Antiglomerular Basement Membrane Disease Workup

  • Author: Ramesh Saxena, MD, PhD; Chief Editor: Vecihi Batuman, MD, FACP, FASN   more...
 
Updated: Nov 21, 2011
 

Laboratory Studies

  • Urinalysis: A urinary dipstick test and a 24-hour urine collection to test for protein and creatinine should be performed for detection of hematuria and proteinuria. Urinary sediment should be analyzed using microscopy to detect dysmorphic red blood cells and cellular casts.
    • Hematuria: Urinary sediment frequently reveals dysmorphic red blood cells and red blood cell casts.
    • Proteinuria: This is usually absent in the early years of life. Proteinuria usually progresses with age and may be in the nephrotic range in up to 30% of patients.
  • Blood chemistry and CBC count
    • Blood chemistry: Patients usually have elevated blood urea nitrogen and serum creatinine levels. Serum bicarbonate levels are usually low, and serum phosphate levels may be elevated because of renal failure.
    • CBC count: This may show low hemoglobin and hematocrit levels, reflecting blood loss from pulmonary hemorrhage. Serial analysis may be helpful for monitoring blood loss. Low hemoglobin levels can also be due to advanced renal failure. The platelet count is usually within reference ranges. A mild leukocytosis is often observed.
  • Complement levels and serology
    • Complement: levels are usually within reference ranges.
    • Antineutrophil cytoplasmic antibodies (ANCA): These test findings are usually negative. However, approximately 25-30% patients with anti-GBM disease have circulating ANCA. Of these patients, approximately 75% have perinuclear ANCA; the remaining 25% have cytoplasmic ANCA.
    • Circulating anti-GBM antibodies: More than 95% of patients with anti-GBM nephritis have circulating anti-GBM antibodies. The antibodies are usually of the immunoglobulin G (IgG) class, although immunoglobulin A or immunoglobulin M anti-GBM antibodies are occasionally observed. They can be detected using indirect immunofluorescence assays, usually using monkey kidneys as the substrate, or by radioimmunoassay or enzyme-linked immunosorbent assay, which use human recombinant GBM antigens.[4] Radioimmunoassay and enzyme-linked immunosorbent assay (ELISA) are more sensitive and specific than indirect immunofluorescence assays. Currently, ELISA is most commonly used to help detect circulating anti-GBM antibodies. They are highly sensitive. However, their specificity varies depending upon the antigen used for the assay.[4]
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Imaging Studies

  • Renal ultrasound: In the early stages, renal ultrasound shows normal-sized kidneys. However, with advancing renal failure, the kidneys shrink and become echogenic.
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Procedures

  • Unless contraindicated, a renal biopsy should be promptly performed in every case. Rapid diagnosis is necessary to assess the degree of crescentic involvement and the extent of fibrosis and to exclude other disease processes. Furthermore, prompt diagnosis is essential in order to start specific treatment as early as possible to preserve renal function.
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Histologic Findings

Light microscopy reveals the presence of crescents in more than 95% of patients (see the image below), and approximately 80% of patients show crescents involving more than 50% glomeruli). In early stages, the crescents are cellular and associated with necrotizing glomerular lesions. They gradually evolve into fibrotic crescents and glomerular sclerosis. Focal rupture of the GBM and fibrinoid necrosis of glomeruli are usually observed. In severe cases, rupture of the Bowman capsule ensues. Tubulointerstitial changes, including interstitial edema and inflammation and tubular damage, are usually observed along with glomerular injury. If necrotizing inflammation is observed in arteries or arterioles, the possibility of concurrent ANCA-associated glomerulonephritis should be considered.

Light microscopy of kidney biopsy specimen from a Light microscopy of kidney biopsy specimen from a patient with antiglomerular basement membrane nephritis showing extensive crescent formation and the collapse of glomerular tuft.

Immunofluorescent examination of the biopsy specimen reveals the characteristic linear deposition of IgG (rarely immunoglobulin A or immunoglobulin M) antibodies along the GBM (as demonstrated in the image below). Linear staining for IgG may also occur along the tubular basement membrane. Weak linear staining of the GBM is frequently observed in persons with diabetic nephropathy, but clinical data and light microscopic features can easily distinguish the 2 conditions.

Immunofluorescent examination of a kidney biopsy sImmunofluorescent examination of a kidney biopsy specimen from a patient with antiglomerular basement membrane nephritis showing a linear deposition of immunoglobulin G along the glomerular basement membrane.

Electron microscopy findings reflect those observed with light microscopy and include the presence of crescents, disruption of the GBM, and cellular infiltration at the sites of necrosis.

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Contributor Information and Disclosures
Author

Ramesh Saxena, MD, PhD  Associate Professor, Department of Internal Medicine, Division of Nephrology, University of Texas Southwestern Medical Center

Ramesh Saxena, MD, PhD is a member of the following medical societies: American Medical Association, American Society of Nephrology, International Society of Nephrology, and National Kidney Foundation

Disclosure: e-medicine Honoraria authoring review articles

Specialty Editor Board

Chike Magnus Nzerue, MD  Associate Dean for Clinical Affairs, Vice-Chairman of Internal Medicine, Meharry Medical College

Chike Magnus Nzerue, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American College of Physicians-American Society of Internal Medicine, 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 Salary Employment

Christie P Thomas, MBBS, FRCP, FASN, FAHA  Professor, Department of Internal Medicine, Division of Nephrology, Medical Director, Kidney and Kidney/Pancreas Transplant Program, University of Iowa Hospitals and Clinics

Christie P Thomas, MBBS, FRCP, FASN, FAHA is a member of the following medical societies: American College of Physicians, American Federation for Medical Research, American Heart Association, American Society of Nephrology, American Society of Transplantation, American Thoracic Society, International Society of Nephrology, and Royal College of Physicians

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: 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.

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Light microscopy of kidney biopsy specimen from a patient with antiglomerular basement membrane nephritis showing extensive crescent formation and the collapse of glomerular tuft.
Immunofluorescent examination of a kidney biopsy specimen from a patient with antiglomerular basement membrane nephritis showing a linear deposition of immunoglobulin G along the glomerular basement membrane.
 
 
 
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