Background. Advanced glycation end products (AGEs) are involved in diabetic nephropathy (DN). The AGE formation inhibitor pyridoxamine (PM) is renoprotective in DN and in normoglycaemic obese Zucker rats. In chronic allograft nephropathy (CAN), renal AGE accumulation occurs as well. Methods. To investigate whether inhibition of AGE formation is renoprotective in CAN, we studied the Fisher 344 to Lewis (F-L) allograft rat model of experimental CAN. Fisher to Fisher (F-F) isografts served as

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... ols. Proteinuria, renal function and renal histology of untreated transplanted rats (F-L n ¼ 8, F-F n ¼ 8) were compared to rats receiving PM 2 g/l in drinking water for 20 weeks starting at transplantation (F-L n ¼ 5, F-F n ¼ 10). All rats received cyclosporin A (1.5 mg/kg/day) for 10 days after transplantation to prevent early acute rejection. Results. Compared to untreated allografts, PM significantly decreased proteinuria (76 AE 18 vs 29 AE 3 mg/ day), serum creatinine (130 AE 12 vs 98 AE 5 mmol/l), focal glomerulosclerosis (116 AE 27 vs 16 AE 5 AU), glomerular macrophage influx (5.6 AE 0.6 vs 3.3 AE 1.0), interstitial fibrosis (132 AE 24 vs 76 AE 2 AU) and interstitial macrophage influx (47.0 AE 8.7 vs 15.4 AE 5.0. Moreover, PM significantly ameliorated tubular accumulation of pentosidine, compared to untreated allografts (2.5 AE 0.6 vs 0.3 AE 0.3, all p < 0.05). In the isograft controls, these values did not differ between untreated and PM treated rats. Conclusion. PM exerts renoprotective effects and decreases renal pentosidine accumulation in experimental CAN, suggesting a detrimental role for renal AGE accumulation in the pathogenesis of renal damage in this non-diabetic model. These results indicate that inhibition of AGE formation might be a useful adjunct therapy to attenuate CAN.