Amyloidosis, Beta2M (Dialysis-Related) 

  • Author: Anita Basu, MD; Chief Editor: Vecihi Batuman, MD, FACP, FASN   more...
 
Updated: Jun 3, 2010
 

Background

Beta-2-microglobulin amyloidosis is a disabling condition that affects patients undergoing long-term hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD).[1, 2] Case reports involving patients with near end-stage renal disease also exist. It does not affect individuals with normal or mildly reduced renal function or patients with a functioning renal transplant.

Beta-2-microglobulin is a major constituent of amyloid fibrils.[3] Its accumulation has been shown to invade synovial membranes and osteoarticular sites, causing destructive osteoarthropathies, such as carpal tunnel syndrome, flexor tenosynovitis, subchondral bone cysts, and erosions, as well as pathologic fractures.

Visceral involvement has been found in different organs, such as the gastrointestinal tract, heart, and tongue, but overt manifestations are rare.

Next

Pathophysiology

Beta-2-microglobulin is a glycosylated polypeptide with a molecular weight of 11,800 dalton. It comprises the beta chain of the human leukocyte antigen (HLA) class I molecule and has a prominent beta-pleated structure with characteristic amyloid fibrils. Beta-2-microglobulin is present on the surface of most nucleated cells and in most biologic fluids, including urine and synovial fluid. It circulates as an unbound monomer distributed in the extracellular space and polymerizes to form amyloid deposits in a variety of tissues. Two or three conformational isomers of beta(2)m are recognized in human serum by capillary electrophoresis.[4]

In the normally functioning kidney, beta-2-microglobulin is cleared by glomerular filtration and is catabolized in the proximal tubules. Reference range serum levels are 1.5-3 mg/L. In renal failure, impaired renal catabolism causes an increase in synthesis and a release of beta-2-microglobulin, and levels can increase 10- to 60-fold. Retention and accumulation of this type of amyloid protein is presumed to be the main pathogenic process underlying beta-2-microglobulin amyloidosis. There is also some suggestion that the dialysis process itself may stimulate beta-2-microglobulin synthesis by activation of complements and cytokine production. However, it is unlikely that this is a significant mechanism of dialysis-related amyloidosis (DRA) since the disease is also seen in patients on CAPD and people who have never been on dialysis.

Previous
Next

Epidemiology

Frequency

United States

The incidence of DRA in the United States is not known; however, past studies have suggested an incidence of greater than 95% in patients on dialysis for more than 15 years.

Some European studies have suggested that DRA can be seen in as many as 20% of patients after 2-4 years of HD and in 100% after 13 years of HD. However, again, the overall incidence and prevalence of beta-2-microglobulin amyloidosis are not clear.

Most studies have focused on HD-associated amyloidosis and have been done before high-flux dialyzer use became commonplace.

There is some mention in the literature that the incidence and the prevalence in CAPD are less than in HD (because of residual renal function), while other European studies suggest that there is no significant difference in both the incidence and the prevalence.

Beta-2-microglobulin amyloidosis evolves predictably over time and is rare in the first few years of HD.

International

Studies in Japan suggest that most patients with carpal tunnel syndrome associated with beta-2-microglobulin amyloid deposits have undergone HD for 10 years or more. In one study, up to 50% of patients developed this complication after 20 years, and the percentage was even higher after 25 years.

Mortality/Morbidity

Patients receiving long-term dialysis can experience disabling musculoskeletal complications.[5] For individuals who are able to undergo renal transplantation, progression of the disease can be halted, but regression is unlikely. Rarely, submucosal bowel deposits have resulted in massive GI bleeding. Case reports of severe pulmonary hypertension and heart failure due to beta-2-microglobulin amyloid deposits in the interstitium and/or vasculature of the cardiovascular system also exist.

Race

No data comparing the incidence of disease in different groups exist.

Sex

The sex of the individual does not seem to influence risk.

Age

The incidence correlates with the increased age of the individual and the time on dialysis.

Previous
Proceed to Clinical Presentation
 
 
Contributor Information and Disclosures
Author

Anita Basu, MD  Assistant Professor of Medicine, University of Mississippi School of Medicine; Staff Nephrologist, GV (Sonny) Montgomery Veterans Affairs Medical Center

Anita Basu, MD is a member of the following medical societies: American College of Physicians and National Kidney Foundation

Disclosure: Nothing to disclose.

Coauthor(s)

Carol A Bogdan, MD  Consulting Staff, Coastal Cancer Center, Myrtle Beach, SC

Disclosure: Nothing to disclose.

Reynaldo Matute, MD  Clinical Assistant Professor, Department of Internal Medicine, Division of Nephrology, New York Medical College

Reynaldo Matute, MD is a member of the following medical societies: American Society of Nephrology and National Kidney Foundation

Disclosure: Nothing to disclose.

Specialty Editor Board

Donald A Feinfeld, MD, FACP, FASN  Consulting Staff, Division of Nephrology & Hypertension, Beth Israel Medical Center

Donald A Feinfeld, MD, FACP, FASN is a member of the following medical societies: American Academy of Clinical Toxicology, American Society of Hypertension, American Society of Nephrology, and National Kidney Foundation

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Senior Pharmacy Editor, eMedicine

Disclosure: eMedicine Salary Employment

George R Aronoff, MD  Director, Professor, Departments of Internal Medicine and Pharmacology, Section of Nephrology, Kidney Disease Program, University of Louisville School of Medicine

George R Aronoff, MD is a member of the following medical societies: American Federation for Medical Research, American Society of Nephrology, Kentucky Medical Association, and National Kidney Foundation

Disclosure: Nothing to disclose.

Rebecca J Schmidt, DO, FACP, FASN  Professor of Medicine, Section Chief, Department of Medicine, Section of Nephrology, West Virginia University School of Medicine

Rebecca J Schmidt, DO, FACP, FASN is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Nephrology, International Society of Nephrology, National Kidney Foundation, Renal Physicians Association, and West Virginia State Medical Association

Disclosure: Abbott Grant/research funds Speaking and teaching; AMAG Honoraria Speaking and teaching; Amgen Honoraria Speaking and teaching; Ortho Biotech Honoraria Speaking and teaching; Renal Ventures Ownership interest Other

Chief Editor

Vecihi Batuman, MD, FACP, FASN  Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Medicine Service, Southeast Louisiana Veterans Health Care System

Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, and International Society of Nephrology

Disclosure: Nothing to disclose.

References

  1. Drueke TB. Beta2-microglobulin and amyloidosis. Nephrol Dial Transplant. 2000;15 Suppl 1:17-24. [Medline].

  2. Tan SY, Baillod R, Brown E, Farrington K, Soper C, Percy M, et al. Clinical, radiological and serum amyloid P component scintigraphic features of beta2-microglobulin amyloidosis associated with continuous ambulatory peritoneal dialysis. Nephrol Dial Transplant. Jun 1999;14(6):1467-71. [Medline].

  3. Bely M, Kapp P, Szabo TS, Lakatos T, Apáthy A. Electron microscopic characteristics of beta2-microglobulin amyloid deposits in long-term haemodialysis. Ultrastruct Pathol. Nov-Dec 2005;29(6):483-91. [Medline].

  4. Uji Y, Motomiya Y, Ando Y. A Circulating beta(2)-Microglobulin Intermediate in Hemodialysis Patients. Nephron Clin Pract. Feb 5 2009;111(3):c173-c181. [Medline].

  5. Danesh F, Ho LT. Dialysis-related amyloidosis: history and clinical manifestations. Semin Dial. 2001 Mar-Apr;14(2):80-5. [Medline].

  6. Kelly A, Apostle K, Sanders D, Bailey H. Musculoskeletal pain in dialysis-related amyloidosis. Can J Surg. Aug 2007;50(4):305-6. [Medline].

  7. Yamamoto S, Kazama JJ, Maruyama H, Nishi S, Narita I, Gejyo F. Patients undergoing dialysis therapy for 30 years or more survive with serious osteoarticular disorders. Clin Nephrol. Dec 2008;70(6):496-502. [Medline].

  8. Saito A, Gejyo F. Current clinical aspects of dialysis-related amyloidosis in chronic dialysis patients. Ther Apher Dial. Aug 2006;10(4):316-20. [Medline].

  9. Matsuo K, Nakamoto M, Yasunaga C, Goya T, Sugimachi K. Dialysis-related amyloidosis of the tongue in long-term hemodialysis patients. Kidney Int. Sep 1997;52(3):832-8. [Medline].

  10. Thornalley PJ. Glycation free adduct accumulation in renal disease: the new AGE. Pediatr Nephrol. Nov 2005;20(11):1515-22. [Medline].

  11. Miyata T, Hori O, Zhang J, Yan SD, Ferran L, Iida Y, et al. The receptor for advanced glycation end products (RAGE) is a central mediator of the interaction of AGE-beta2microglobulin with human mononuclear phagocytes via an oxidant-sensitive pathway. Implications for the pathogenesis of dialysis-related amyloidosis. J Clin Invest. Sep 1 1996;98(5):1088-94. [Medline].

  12. Kiss E, Keusch G, Zanetti M, Jung T, Schwarz A, Schocke M, et al. Dialysis-related amyloidosis revisited. AJR Am J Roentgenol. Dec 2005;185(6):1460-7. [Medline].

  13. Lornoy W, Becaus I, Billiouw JM, Sierens L, Van Malderen P, D'Haenens P. On-line haemodiafiltration. Remarkable removal of beta2-microglobulin. Long-term clinical observations. Nephrol Dial Transplant. 2000;15 Suppl 1:49-54. [Medline].

  14. Furuya R, Kumagai H, Takahashi M, Sano K, Hishida A. Ultrapure dialysate reduces plasma levels of beta2-microglobulin and pentosidine in hemodialysis patients. Blood Purif. 2005;23(4):311-6. [Medline].

  15. Davankov V, Pavlova L, Tsyurupa M, Brady J, Balsamo M, Yousha E. Polymeric adsorbent for removing toxic proteins from blood of patients with kidney failure. J Chromatogr B Biomed Sci Appl. Feb 28 2000;739(1):73-80. [Medline].

  16. Kutsuki H. beta(2)-Microglobulin-selective direct hemoperfusion column for the treatment of dialysis-related amyloidosis. Biochim Biophys Acta. Nov 10 2005;1753(1):141-5. [Medline].

  17. Ozawa D, Yagi H, Ban T, Kameda A, Kawakami T, Naiki H, et al. Destruction of amyloid fibrils of a beta2-microglobulin fragment by laser beam irradiation. J Biol Chem. Jan 9 2009;284(2):1009-17. [Medline].

  18. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis. Oct 2003;42(4 Suppl 3):S1-201. [Medline].

  19. Fry AC, Singh DK, Chandna SM, Farrington K. Relative importance of residual renal function and convection in determining beta-2-microglobulin levels in high-flux haemodialysis and on-line haemodiafiltration. Blood Purif. 2007;25(3):295-302. [Medline].

  20. Balint E, Marshall CF, Sprague SM. Role of interleukin-6 in beta2-microglobulin-induced bone mineral dissolution. Kidney Int. Apr 2000;57(4):1599-607. [Medline].

  21. Dember LM, Jaber BL. Dialysis-related amyloidosis: late finding or hidden epidemic?. Semin Dial. Mar-Apr 2006;19(2):105-9. [Medline].

  22. Floege J, Ehlerding G. Beta-2-microglobulin-associated amyloidosis. Nephron. 1996;72(1):9-26. [Medline].

  23. Gallo G, Kaakour M, Kuman A. Immunohistologic classification of systemic amyloidosis by fat aspiration biopsy. Amyloid, International Journal of Experimental and Clinical Investigation. 1994;1:94-9.

  24. Garcia-Garcia M, Argiles, Gouin-Charnet A, Durfort M, Garcia-Valero J, Mourad G. Impaired lysosomal processing of beta2-microglobulin by infiltrating macrophages in dialysis amyloidosis. Kidney Int. Mar 1999;55(3):899-906. [Medline].

  25. Gejyo F. Beta 2-microglobulin amyloid. Amyloid. Mar 2000;7(1):17-8. [Medline].

  26. Gejyo F, Arakawa M. Beta 2-microglobulin-related amyloidosis: where do we stand?. Nephrol Dial Transplant. 1995;10(2):155-7. [Medline].

  27. Haase M, Bellomo R, Baldwin I, Haase-Fielitz A, Fealy N, Morgera S, et al. Beta2-microglobulin removal and plasma albumin levels with high cut-off hemodialysis. Int J Artif Organs. May 2007;30(5):385-92. [Medline].

  28. Jadoul M, Garbar C, Noel H, Sennesael J, Vanholder R, Bernaert P, et al. Histological prevalence of beta 2-microglobulin amyloidosis in hemodialysis: a prospective post-mortem study. Kidney Int. Jun 1997;51(6):1928-32. [Medline].

  29. Jadoul M, Garbar C, Vanholder R, Sennesael J, Michel C, Robert A, et al. Prevalence of histological beta2-microglobulin amyloidosis in CAPD patients compared with hemodialysis patients. Kidney Int. Sep 1998;54(3):956-9. [Medline].

  30. Kaplan B, Martin BM, Livoff A, Yeremenko D, Livneh A, Cohen HI. Gastrointestinal beta2microglobulin amyloidosis in hemodialysis patients: biochemical analysis of amyloid proteins in small formalin-fixed paraffin-embedded tissue specimens. Mod Pathol. Dec 2005;18(12):1610-7. [Medline].

  31. Kay J. Beta 2-microglobulin amyloidosis in renal failure: understanding this recently recognized condition. Cleve Clin J Med. Mar 1999;66(3):145-7. [Medline].

  32. Kay J. Review: Beta2-microglobulin amyloidosis. Int J Exp Clin Invest. 1997;4:187-211.

  33. Kazama JJ, Maruyama H, Gejyo F. Reduction of circulating beta2-microglobulin level for the treatment of dialysis-related amyloidosis. Nephrol Dial Transplant. 2001;16 Suppl 4:31-5. Review:[Medline].

  34. Miyata T, Ueda Y, Saito A, Kurokawa K. 'Carbonyl stress' and dialysis-related amyloidosis. Nephrol Dial Transplant. 2000;15 Suppl 1:25-8. [Medline].

  35. Nangaku M, Miyata T, Kurokawa K. Pathogenesis and management of dialysis-related amyloid bone disease. Am J Med Sci. Jun 1999;317(6):410-5. [Medline].

  36. Ritz E, Deppisch R, Stein G. Beta 2 microglobulin-derived amyloid in dialysis patients. Adv Exp Med Biol. 1989;260:11-8. [Medline].

  37. Varga J, Idelson BA, Felson D, Skinner M, Cohen AS. Lack of amyloid in abdominal fat aspirates from patients undergoing long-term hemodialysis. Arch Intern Med. Aug 1987;147(8):1455-7. [Medline].

 
Previous
Next
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.