Influence of Icodextrin on Plasma and Dialysate Levels of N∊-(Carboxymethyl)Lysine and N∊-(Carboxyethyl)Lysine

2005 ◽  
Vol 25 (6) ◽  
pp. 591-595 ◽  
Author(s):  
Constantijn J. Konings ◽  
Casper G. Schalkwijk ◽  
Frank M. van der Sande ◽  
Karel M. Leunissen ◽  
Jeroen P. Kooman

Rationale Standard peritoneal glucose solutions may induce the formation of advanced glycation end products (AGEs). Preliminary data suggest that AGE formation may be less with the use of polyglucose solutions (icodextrin). Therefore, we investigated whether the use of icodextrin for the long dwell would result in a reduction in plasma and dialysate levels of the AGE products N∊-(carboxymethyl) lysine (CML) and N∊-(carboxyethyl)lysine (CEL). Patients and Methods 40 patients were randomized to treatment with standard glucose solutions (1.36%) and icodextrin for the long dwell during a 4-month study period; 32 patients completed the study. CML was assessed by stable isotope dilution/tandem mass spectrometry. Results CML levels in plasma increased significantly in patients treated with icodextrin (0.146 ± 0.056 at start vs 0.188 ± 0.069 μmol/mmol Lys at the end of the study, p < 0.0001) but did not change in the control group (0.183 ± 0.090 vs 0.188 ± 0.085 μmol/mmol Lys). The same held true for CML levels in dialysate (0.28 ± 0.09 at start vs 0.33 ± 0.11 μmol/mmol Lys at the end of the study, p < 0.025). No change was observed in patients treated with the control solutions (0.31 ± 0.11 at start vs 0.31 ± 0.07 μmol/mmol Lys). Conclusion Contrary to the hypothesis, plasma and dialysate levels of CML increased in patients treated using icodextrin for the long dwell.

2004 ◽  
Vol 50 (7) ◽  
pp. 1222-1228 ◽  
Author(s):  
Tom Teerlink ◽  
Rob Barto ◽  
Herman J ten Brink ◽  
Casper G Schalkwijk

Abstract Background: N ε-(Carboxymethyl)lysine (CML) and Nε-(carboxyethyl)lysine (CEL) are two stable, nonenzymatic chemical modifications of protein lysine residues resulting from glycation and oxidation reactions. We developed a tandem mass spectrometric method for their simultaneous measurement in hydrolysates of plasma proteins. Methods: CML and CEL were liberated from plasma proteins by acid hydrolysis after addition of deuterated CML and CEL as internal standards. Chromatographic separation was performed by gradient-elution reversed-phase chromatography with a mobile phase containing 5 mmol/L nonafluoropentanoic acid as ion-pairing agent. Mass transitions of 205.1→84.1 and 219.1→84.1 for CML and CEL, respectively, and 209.1→88.1 and 223.1→88.1 for their respective internal standards were monitored in positive-ion mode. Results: CML and CEL were separated with baseline resolution with a total analysis time of 21 min. The lower limit of quantification was 0.02 μmol/L for both compounds. Mean recoveries from plasma samples to which CML and CEL had been added were 92% for CML and 98% for CEL. Within-day CVs were &lt;7.2% for CML and &lt;8.2% for CEL, and between-day CVs were &lt;8.5% for CML and &lt;9.0% for CEL. In healthy individuals (n = 10), mean (SD) plasma concentrations of CML and CEL were 2.80 (0.40) μmol/L (range, 2.1–3.4 μmol/L) and 0.82 (0.21) μmol/L (range, 0.5–1.2 μmol/L), respectively. In hemodialysis (n = 17) and peritoneal dialysis (n = 9) patients, plasma concentrations of CML and CEL were increased two- to threefold compared with controls, without significant differences between dialysis modes [7.26 (1.36) vs 8.01 (3.80) μmol/L (P = 0.89) for CML, and 1.84 (0.39) vs 1.71 (0.42) μmol/L (P = 0.53) for CEL]. Conclusions: This stable-isotope-dilution tandem mass spectrometry method is suitable for simultaneous analysis of CML and CEL in hydrolysates of plasma proteins. Its robustness makes it suitable for assessing the value of these compounds as biomarkers of oxidative stress resulting from sugar and lipid oxidation.


Sign in / Sign up

Export Citation Format

Share Document