eMedicine Specialties > Nephrology > Glomerular Diseases

Glomerulonephritis, Membranous: Differential Diagnoses & Workup

Author: Abeera Mansur, MD, Consultant Nephrologist, Doctors Hospital and Medical Center, Pakistan
Contributor Information and Disclosures

Updated: Dec 16, 2008

Differential Diagnoses

Focal Segmental Glomerulosclerosis
Glomerulonephritis, Membranoproliferative
Minimal-Change Disease

Other Problems to Be Considered

Secondary causes of membranous nephropathy

Workup

Laboratory Studies

  • Urine microscopy: Urine sediment is typically nephrotic, with oval fat bodies and fatty casts; however, in mild cases, the urinalysis may reveal proteinuria without formed elements in the sediment.
  • Serum creatinine
  • Blood urea nitrogen
  • Serum albumin
  • Proteinuria (quantitative) with a 24-hour urine collection: A ratio of spot urine protein to creatinine is easier to obtain, and the findings may be sufficient for screening purposes.
  • Creatinine clearance
  • Antinuclear antibodies
  • Anti–double-strand DNA, if results from antinuclear antibody testing are positive
  • Hepatitis B serology (if positive, DNA quantitation)
  • Hepatitis C (if positive, RNA quantitation)
  • Syphilis serology
  • Complement levels
  • Cryoglobulin, particularly if hepatitis C and/or low levels of complement are found
  • Lipid profile
  • Urinary C5b-9
  • Urinary beta-2 microglobulin (worse prognosis with an increased level)
  • Malignancy workup: An exhaustive workup for malignancy is not recommended because most cases of membranous nephropathy are not associated with cancer. However, because some increase in the rate of occult malignancy is recognized in patients with newly diagnosed membranous nephropathy, (1) ensure that age-appropriate health screening (eg, mammography, sigmoidoscopy) has been performed, and (2) investigate any clues from the initial patient history and physical examination.

Imaging Studies

  • Sonogram

Procedures

  • Renal biopsy: Definitive diagnosis is made based on findings from a renal biopsy.

Histologic Findings

Pathologic features can be observed using light microscopy, immunofluorescence microscopy, and electron microscopy.

  • Light microscopy: The mesangium is normal, with no hypercellularity. All glomeruli are involved. The capillary walls are thickened with patent capillary lumina. Subepithelial deposits are seen; with trichrome stain, they are shown to have spikes.
  • Immunofluorescence microscopy: Use strong granular capillary wall staining for immunoglobulin G (IgG), with C3 and both kappa and lambda light chains.
  • Electron microscopy
    • A considerable diversity of prognosis is seen with idiopathic membranous nephropathy. In a study of 105 patients with idiopathic membranous nephropathy, 2 different groups were identified on the electron microscopic findings. In the homogeneous type, only 1 patient developed end-stage renal failure, and earlier remission occurred in this group. With regard to secondary outcome, increased age, focal segmental glomerular sclerosis, arteriolosclerosis, and heterogeneous type of electron microscopic findings were independent risk factors.
    • Stage 1: Features appear normal using light microscopy, but, with electron microscopy, a few electron-dense deposits are seen along the capillary walls.
    • Stage 2: Numerous and larger deposits with spikes are seen.
    • Stage 3: New extracellular material surrounds the deposits.
    • Stage 4: Initial electron-dense deposits become electron-lucent, and capillary walls become thickened.

More on Glomerulonephritis, Membranous

Overview: Glomerulonephritis, Membranous
Differential Diagnoses & Workup: Glomerulonephritis, Membranous
Treatment & Medication: Glomerulonephritis, Membranous
Follow-up: Glomerulonephritis, Membranous
References

References

  1. Ronco P, Debiec H. New insights into the pathogenesis of membranous glomerulonephritis. Curr Opin Nephrol Hypertens. May 2006;15(3):258-63. [Medline].

  2. Chen A, Frank R, Vento S, et al. Idiopathic membranous nephropathy in pediatric patients: presentation, response to therapy, and long-term outcome. BMC Nephrol. Aug 6 2007;8:11. [Medline].

  3. El Kossi M, Harmer A, Goodwin J, et al. De novo membranous nephropathy associated with donor-specific alloantibody. Clin Transplant. Jan-Feb 2008;22(1):124-7. [Medline].

  4. Polenakovic M, Grcevska L, Dzikova S. 20 years after methylprednisolone/chlorambucil treatment in idiopathic membranous nephropathy stage II-III with nephrotic syndrome. Prilozi. Dec 2006;27(2):5-12. [Medline].

  5. Branten AJ, du Buf-Vereijken PW, Vervloet M, et al. Mycophenolate mofetil in idiopathic membranous nephropathy: a clinical trial with comparison to a historic control group treated with cyclophosphamide. Am J Kidney Dis. Aug 2007;50(2):248-56. [Medline].

  6. Ruggenenti P, Cravedi P, Remuzzi G. Latest treatment strategies for membranous nephropathy. Expert Opin Pharmacother. Dec 2007;8(18):3159-71. [Medline].

  7. Cravedi P, Ruggenenti P, Sghirlanzoni MC, et al. Titrating rituximab to circulating B cells to optimize lymphocytolytic therapy in idiopathic membranous nephropathy. Clin J Am Soc Nephrol. Sep 2007;2(5):932-7. [Medline].

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  10. [Best Evidence] Troyanov S, Roasio L, Pandes M, et al. Renal pathology in idiopathic membranous nephropathy: a new perspective. Kidney Int. May 2006;69(9):1641-8. [Medline].

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  14. Cunningham PN, Quigg RJ. Contrasting roles of complement activation and its regulation in membranous nephropathy. J Am Soc Nephrol. May 2005;16(5):1214-22. [Medline].

  15. Haas M, Meehan SM, Karrison TG, et al. Changing etiologies of unexplained adult nephrotic syndrome: a comparison of renal biopsy findings from 1976-1979 and 1995-1997. Am J Kidney Dis. Nov 1997;30(5):621-31. [Medline].

  16. Hogan SL, Muller KE, Jennette JC, et al. A review of therapeutic studies of idiopathic membranous glomerulopathy. Am J Kidney Dis. Jun 1995;25(6):862-75. [Medline].

  17. Honkanen E, Tornroth T, Gronhagen-Riska C. Natural history, clinical course and morphological evolution of membranous nephropathy. Nephrol Dial Transplant. 1992;7 Suppl 1:35-41. [Medline].

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  19. Kuroki A, Iyoda M, Shibata T, et al. Th2 cytokines increase and stimulate B cells to produce IgG4 in idiopathic membranous nephropathy. Kidney Int. Jul 2005;68(1):302-10. [Medline].

  20. Lin CY. Treatment of hepatitis B virus-associated membranous nephropathy with recombinant alpha-interferon. Kidney Int. Jan 1995;47(1):225-30. [Medline].

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  23. Ponticelli C, Zucchelli P, Passerini P, et al. A 10-year follow-up of a randomized study with methylprednisolone and chlorambucil in membranous nephropathy. Kidney Int. Nov 1995;48(5):1600-4. [Medline].

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Further Reading

Keywords

membranous glomerulonephritis, membranous nephropathy, nephrotic syndrome

Contributor Information and Disclosures

Author

Abeera Mansur, MD, Consultant Nephrologist, Doctors Hospital and Medical Center, Pakistan
Abeera Mansur, MD is a member of the following medical societies: American College of Physicians and American Society of Nephrology
Disclosure: Nothing to disclose.

Medical Editor

James H Sondheimer, MD, Director of Hemodialysis Unit, Harper Hospital; Associate Professor, Department of Internal Medicine, Division of Nephrology, Wayne State University School of Medicine
James H Sondheimer, MD is a member of the following medical societies: American College of Physicians and American Society of Nephrology
Disclosure: Nothing to disclose.

Pharmacy Editor

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

Managing Editor

Ajay K Singh, MB, MRCP, MBA, Associate Professor of Medicine, Director of Dialysis, Department of Medicine, Harvard Medical School; Clinical Chief of Renal Division, Brigham and Women's Hospital
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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