Reduced systemic advanced glycation end products in children receiving peritoneal dialysis with low glucose degradation product content.
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 micromol/l with high- and low-GDP PD fluid, respectively and declined to 53+/-32 and 7+/-2 micromol/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).


CONCLUSIONS
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.
Schmitt
Claus Peter
CP
Division of Pediatric Nephrology, University Hospital for Pediatric and Adolescent Medicine, University of Heidelberg, Germany. claus.peter.schmitt@med.uni-heidelberg.de
von Heyl
Dorothee
D
Rieger
Susanne
S
Arbeiter
Klaus
K
Bonzel
Klaus Eugen
KE
Fischbach
Michel
M
Misselwitz
Joachim
J
Pieper
Ann-Kathrin
AK
Schaefer
Franz
F
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D018592:Cross-Over Studies; D003847:Deoxyglucose / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D015314:Dialysis Solutions / Q000737:chemistry* / Q000627:therapeutic use; D017127:Glycation End Products, Advanced / Q000096:biosynthesis / Q000097:blood* / Q000737:chemistry; D006801:Humans; D007223:Infant; D008239:Lysine / Q000031:analogs & derivatives / Q000097:blood; D008970:Molecular Weight; D009994:Osmolar Concentration; D010529:Peritoneal Cavity; D010530:Peritoneal Dialysis; D013997:Time Factors
D015314:Dialysis Solutions; D017127:Glycation End Products, Advanced; C060458:3-deoxyglucose; C048496:N(6)-carboxymethyllysine; D003847:Deoxyglucose; D008239:Lysine