eMedicine Specialties > Nephrology > Glomerular Diseases

Glomerulonephritis, Rapidly Progressive: Differential Diagnoses & Workup

Author: James W Lohr, MD, Fellowship Program Director, Professor, Department of Internal Medicine, Division of Nephrology, State University of New York at Buffalo
Coauthor(s): Kerry C Owens, MD, Consulting Staff, Department of Internal Medicine, Section of Nephrology, Integris Baptist Medical Center of Oklahoma City
Contributor Information and Disclosures

Updated: Sep 4, 2008

Differential Diagnoses

Amyloidosis, AA (Inflammatory)
Hypertension
Antiphospholipid Syndrome
Hypertension, Malignant
Churg-Strauss Syndrome
Light-Chain Deposition Disease
Cryoglobulinemia
Microscopic Polyangiitis
Glomerulonephritis, Diffuse Proliferative
Multiple Myeloma
Glomerulonephritis, Membranoproliferative
Nephritis, Lupus
Glomerulonephritis, Nonstreptococcal Associated With Infection
Polyarteritis Nodosa
Glomerulonephritis, Poststreptococcal
Wegener Granulomatosis
Goodpasture Syndrome

Workup

Laboratory Studies

  • The most important requirement in the diagnosis of ANCA-associated disease is a high index of suspicion. Rapid diagnosis is essential for organ preservation. Laboratory studies include the following:
    • CBC count with differential: Results are most likely normal, but anemia may be present if the patient has renal failure or is bleeding from the GI tract. Eosinophilia of 13% or greater is suggestive of Churg-Strauss disease.
    • Serum electrolytes, BUN, creatinine, lactate dehydrogenase (LDH), creatine phosphokinase (CPK), and liver function tests: The most common abnormality is an increased serum creatinine level. However, the level can be normal at presentation. Tissue enzyme (ie, lactate dehydrogenase, creatine kinase) levels may be elevated if the amount of inflammation is significant enough to result in myalgias.
    • Urinalysis with microscopy: Proteinuria is almost always present but is rarely greater than 2-3 g in 24 hours. Microscopic hematuria is invariably present and may be the only clue to renal disease at presentation. The presence of red cell casts indicates glomerular inflammation and is a very helpful clue.
    • Erythrocyte sedimentation rate: Although a nonspecific finding, the rate is usually elevated with active disease.
    • C-reactive protein: levels are elevated and correspond with disease activity.
    • Antinuclear antibody (ANA) titer: The ANA titer result is not positive in patients with ANCA-associated disease. A high ANA titer should direct the diagnosis toward systemic lupus erythematosus.
    • ANCA with ELISA subtyping: More than 80% of patients with microscopic polyangiitis are ANCA-positive, and most of these demonstrate pANCA with MPO specificity. Of patients with Wegener granulomatosis, 90% are ANCA-positive and most have cANCA with PR3 specificity, especially in pulmonary involvement. However, ANCA type and specificity is not pathognomonic for each of these clinical syndromes because some patients with Wegener granulomatosis are pANCA-positive and some patients with microscopic polyangiitis are cANCA-positive.
    • Cryoglobulins: The symptoms of cryoglobulinemia are very similar to those of ANCA-related disease. However, in persons with ANCA-related diseases, the cryoglobulin titer result should be negative.
    • Hepatitis profile: ANCA-associated disease is not associated with hepatitis. However, hepatitis B is associated with polyarteritis nodosa and hepatitis C is associated with mixed cryoglobulinemia.
    • Urine and serum protein electrophoresis: Perform this in any middle-aged or elderly person presenting with rapidly progressive glomerulonephritis to exclude the presence of light-chain disease or overt multiple myeloma as a cause of the clinical findings.

Imaging Studies

  • A renal ultrasound should be done to rule out obstructive uropathy in any patient with acute renal failure.
  • In patients with rapidly progressive glomerulonephritis, a renal ultrasound is done to establish the presence of 2 functioning kidneys prior to a percutaneous renal biopsy.

Procedures

  • Because the sensitivity and the specificity of ANCA testing for pauci-immune glomerulonephritis is only 80-90%, a renal biopsy is recommended to be performed on patients with rapidly progressive glomerulonephritis to establish a definite diagnosis and to determine the severity of the disease. The initiation of therapy should not be delayed for biopsy results to be obtained.

Histologic Findings

Renal biopsy specimens show a diffuse, proliferative, necrotizing glomerulonephritis with crescent formation.

More on Glomerulonephritis, Rapidly Progressive

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

  1. Davies DJ, Moran JE, Niall JF, et al. Segmental necrotising glomerulonephritis with antineutrophil antibody: possible arbovirus aetiology?. Br Med J (Clin Res Ed). Aug 28-Sep 4 1982;285(6342):606. [Medline].

  2. Hall JB, Wadham BM, Wood CJ, et al. Vasculitis and glomerulonephritis: a subgroup with an antineutrophil cytoplasmic antibody. Aust N Z J Med. Jun 1984;14(3):277-8. [Medline].

  3. Falk RJ, Hogan S, Carey TS, et al. Clinical course of anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis and systemic vasculitis. The Glomerular Disease Collaborative Network. Ann Intern Med. Nov 1 1990;113(9):656-63. [Medline].

  4. Nachman PH, Hogan SL, Jennette JC, et al. Treatment response and relapse in antineutrophil cytoplasmic autoantibody-associated microscopic polyangiitis and glomerulonephritis. J Am Soc Nephrol. Jan 1996;7(1):33-9. [Medline].

  5. Villa-Forte A, Clark TM, Gomes M, et al. Substitution of methotrexate for cyclophosphamide in Wegener granulomatosis: a 12-year single-practice experience. Medicine (Baltimore). Sep 2007;86(5):269-77. [Medline].

  6. Andrassy K, Kuster S, Waldherr R, et al. Rapidly progressive glomerulonephritis: analysis of prevalence and clinical course. Nephron. 1991;59(2):206-12. [Medline].

  7. Bacani RA, Velasquez F, Kanter A, et al. Rapidly progressive (nonstreptococcal) glomerulonephritis. Ann Intern Med. Sep 1968;69(3):463-85. [Medline].

  8. Couser WG. Rapidly progressive glomerulonephritis: classification, pathogenetic mechanisms, and therapy. Am J Kidney Dis. Jun 1988;11(6):449-64. [Medline].

  9. de Lind van Wijngaarden RA, Hauer HA, Wolterbeek R, et al. Chances of renal recovery for dialysis-dependent ANCA-associated glomerulonephritis. J Am Soc Nephrol. Jul 2007;18(7):2189-97. [Medline].

  10. Hogan SL, Nachman PH, Wilkman AS, et al. Prognostic markers in patients with antineutrophil cytoplasmic autoantibody-associated microscopic polyangiitis and glomerulonephritis. J Am Soc Nephrol. Jan 1996;7(1):23-32. [Medline].

  11. Hotta O, Ishida A, Kimura T, et al. Improvements in treatment strategies for patients with antineutrophil cytoplasmic antibody-associated rapidly progressive glomerulonephritis. Ther Apher Dial. Oct 2006;10(5):390-5. [Medline].

  12. Jayne DR, Gaskin G, Pusey CD, et al. ANCA and predicting relapse in systemic vasculitis. QJM. Feb 1995;88(2):127-33. [Medline].

  13. [Best Evidence] Jayne DR, Gaskin G, Rasmussen N, et al. Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J Am Soc Nephrol. Jul 2007;18(7):2180-8. [Medline].

  14. Jennette JC. Renal involvement in systemic vasculilits. In: Jennette JC, Olson JL, Schwartz MM, Silva FG, eds. Hepinstall's Pathology of the Kidney. 5th ed. Philadelphia: Lippincott-Raven; 1998:1059-94.

  15. Pusey CD, Rees AJ, Evans DJ, et al. Plasma exchange in focal necrotizing glomerulonephritis without anti-GBM antibodies. Kidney Int. Oct 1991;40(4):757-63. [Medline].

  16. Savige J, Davies D, Falk RJ, et al. Antineutrophil cytoplasmic antibodies and associated diseases: a review of the clinical and laboratory features. Kidney Int. Mar 2000;57(3):846-62. [Medline].

  17. Stilmant MM, Bolton WK, Sturgill BC, et al. Crescentic glomerulonephritis without immune deposits: clinicopathologic features. Kidney Int. Feb 1979;15(2):184-95. [Medline].

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Further Reading

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Keywords

rapidly progressive glomerulonephritis, RPGN, kidney disease, renal disease, kidney disorder, renal disorder, Wegener granulomatosis, WG, Wegener's granulomatosis, Churg-Strauss disease, CS, Churg-Strauss syndrome, CSS, CSD, microscopic polyangiitis, MPA, circulating antineutrophil cytoplasmic antibody associated glomerulonephritis, ANCA disease, ANCA-associated disease, ANCA glomerulonephritis, ANCA-associated vasculitis, fibrinoid necrosis, extensive crescent formation, pauci-immune disease, pauci immune disease, renal-limited necrotizing crescentic glomerulonephritis, NCGN, systemic lupus erythematosus, SLE, inflammatory bowel disease, IBD, sclerosing cholangitis, autoimmune hepatitis, rheumatoid arthritis, RA, Felty syndrome, Felty's syndrome, ANCA-associated vasculitides

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Contributor Information and Disclosures

Author

James W Lohr, MD, Fellowship Program Director, Professor, Department of Internal Medicine, Division of Nephrology, State University of New York at Buffalo
James W Lohr, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Society of Nephrology, and Central Society for Clinical Research
Disclosure: Nothing to disclose.

Coauthor(s)

Kerry C Owens, MD, Consulting Staff, Department of Internal Medicine, Section of Nephrology, Integris Baptist Medical Center of Oklahoma City
Kerry C Owens, MD is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Nephrology, International Society of Nephrology, Oklahoma State Medical Association, and Sigma Xi
Disclosure: Nothing to disclose.

Medical Editor

F John Gennari, MD, Director, Division of Nephrology, Associate Chair for Academic Affairs, Robert F and Genevieve B Patrick Professor, Department of Medicine, University of Vermont College of Medicine
F John Gennari, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Federation for Medical Research, American Heart Association, American Physiological Society, American Society for Clinical Investigation, American Society of Nephrology, and International Society of Nephrology
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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