The response of the pig kidney to the combined effects of cisplatin and unilateral renal irradiation

Abstract

Seven mature Large White female pigs, approximately 10 months of age received a single dose of cis-dichlorodiammineplatinum(II), c-DDP (2.5 mg/kg body weight). Prior to, and 4 weeks after c-DDP administration, individual kidney glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by [ 99mTc]DTPA and [ 131I]hippuran renography. Of the 5 pigs surviving the c-DDP treatment most exhibited a reduction in both GFR and ERPF; the mean reduction in GFR (36.2 ± 18.9%) was more pronounced than that for ERPF (12.6 ± 19.4%). However, the difference in the severity of the impairment in these two parameters was not significant ( p > 0.55). Haematocrit, haemoglobin and red blood cell counts were markedly reduced 14 days after c-DDP infusion, and despite some recovery evident 21 days after treatment, all three haematological parameters were still reduced 28 days after c-DDP administration. The right kidneys of these 5 animals, plus 5 pigs which did not receive c-DDP, were irradiated with a single dose of 11.9 Gy of 60Co γ-rays. Individual kidney GFR and ERPF was routinely measured up to 24 weeks after irradiation. Pigs in which only the right kidney was irradiated showed a marked increase in both GFR and ERPF values 2 weeks after irradiation. This was followed by a decline in function with a reduction of 50% in terms of ERPF 16 weeks after irradiation. Values then showed some evidence of a recovery in function. There was a concomitant compensatory response by the contralateral unirradiated kidney. Animals that received c-DDP prior to irradiation failed to exhibit the hyperaemic response 2 weeks after irradiation. Moreover, the degree of reduction in renal function was greater than that observed in the irradiated kidneys of pigs receiving radiation alone. Prior treatment with c-DDP did not prevent a compensatory hypertrophie response by the contralateral unirradiated kidney; indeed the GFR in the unirradiated kidneys of c-DDP treated pigs increased at a greater rate than in those pigs which did not receive c-DDP. Thus prior treatment with c-DDP enhances the radiation-induced reduction in individual kidney GFR and ERPF.