eMedicine Specialties > Nephrology > The Kidney in Systemic Diseases

Amyloidosis, Beta2M (Dialysis-Related): Differential Diagnoses & Workup

Author: Anita Basu, MD, Assistant Professor of Medicine, University of Mississippi School of Medicine; Staff Nephrologist, GV (Sonny) Montgomery Veterans Affairs Medical Center
Coauthor(s): Carol A Bogdan, MD, Consulting Staff, Coastal Cancer Center, Myrtle Beach, SC; Reynaldo Matute, MD, Clinical Assistant Professor, Department of Internal Medicine, Division of Nephrology, New York Medical College
Contributor Information and Disclosures

Updated: Feb 22, 2008

Differential Diagnoses

Amyloidosis, Familial Renal
Amyloidosis, Immunoglobulin-Related
Amyloidosis, Transthyretin-Related

Other Problems to Be Considered

Secondary hyperparathyroidism is the most common bone disease found in patients with end-stage renal disease. Bone erosions, tendon ruptures, and osteosclerosis can be the source of bone pain or polyarthralgias. DRA bone lesions differ from renal osteodystrophy in that the presence of the amyloid deposits interfere with normal bone tissue dynamics while in renal osteodystrophy, the abnormality is in the underlying metabolic process itself, causing bone turnover to be either increased or decreased. In the case of pathological fractures in patients on dialysis, it is essential that DRA be distinguished from renal osteodystrophy because there are implications for healing.

Aluminum overload: Patients with end-stage renal disease sometimes receive aluminum-containing antacids to control serum phosphate levels. Absorbed aluminum can be toxic to osteoblasts, leading to the development of osteomalacia.

Dupuytren contracture is a type of palmar fasciitis observed in people with chronic alcoholism and people with chronic diabetes.

Workup

Laboratory Studies

  • The diagnosis of beta-2-microglobulin amyloidosis is established primarily by its clinical appearance on tissue or bone biopsy.
  • Blood  
    • The reference range of the serum concentration of beta-2-microglobulin is 1.5-3 mg/L. Serum levels of beta-2-microglobulin can be elevated to values of 50-100 mg/L. Beta-2-microglobulin levels correlate with elevated serum creatinine levels and are inversely related to the glomerular filtration rate.
    • Hematologic findings frequently reveal a normochromic, normocytic anemia.

Imaging Studies

  • Radiographs: Radiologic lesions typically present prior to the onset of pain. Joint erosions (usually involving large joints), lytic and cystic bone lesions (typically juxta-articular), pathological 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.
  • CT scans reveal amyloid deposits of intermediate attenuation. CT scans can be used to identify pseudotumors and pseudocystic areas in the juxta-articular bone. CT 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.
  • 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, and sonographic studies.
  • Ultrasound is useful in the detection of tendon thickness. Rotator cuff thickness greater than 8 mm, thickening of joint capsules (especially of the hip and knee), and retention of synovial fluid may be observed.

Other Tests

  • Electron microscopy: Typically, 8- to 10-nm wide, nonbranching, curvilinear fibrils are observed.
  • Scintigraphy (radiolabeled P-component scans, including iodine I 123 serum amyloid P and iodohippurate sodium I 131 beta-2-microglobulin and the more natural I 111 beta-2-microglobulin) detects involved lesions using local deposition of tracers. The cells surrounding the amyloid deposit take up the circulating tracer, making it 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.

Procedures

  • Biopsy with Congo red staining and with immunostaining  
    • The criterion standard for diagnosis is histological 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. Unlike other types of amyloidosis, rectal biopsy and subcutaneous fat aspiration are of little value. The most common site from which biopsies are obtained is the sternoclavicular joint.
    • Immunohistochemical reaction of biopsy specimen: Antisera to Abeta-2-microglobulin are taken up by the Congo red–positive areas but not by other types of amyloidosis.

Histologic Findings

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-2-microglobulin antibody confirms the diagnosis of beta-2-microglobulin amyloidosis.

More on Amyloidosis, Beta2M (Dialysis-Related)

Overview: Amyloidosis, Beta2M (Dialysis-Related)
Differential Diagnoses & Workup: Amyloidosis, Beta2M (Dialysis-Related)
Treatment & Medication: Amyloidosis, Beta2M (Dialysis-Related)
Follow-up: Amyloidosis, Beta2M (Dialysis-Related)
References
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References

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Further Reading

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Keywords

dialysis-related amyloidosis, DRA, hemodialysis-associated amyloidosis, beta2 -microglobulin amyloidosis, beta-2-microglobulin amyloidosis, hemodialysis, HD, continuous ambulatory peritoneal dialysis, CAPD, near end-stage renal disease, carpal tunnel syndrome, flexor tenosynovitis, trigger finger, trigger thumb, scapulohumeral arthropathy, spondyloarthropathy, bone cysts, pathologic fractures, bone cysts

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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.

Medical Editor

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.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

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.

CME Editor

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 Osteopathic Internists, 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; Genzyme Honoraria Consulting; Roche Honoraria Consulting

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.

 
 
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