NDT Advance Access published online on April 9, 2007
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfm148
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Reduced systemic advanced glycation endproducts in children receiving peritoneal dialysis with low glucose degradation product content
1University Hospital for Pediatric & Adolescent Medicine, University of Heidelberg, Germany, 2Children's Hospital, University of Vienna, Austria, 3Children's Hospital, University of Essen, Germany, 4Hopital de Hautepierre, University of Strasbourg, France, 5Children's Hospital, University of Jena and 6Charité Children's Hospital, Humboldt University, Berlin, Germany
Correspondence and offprint requests to: Claus Peter Schmitt, MD, Division of Pediatric Nephrology, University Hospital for Pediatric and Adolescent Medicine, Im Neuenheimer Feld 153, 69120 Heidelberg, Germany. Email: claus.peter.schmitt{at}med.uni-heidelberg.de
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Abstract |
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Background. Glucose degradation products (GDP) in peritoneal dialysis (PD) solutions are toxic to the peritoneal membrane and promote the formation of advanced glycation end products (AGE), which contribute to accelerated atherosclerosis and amyloidosis. Double chamber PD solutions have a markedly reduced GDP content.
Methods. We analysed GDP and AGE kinetics in 21 children (7 months to 18 years) on automated PD in a prospective multicentre trial with randomized administration of single chamber, high-GDP and double-chamber, low-GDP dialysis solution for 12 weeks each. Total AGE fluorescence, carboxymethyllysine (CML, ELISA) and 3-deoxyglucosone (3-DG, HPLC) were measured in plasma and PD effluent during a 4 h peritoneal equilibration test. Plasma AGE profiles were assessed by size selective gel permeation chromatography and compared with 23 healthy controls.
Results. Initial effluent 3-DG concentrations were 140 ± 55 and 25 ± 4 µmol/l with high- and low-GDP PD fluid, respectively and declined to 53 ± 32 and 7 ± 2 µmol/l within 4 h dwell time (P < 0.001). The ex vivo AGE generating capacity was three times higher with the high-GDP solution and decreased significantly with dwell time. Plasma AGE levels were 1.8–7.4-fold above those of healthy controls; the elevation was most marked for the small molecular fraction (<2 kDa). Plasma AGE and CML levels were significantly higher after 12 weeks exposure to high-GDP solution (20991 ± 4145 AU and 1505 ± 617 ng/ml) than following treatment with low-GDP fluid (17518 ± 4676 AU and 1151 ± 438 ng/ml; both P < 0.05). Four hour AGE clearance was higher with low-GDP solution (0.74 ± 0.3 vs 0.44 ± 0.15 ml/min*1.73 m2, P < 0.01).
Conclusion. GDP are rapidly absorbed from the peritoneal cavity. Administration of PD solutions with low-GDP content reduces plasma AGE levels and may thus improve the cardiovascular risk profile of dialysed children.
Keywords: advanced glycation endproducts; biocompatibility; children; glucose degradation products; peritoneal dialysis
Received for publication: 12. 1.07
Accepted in revised form: 26. 2.07
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