PROTECTION FROM CISPLATIN NEPHROTOXICITY BY A68828, AN ATRIAL-NATRIURETIC-PEPTIDE

The ability of a 13 amino acid analog of atrial natriuretic peptide (A NP), A68828, to prevent development of cisplatin toxicity was evaluate d in a rat model. ANP (1 mu g/kg/min), A68828 (10 mu g/kg/min), A68828 (50 mu g/kg/min), or peptide buffer was given as an intravenous infus ion over 1 h beginning 15 min prior to an infusion of 5 mg/kg cisplati n. Animals receiving cisplatin plus peptide buffer vehicle developed p redictable renal failure, with mean plasma creatinine and blood urea n itrogen concentrations of 1.09 +/- 0.09 mg/dL and 50.13 +/- 5.96 mg/dL , 72 h after treatment ANP and A68828 (10 mu g/kg/min) attenuated the increase in these indices of nephrotoxicity (mean plasma creatinine 0. 86 +/- .06 mg/dL and 0.76 +/- 0.11 mg/dL, respectively). Surprisingly, the higher dose of A68828 (50 mu g/kg/min) did not reduce cisplatin n ephrotoxicity (72-h plasma creatinine 1.61 +/- 0.34 mg/dL). These resu lts indicate that a short-term infusion of ANP or the analog A68828 ca n reduce the severity of cisplatin toxicity. At high doses of A68828 t he beneficial effects of treatment may be lost.