Medscape is available in 5 Language Editions – Choose your Edition here.


Dialysis-Related Beta-2m Amyloidosis Workup

  • Author: Anita Basu, MD, FACP; Chief Editor: Vecihi Batuman, MD, FACP, FASN  more...
Updated: May 01, 2014

Approach Considerations

The diagnosis of beta-2m amyloidosis is established primarily by its clinical appearance on tissue or bone biopsy.

Obtaining a biopsy of the affected bone or synovium, followed by routine hematoxylin and eosin staining, reveals homogeneous eosinophilic material. Amyloid deposits are positive for Congo red staining, showing green birefringence of the amyloid fibrils under polarized light. Specific immunostaining of amyloid deposits by monoclonal anti ̶ beta-2m antibody confirms the diagnosis of beta-2m amyloidosis.

Antisera to amyloid beta-2m are taken up by the Congo red–positive areas, but are not taken up in other types of amyloidosis.

Blood tests

The reference range of the serum concentration of beta-2m is 1.5-3 mg/L, while in amyloidosis, serum levels can be elevated to values of 50-100 mg/L. However, an increase in beta-2m levels does not diagnose beta-2 amyloidosis as these levels are usually elevated with low glomerular filtration rates. Hematologic findings frequently reveal a normochromic, normocytic anemia.

Electron microscopy

Typically, 8-10 nm wide, nonbranching, curvilinear fibrils are observed in beta-2m amyloidosis.


Imaging Studies


Radiologic lesions typically present prior to the onset of pain. Joint erosions (usually involving large joints), lytic and cystic bone lesions (typically juxta-articular), pathologic fractures (most commonly involving the femoral head), spondyloarthropathies (usually involving the cervical area), and vertebral compression fractures may be observed. However, conventional radiography may underestimate the extent of the disease.[13]

CT scanning

Computed tomography (CT) scans reveal amyloid deposits of intermediate attenuation. CT scans can also be used to identify pseudotumors and pseudocystic areas in the juxta-articular bone. Moreover, CT scanning is the best method for detecting small areas of osteolysis in cortical bone or osseous erosion, and it may be helpful in the assessment of the distribution and extent of destructive changes.[13]


Magnetic resonance imaging (MRI) shows characteristic long T1 and short T2 relaxation times, resulting in low to intermediate signal intensity. MRI is helpful in differentiating destructive spondyloarthropathies from inflammatory processes and infections. In evaluating amyloidosis, MRI may provide considerably more information than that obtained from conventional radiographic, CT scan, and sonographic studies.[13]


Ultrasonography is useful in the detection of tendon thickness. Rotator cuff thickness greater than 8mm, thickening of joint capsules (especially of the hip and knee), and retention of synovial fluid may be observed.



Scintigraphy in the diagnosis of beta-2m amyloidosis employs radiolabeled P-component scans, including iodine-123 (123 I) serum amyloid P, iodohippurate sodium (131 I) beta-2m, and the more natural111 I beta-2m.

The cells surrounding the amyloid deposit take up the circulating tracer, making scintigraphy a useful means of evaluating the total body burden of amyloid. This method has primarily been used in Europe and is not available in North America for diagnosing beta-2m amyloidosis.



The criterion standard for diagnosis is histologic identification using Congo red and immunohistochemical staining of biopsy specimens or centrifuged synovial fluid sediments. Puncture biopsies are obtained from cystic bone lesions and intra-articularly in synovia. In contrast to other types of amyloidosis, rectal biopsy and subcutaneous fat aspiration are of little value in diagnosing beta-2m amyloidosis. The most common site from which biopsies are obtained is the sternoclavicular joint.

Contributor Information and Disclosures

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

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

Disclosure: Nothing to disclose.


Carol A Bogdan, MD Consultant in Hematology-Oncology, 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, National Kidney Foundation

Disclosure: Nothing to disclose.

Chief Editor

Vecihi Batuman, MD, FACP, FASN Huberwald Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Renal Section, 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, International Society of Nephrology

Disclosure: Nothing to disclose.


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.

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 Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Reference Salary Employment

  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. 1999 Jun. 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. 2005 Nov-Dec. 29(6):483-91. [Medline].

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

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

  6. 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. 1996 Sep 1. 98(5):1088-94. [Medline].

  7. 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].

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

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

  10. 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. 2008 Dec. 70(6):496-502. [Medline].

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

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

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

  14. 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].

  15. 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].

  16. 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. 2000 Feb 28. 739(1):73-80. [Medline].

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

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

  19. 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. 2009 Jan 9. 284(2):1009-17. [Medline].

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

  21. Dember LM, Jaber BL. Dialysis-related amyloidosis: late finding or hidden epidemic?. Semin Dial. 2006 Mar-Apr. 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. 1999 Mar. 55(3):899-906. [Medline].

  25. Gejyo F. Beta 2-microglobulin amyloid. Amyloid. 2000 Mar. 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. 2007 May. 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. 1997 Jun. 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. 1998 Sep. 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. 2005 Dec. 18(12):1610-7. [Medline].

  31. Kay J. Beta 2-microglobulin amyloidosis in renal failure: understanding this recently recognized condition. Cleve Clin J Med. 1999 Mar. 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. 1999 Jun. 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. 1987 Aug. 147(8):1455-7. [Medline].

All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.