The influence of cisplatin and unilateral nephrectomy on the response of the rat kidney to irradiation.
Cisplatin was administered as a single i.p. dose of 5 mg/kg to WAG/Rij rats at intervals of 7 days or 0.5 h before, or 7 days after graded X-ray doses to the left kidney. The right kidney was surgically removed 4 weeks after irradiation. Renal function was determined by measuring total urine volume excreted in 24 h, urine osmolality and serum urea. The severity of alterations in the various anatomic compartments of the kidney induced by the various treatments were graded histologically. The administration of 2 or 5 mg/kg cisplatin alone did not alter any of the kidney function parameters. Isoeffective radiation doses calculated for each of the functional parameters continuously decreased with increasing time after treatment. Differences between the isoeffective doses for the three combined treatments and for treatment with irradiation alone were only observed for urine osmolality and urine volume which primarily are tubular-related functional parameters. The histopathological grading studies also indicated that enhancement by cisplatin of radiation-induced damage was almost entirely confined to the tubules. The results of this study indicate that the sequence and length of time between treatments is an important variable in the development of cisplatin plus radiation-induced renal injury, but that none of the tested combinations showed a more than additive toxicity.
van Rongen
E
E
Radiobiological Institute TNO, Rijswijk, The Netherlands.
van der Kogel
J
J
Durham
S K
SK
D000818:Animals; D002945:Cisplatin / Q000494:pharmacology*; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000502:physiology / Q000528:radiation effects*; D009392:Nephrectomy; D009994:Osmolar Concentration; D051381:Rats; D014508:Urea / Q000097:blood; D014556:Urine
D014508:Urea; D002945:Cisplatin