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Published on: July 19, 2018
Reduced systemic advanced glycation end products in children receiving peritoneal dialysis with low glucose
Claus Peter Schmitt1, Dorothee von Heyl, Susanne Rieger
1Division of Pediatric Nephrology, University Hospital for Pediatric and Adolescent Medicine, University of Heidelberg, Germany. claus.peter.schmitt@med.uni-heidelberg.de
Insights
Using low-glucose degradation product (GDP) peritoneal dialysis (PD) solutions in children significantly reduced advanced glycation end products (AGEs) and may improve cardiovascular health.
Area of Science:
- Nephrology
- Pediatrics
- Biochemistry
Background:
- Glucose degradation products (GDP) in peritoneal dialysis (PD) solutions are toxic, increasing advanced glycation end products (AGEs) linked to atherosclerosis and amyloidosis.
- Double-chamber PD solutions offer significantly lower GDP content.
Purpose of the Study:
- To evaluate the impact of high-GDP versus low-GDP PD solutions on GDP and AGE kinetics in children undergoing automated PD.
- To assess the effect of PD solutions on plasma AGE profiles and compare them to healthy controls.
Main Methods:
- A prospective multicentre trial randomized 21 children to 12 weeks of high-GDP and low-GDP PD solutions.
- Analyzed GDP (3-deoxyglucosone) and AGE (total fluorescence, CML) in plasma and PD effluent during a 4-hour peritoneal equilibration test.
- Assessed plasma AGE profiles using size exclusion chromatography.
Main Results:
- Low-GDP solutions showed significantly lower initial effluent 3-DG concentrations (25 vs. 140 µmol/l) and reduced ex vivo AGE-generating capacity.
- Children on high-GDP solutions had significantly higher plasma AGE and CML levels after 12 weeks compared to low-GDP solutions.
- Four-hour AGE clearance was significantly higher with low-GDP solutions.
Conclusions:
- GDP are rapidly absorbed from the peritoneal cavity.
- Low-GDP PD solutions effectively reduce plasma AGE levels in children.
- Utilizing low-GDP PD solutions may improve the cardiovascular risk profile in pediatric patients on dialysis.
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).
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.
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