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NDT Advance Access originally published online on September 28, 2007
Nephrology Dialysis Transplantation 2008 23(2):518-524; doi:10.1093/ndt/gfm589
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© The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org


Renoprotective effects of the AGE-inhibitor pyridoxamine in experimental chronic allograft nephropathy in rats

Femke Waanders1,2, Else van den Berg1,2, Ryoji Nagai3, Ingrid van Veen2, Gerjan Navis1 and Harry van Goor2

1Department of Nephrology, 2Department of Pathology and Laboratory Medicine, University Medical Centre Groningen, The Netherlands and 3Department of Biochemistry, Kumamoto University, School of Medicine, Kumamoto, Japan

Correspondence to: F. Waanders, MD, University Medical Centre Groningen, Department of Nephrology, Room 40.4.45, P.O. Box 30.001, 9700 RB Groningen, The Netherlands. Email: F.Waanders{at}int.umcg.nl



  Abstract

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 controls. Proteinuria, renal function and renal histology of untreated transplanted rats (F–L n = 8, F–F n = 8) were compared to rats receiving PM 2 g/l in drinking water for 20 weeks starting at transplantation (F–L n = 5, F–F n = 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 ± 18 vs 29 ± 3 mg/day), serum creatinine (130 ± 12 vs 98 ± 5 µmol/l), focal glomerulosclerosis (116 ± 27 vs 16 ± 5 AU), glomerular macrophage influx (5.6 ± 0.6 vs 3.3 ± 1.0), interstitial fibrosis (132 ± 24 vs 76 ± 2 AU) and interstitial macrophage influx (47.0 ± 8.7 vs 15.4 ± 5.0. Moreover, PM significantly ameliorated tubular accumulation of pentosidine, compared to untreated allografts (2.5 ± 0.6 vs 0.3 ± 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.

Keywords: advanced glycation end products; chronic allograft nephropathy; kidney transplantation; Maillard reaction; pentosidine; pyridoxamine

Received for publication: 2. 2.07
Accepted in revised form: 2. 8.07


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