NDT Advance Access originally published online on March 15, 2007
Nephrology Dialysis Transplantation 2007 22(7):2097-2098; doi:10.1093/ndt/gfl831
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-Oxoaldehydes in haemodialysis solution
Email: nkeisuke{at}ac.cyberhome.ne.jpSir,
In patients on chronic dialysis treatment, factors that enhance oxidative stress include the uraemic milieu, bio-incompatibility of the dialysis apparatus, and loss of anti-oxidants through dialysis. Furthermore, in peritoneal dialysis (PD) treatment, the PD solution per se has oxidative capacity due to the presence of glucose-derived 
-oxoaldehydes, such as methylglyoxal (MG) and glyoxal (GO). Indeed, recent reports indicate that, in PD patients, -oxoaldehydes play a crucial role in local peritoneal damage [1] and in overall survival [2]. In this context, it is of clinical importance to know whether haemodialysis (HD) solutions contain these molecules. However, clinical data are lacking.
We, therefore, measured MG and GO levels in the commercially available brands of liquid and powder type undiluted HD solutions in Japan; 10 liquid brands from three manufacturers and seven powder brands from two manufacturers. Pure glucose (Wako Chem, Co. Tokyo, Japan) was diluted in ultra-pure water as the control. All of the samples’ glucose levels were adjusted to 3.5%.
In this study, we developed a methodology to measure MG and GO levels, based on previously reported methods [3–7]. Briefly, we assayed MG and GO by derivatization with o-phenylenediamine (o-PD) and electrospray ionization – liquid chromatography – mass spectrometry (ESI/LC/MS) of the resulting quinoxalines, as described by Randell et al. [7], with some modifications. Subsequently, 0.1 ml of 5 M perchloric acid was added to 0.5 ml of samples to create an acidic environment, followed by the addition of 1 nmol of 2,3-dimethylquinoxaline as internal standard (IS) and 10 µmol of o-PD; the samples were incubated at 4°C overnight. The samples were then applied down a prepared C18 SPE column, rinsed with 0.05% formic acid, and the retentate was eluted in 0.3 ml of methanol. They were then filtered through 0.2-µm filters into sample vials. The derivatized dicarbonyl compounds were analysed by high-performance liquid chromatography and ESI/MS, using a time-of-flight mass spectrometer (AccuTOF JMS-T100LC, JEOL Ltd, Tokyo, Japan). The derivatives were resolved by reverse-phase chromatography on a C18 column. The mobile phase consisted of 0.05% formic acid and acetonitrile with a gradient of acetonitrile, at flow rates of 0.2 ml/min at 35°C. Quantification of MG and GO was done by calculating the peak area ratio for each dicarbonyl-derived protonated molecular ion peak intensity (MG; m/z 145, GO; m/z 131) to a protonated molecular internal standard ion peak intensity (2,3-dimethylquinoxaline; m/z 159) in the selected ion monitoring mode.
Both MG and GO were detected in all samples (Figure 1). The levels in the liquid type of HD solutions were not uniform; some brands contained higher GO and MG levels than the control. In the powder types of HD solution, the MG and GO levels were not higher than in the liquid types and control. The GO levels in the liquid type solutions were equivalent to those reported for the new neutralized PD solution, while the MG levels were lower [8]. The final levels of these molecules in the HD solution used clinically decreases further, due to their dilution with water. Nevertheless, since the HD solution is directly shifted to the blood side, these molecules may have a clinical impact.
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It is striking that the MG and GO levels were lower in the powder types of HD solution than in the liquid types. This could be attributed to the glucose powder manufacturing process in powder types, which does not involve heat sterilization. The different findings in these two types of solutions may have clinical importance.
Conflict of interest statement. None declared.
1Tohoku University Graduate
School of Medicine
Research Division of
Dialysis and Chronic Kidney Disease
2Tohoku University Hospital
Department of Blood Purification
3Tohoku University
New Industry Creation Hatchery Center
Life Particle Interaction Engineering Creation
Sendai, Japan
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