Abstract | BACKGROUND: 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 micromol/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.
|
Authors | Femke Waanders, Else van den Berg, Ryoji Nagai, Ingrid van Veen, Gerjan Navis, Harry van Goor |
Journal | Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
(Nephrol Dial Transplant)
Vol. 23
Issue 2
Pg. 518-24
(Feb 2008)
ISSN: 1460-2385 [Electronic] England |
PMID | 17905804
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Glycation End Products, Advanced
- Pyridoxamine
|
Topics |
- Animals
- Chronic Disease
- Glycation End Products, Advanced
(antagonists & inhibitors)
- Kidney Diseases
(etiology, metabolism, prevention & control)
- Kidney Transplantation
(adverse effects)
- Male
- Pyridoxamine
(therapeutic use)
- Rats
|