Radiation-induced glomerular thrombus formation and nephropathy are not prevented by the ADP receptor antagonist clopidogrel

Purpose: To assess the effects of kidney irradiation on glomerular adenosin e diphosphatase (ADPase) activity and intraglomerular microthrombus formati on, and their correlation to the development of renal functional impairment . Methods and Materials: C3H/HenAf-nu(+) mice were given single-dose or fract ionated kidney irradiations. Glomerular ase activity was measured using a c erium-based histochemical method. Microthrombus formation within the glomer uli was assessed by a semiquantitative immunohistochemical analysis of fibr inogen/fibrin deposits. Renal function was assessed by the [Cr-51]EDTA rete ntion assay. Results: The ADPase activity was significantly reduced, to approximately 50 % of pretreatment value, 4-40 weeks after 10-16 Gy single-dose irradiation and at 44 weeks after 20 x 2 Gy. No dose-effect relationship was found. An approximately fourfold increase in glomerular fibrinogen/fibrin staining wa s observed at 1 year after irradiation. This increase was not influenced by treating the mice with daily, oral clopidogrel, a platelet ADP receptor an tagonist, which reduced platelet aggregation by more than 75%. Radiation-in duced impairment of glomerular filtration was also not affected by the clop idogrel treatment. Conclusion: These data indicate that irradiation significantly reduced glom erular ADPase activity, which correlated an increased glomerular fibrinogen /fibrin deposition. We were not able to reduce these prothrombotic changes, nor to protect against radiation nephropathy, by pharmacological intervent ion with an ADP-receptor antagonist. (C) 2001 Elsevier Science Inc.