It has been demonstrated that advanced glycation endproducts (AGEs) are generated in the peritoneal tissue of continuous ambulatory peritoneal dialysis (CAPD) patients [1], and they are closely related to pathological phenomena, such as enhanced solute transport state, ultrafiltration failure (UFF) and mesothelial damage. Sclerotic degeneration of the peritoneum, known as tanned peritoneum, has been observed in patients undergoing long-term CAPD treatment; however, the exact mechanism of its progression has not been elucidated. In this respect, whether AGE formation and furthermore what kind of AGE is involved in this pathology is a question that has yet to be answered. Among the characteristics for AGEs, cross-linking with proteins is well known. To explain this cross-linking phenomenon, dimer formation by carbonyl compounds has been reported. For these cross-linking substances, glyoxal lysine dimer (GOLD) and methylglyoxal lysine dimer (MOLD) have recently been cited [2]. Therefore, in the present study, representative non-cross-linking AGEs [N-(carboxymethyl)lysine (CML) and N
-(carboxyethyl)lysine (CEL)], as well as cross-linking AGEs (GOLD and MOLD), were evaluated in the peritoneal tissue of four patients undergoing regular dialysis, including one suffering from encapsulating peritoneal sclerosis (EPS).
The clinical characteristics of the four patients were the following: case 1 was a 60-year-old male treated with CAPD for 2 years, CAPD was then discontinued because of abdominal surgery unrelated to PD. Case 2 was a 56-year-old male who was on maintenance haemodialysis (HD) for 6 years. He had never undergone PD. He succumbed to septicaemia caused by a pacemaker wire-related infection. Case 3 was a 57-year-old male on CAPD for 6 years. This treatment was subsequently discontinued due to UFF. Case 4 was a 59-year-old male on CAPD for 12 years. He was switched to HD because of UFF and developed EPS 1 year later. He received a corticosteroid treatment for 6 months, which failed to relieve ileus symptoms. Two years after the development of EPS, surgical enterolysis was performed. Tissue samples were collected from the parietal peritoneum of cases 1, 2 and 3. In case 4, the sclerotic serosa over the terminal ileum (a and b) was collected from a sample resected during surgery. The histological finding in case 4 was a thick sclerosis of the ileal surface with new collagenous layers over the surface and hyper-vascularization.
6 N HCl was added to samples, and they were completely hydrolysed for 24 h at 110°C. Then the product was concentrated by evaporation under reduced pressure to measure AGEs (CML and CEL:GC-MASS measurement, GOLD and MOLD:HPLC method). The results of the analysis for each AGE are shown in Figures 1 and 2. Non-cross-linking AGEs (CML and CEL) and cross-linking AGEs (GOLD and MOLD) could be measured in all cases, showing consistent predominance of CML over CEL and GOLD over MOLD. It was also found that the levels of cross-linking AGEs were much higher than those of non-cross-linking AGEs, especially in case with EPS.
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Regarding the origin of CML, the reaction between protein and GO is one of the chemical processes to form CML and GO is produced after the oxidative cleavage of glucose [4]. It has been reported that whatever the process of formation, whether originating from pentose or hexisose by autoxidation or from Amadori products, production of GO in vitro is predominant over that of than MGO (precursor of CEL) [5]. Accordingly, the predominance of CML and GOLD in the peritoneal issue suggests the possibility of enhanced axis of GO/CML/GOLD formation, probably in an environment in which a high glucose concentration and oxidative stress act as the prime factors, especially in those patients undergoing long-term CAPD (Figure 3).
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Conflict of interest statement. None declared.
Division of Kidney and Hypertension The Jikei University School of Medicine 3-19-18, Nishishimbashi Minato-ku, Tokyo, Japan Baxter Japan International Inc.1 4, Rolcobancho Chiyodaku Tokyo Japan Email: mnakayama{at}jikei.ac.jp
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