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Accumulation of advanced glycation end products and beta 2-microglobulin in fibrotic thickening of the peritoneum in long-term peritoneal dialysis patients

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  • Artificial Kidney / Dialysis
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Abstract

Characteristics of pathological alterations in long-term peritoneal dialysis (PD) are thickening of submesothelial compact (SMC) zone, small-vessel vasculopathy, and loss of mesothelial cells. Bioincompatible PD fluid plays crucial roles in peritoneal injury. Encapsulating peritoneal sclerosis (EPS), a rare and serious complication, occurred in patients on long-term PD or frequent peritonitis episodes, and ~50 % of EPS developed after PD cessation. We hypothesized that PD-related peritoneal injury factors induced by bioincompatible PD fluid accumulated in the peritoneum and might induce EPS. We therefore examined the accumulation of advanced glycation end products (AGE) and beta 2-microglobulin (β2M) in peritoneum and evaluated the relationship between their accumulation, clinical parameters, and outcome after PD cessation. Forty-five parietal peritoneal specimens were obtained from 28 PD patients, 14 uremic patients, and three patients with normal kidney function. The peritoneal equilibration test was used for peritoneal function. AGE- and β2M-expressing areas were found in vascular walls, perivascular areas, and the deep layer of the SMC in short-term PD patients and extended over the entire SMC in long-term patients. Peritonitis and prolonged PD treatment aggravated peritoneal thickening and the proportion of AGE-expressing areas. The proportion of β2M-expressing areas was increased in long-term PD patients. Thickening of the SMC and the proportions of AGE- and β2M-expressing areas were not related to ascites or EPS after PD withdrawal. It appears that the increased proportion of AGE and β2M deposition induced by long-term exposure of PD fluid may be a marker of peritoneal injury.

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References

  1. Di Paolo N, Sacchi G, De Mia M, et al. Morphology of the peritoneal membrane during continuous ambulatory peritoneal dialysis. Nephron. 1986;44:204–11.

    Article  PubMed  Google Scholar 

  2. Gotloib L, Shostak A. Ultrastructural morphology of the peritoneum: new findings and speculations on transfer of solutes and water during peritoneal dialysis. Perit Dial Bull. 1987;7:119–29.

    Google Scholar 

  3. Honda K, Nitta K, Horita S, Yumura W, Nihei H. Morphological changes in the peritoneal vasculature of patients on CAPD with ultrafiltration failure. Nephron. 1996;72:171–6.

    Article  CAS  PubMed  Google Scholar 

  4. Williams JD, Craig KJ, Topley N, et al. Peritoneal Biopsy Study Group: morphologic changes in the peritoneal membrane of patients with renal disease. J Am Soc Nephrol. 2002;13:470–9.

    PubMed  Google Scholar 

  5. Kawanishi H, Kawaguchi Y, Fukui H, et al. Encapsulating peritoneal sclerosis in Japan: a prospective, controlled, multicenter study. Am J Kidney Dis. 2004;44:729–37.

    Article  PubMed  Google Scholar 

  6. Honda K, Oda H. Pathology of encapsulating peritoneal sclerosis. Perit Dial Int. 2005;25:S19–29.

    PubMed  Google Scholar 

  7. Nakayama M, Kawaguchi Y, Yamada K, et al. Immunohistochemical detection of advanced glycosylation end-products in the peritoneum and its possible pathophysiological role in CAPD. Kidney Int. 1997;51:182–6.

    Article  CAS  PubMed  Google Scholar 

  8. Ohashi K. Pathogenesis of beta2-microglobulin amyloidosis. Pathol Int. 2001;51:1–10.

    Article  CAS  PubMed  Google Scholar 

  9. Ohashi K, Hara M, Kawai R, et al. Cervical discs are most susceptible to beta2-microglobulin amyloid deposition in the vertebral column. Kidney Int. 1992;41:1646–52.

    Article  CAS  PubMed  Google Scholar 

  10. Argiles A, Mourad G, Kerr PG, et al. Cells surrounding haemodialysis-associated amyloid deposits are mainly macrophages. Nephrol Dial Transplant. 1994;9:662–7.

    CAS  PubMed  Google Scholar 

  11. Yokoyama K, Yoshida H, Matsuo N, et al. Serum beta2 microglobulin (beta2MG) level is a potential predictor for encapsulating peritoneal sclerosis (EPS) in peritoneal dialysis patients. Clin Nephrol. 2008;69:121–6.

    Article  CAS  PubMed  Google Scholar 

  12. Eichner T, Radford SE. Understanding the complex mechanisms of β2-microglobulin amyloid assembly. FEBS J. 2011;278:3868–83.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Osada S, Hamada C, Shimaoka T, et al. Alterations in proteoglycan components and histopathology of the peritoneum in uraemic and peritoneal dialysis (PD) patients. Nephrol Dial Transplant. 2009;24:3504–12.

    Article  CAS  PubMed  Google Scholar 

  14. Yamaguchi I, Suda H, Tsuzuike N, et al. Glycosaminoglycan and proteoglycan inhibit the depolymerization of beta2-microglobulin amyloid fibrils in vitro. Kidney Int. 2003;64:1080–8.

    Article  CAS  PubMed  Google Scholar 

  15. Lo WK, Kawanishi H. Encapsulating peritoneal sclerosis–medical and surgical treatment. Perit Dial Int. 2009;29 Suppl 2:S211–4.

    PubMed  Google Scholar 

  16. Twardowski ZJ, Nolph kDa, Khanna R, et al. Peritoneal equilibration test. Perit Dial Bull. 1987;7:138–47.

    Google Scholar 

  17. Ikeda K, Higashi T, Sano H, et al. N(epsilon)-(carboxymethyl) lysine protein adduct is a major immunological epitope in proteins modified with advanced glycation end products of the Maillard reaction. Biochemistry. 1996;35:8075–83.

    Article  CAS  PubMed  Google Scholar 

  18. Solé M, Muñoz-Gómez J, Campistol JM. Role of amyloid in dialysis-related arthropathies. A morphological analysis of 23 cases. Virchows Arch A Pathol Anat Histopathol. 1990;417:523–8.

    Article  PubMed  Google Scholar 

  19. Shimaoka T, Hamada C, Kaneko K, et al. Quantitative evaluation and assessment of peritoneal morphologic changes in peritoneal dialysis patients. Nephrol Dial Transplant. 2010;10:3379–85.

    Article  Google Scholar 

  20. Nakamura S, Miyazaki S, Sasaki S, et al. Localization of imidazolone in the peritoneum of CAPD patients: a factor for a loss of ultrafiltration. Am J Kidney Dis. 2001;38:S107–10.

    Article  CAS  PubMed  Google Scholar 

  21. Miyata T, Horie K, Ueda Y, et al. Advanced glycation and lipid oxidation of the peritoneal membrane: respective roles of serum and peritoneal fluid reactive carbonyl compounds. Kidney Int. 2000;58:425–35.

    Article  CAS  PubMed  Google Scholar 

  22. Honda K, Hamada C, Nakayama M, Peritoneal Biopsy Study Group of the Japanese Society for Peritoneal Dialysis, et al. Impact of uremia, diabetes, and peritoneal dialysis itself on the pathogenesis of peritoneal sclerosis: a quantitative study of peritoneal membrane morphology. Clin J Am Soc Nephrol. 2008;3:720–8.

    Article  PubMed Central  PubMed  Google Scholar 

  23. Park MS, Lee HA, Chu WS, et al. Peritoneal accumulation of AGE and peritoneal membrane permeability. Perit Dial Int. 2000;20:452–60.

    CAS  PubMed  Google Scholar 

  24. Brownlee M, Vlassara H, Cerami M. Nonenzymatic glycosylation and the pathogenesis of diabetic complications. Ann Intern Med. 1984;101:527–37.

    Article  CAS  PubMed  Google Scholar 

  25. Bucciarelli LG, Ananthakrishnan R, Hwang YC, et al. RAGE and modulation of ischemic injury in the diabetic myocardium. Diabetes. 2008;57:1941–51.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. De Vriese AS, Tilton RG, Mortier S, Lameire NH. Myofibroblast transdifferentiation of mesothelial cells is mediated by RAGE and contributes to peritoneal fibrosis in uraemia. Nephrol Dial Transplant. 2006;21:2549–55.

    Article  PubMed  Google Scholar 

  27. Lai KN, Lai KB, Lam CW, et al. Changes of cytokine profiles during peritonitis in patients on continuous ambulatory peritoneal dialysis. Am J Kidney Dis. 2000;35:644–52.

    Article  CAS  PubMed  Google Scholar 

  28. Naiki H, Yamamoto S, Hasegawa K, et al. Molecular interactions in the formation and deposition of beta2-microglobulin-related amyloid fibrils. Amyloid. 2005;12:15–25.

    Article  CAS  PubMed  Google Scholar 

  29. Miyata T, Inagi R, Iida Y, et al. Involvement of beta 2-microglobulin modified with advanced glycation end products in the pathogenesis of hemodialysis-associated amyloidosis. Induction of human monocyte chemotaxis and macrophage secretion of tumor necrosis factor-alpha and interleukin-1. J Clin Invest. 1994;93:521–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Correspondence to Chieko Hamada.

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Deceased: H. Nakamoto.

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Nakamoto, H., Hamada, C., Shimaoka, T. et al. Accumulation of advanced glycation end products and beta 2-microglobulin in fibrotic thickening of the peritoneum in long-term peritoneal dialysis patients. J Artif Organs 17, 60–68 (2014). https://doi.org/10.1007/s10047-013-0741-1

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  • DOI: https://doi.org/10.1007/s10047-013-0741-1

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