFR after 16 weeks in adult rats. In adult rats data were too limited for probit analysis.(ABSTRACT TRUNCATED AT 250 WORDS)