Dialysis-Related Beta-2m Amyloidosis Treatment & Management
- Author: Anita Basu, MD, FACP; Chief Editor: Vecihi Batuman, MD, FACP, FASN more...
At present, no adequate treatment of beta-2m amyloidosis exists. Medical therapy is limited to symptomatic approaches to ameliorating joint pain and inflammation. Conservative treatment includes physical and occupational therapy. Wrist splints, cervical collars, lumbar corsets, knee braces, and immobilization for spondyloarthropathies often are helpful.
The treatment of joint pain includes the use of nonsteroidal anti-inflammatory drugs (NSAIDs), intra-articular injections of prednisolone, 10% hydrocortisone cream, and, in severe cases, low-dose oral prednisone.
Surgical intervention—including carpal tunnel release with surgical decompression of the median nerve or release of the transverse carpal ligaments under endoscopic visualization, flexor tenosynovectomy or percutaneous first annular pulley release, spinal stabilization or laminectomy, or total joint replacement—may be effective in alleviating pain and restoring function.
Unfortunately, orthopedic interventions have high failure rates in DRA compared with rates in the general population. If, during the course of a surgery, beta-2m amyloidosis is suspected, then a biopsy should be performed at that time.
Involve rheumatologic, surgical, and transplant consultants early.
A nephrologist should care for patients with beta-2m amyloidosis on an ongoing basis.
Renal transplantation is the treatment of choice for beta-2m amyloidosis. It lowers the blood concentration of beta-2m to the reference range, halting the progression of the disease.
Osteoarticular symptoms, such as joint pain, swelling, and stiffness, disappear within the first week after transplantation. Cystic lesions usually remain unchanged, and regression of amyloid deposits probably does not occur.
Transplantation is not an option for all patients. Some patients on long-term dialysis will have undergone unsuccessful renal transplantation before they first developed beta-2m amyloidosis; in certain other cases, patients are not suitable candidates.
Although preventive measures are hard to assess, possible ways of preventing, or at least decreasing, the incidence of DRA are the use of a high-flux dialyzer, online hemodiafiltration, ultrapure dialysate, and adsorbent columns.
Based on guidelines from the Disease Outcomes Quality Initiative (DOQI), there are no indications for the routine monitoring of beta-2m.
High-flux biocompatible polyacrylonitrile and polysulfone membranes have increased middle molecule removal and have thereby enhanced beta-2m removal during HD and hemofiltration.
Online hemodiafiltration has been associated with maximal removal of beta-2m.
Ultrapure dialysate preparations
The use of ultrapure, sterile, and apyrogenic dialysate may aid in decreasing stimulation and in releasing cytokines. It also may decrease plasma levels of acute-phase proteins.
Direct hemoperfusion-type adsorption column (Lixelle)
This was developed to selectively eliminate beta-2m from the circulating blood of patients with DRA. Lixelle treatments reduce the circulating levels of beta-2m and inflammatory cytokines, thereby improving the symptoms of patients with DRA. While this therapy has been used and studied in Japan, it is not currently employed in the United States.[16, 18]
Studies examining the use of laser-beam irradiation to destroy amyloid fibrils of beta-2m fragments have been performed in Japan. This technique has implications for the prevention of amyloid fibril deposition and for the destruction of preformed amyloid deposits.
Drueke TB. Beta2-microglobulin and amyloidosis. Nephrol Dial Transplant. 2000. 15 Suppl 1:17-24. [Medline].
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].
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].
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].
Thornalley PJ. Glycation free adduct accumulation in renal disease: the new AGE. Pediatr Nephrol. 2005 Nov. 20(11):1515-22. [Medline].
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].
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].
Danesh F, Ho LT. Dialysis-related amyloidosis: history and clinical manifestations. Semin Dial. 2001 Mar-Apr;14(2):80-5. [Medline].
Kelly A, Apostle K, Sanders D, Bailey H. Musculoskeletal pain in dialysis-related amyloidosis. Can J Surg. 2007 Aug. 50(4):305-6. [Medline].
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].
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].
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].
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].
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].
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].
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].
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].
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].
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].
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].
Dember LM, Jaber BL. Dialysis-related amyloidosis: late finding or hidden epidemic?. Semin Dial. 2006 Mar-Apr. 19(2):105-9. [Medline].
Floege J, Ehlerding G. Beta-2-microglobulin-associated amyloidosis. Nephron. 1996. 72(1):9-26. [Medline].
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.
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].
Gejyo F. Beta 2-microglobulin amyloid. Amyloid. 2000 Mar. 7(1):17-8. [Medline].
Gejyo F, Arakawa M. Beta 2-microglobulin-related amyloidosis: where do we stand?. Nephrol Dial Transplant. 1995. 10(2):155-7. [Medline].
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].
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].
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].
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].
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].
Kay J. Review: Beta2-microglobulin amyloidosis. Int J Exp Clin Invest. 1997. 4:187-211.
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].
Miyata T, Ueda Y, Saito A, Kurokawa K. Carbonyl stress' and dialysis-related amyloidosis. Nephrol Dial Transplant. 2000. 15 Suppl 1:25-8. [Medline].
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].
Ritz E, Deppisch R, Stein G. Beta 2 microglobulin-derived amyloid in dialysis patients. Adv Exp Med Biol. 1989. 260:11-8. [Medline].
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].