eMedicine Specialties > Nephrology > Glomerular Diseases

Glomerulonephritis, Membranoproliferative: Differential Diagnoses & Workup

Author: Pranay Kathuria, MD, MBBS, FACP, FASN, Chief, Section of Nephrology, Associate Professor of Medicine, Associate Director, Clinical Research Center, Schusterman Center, University of Oklahoma College of Medicine
Coauthor(s): Martin Senitko, MD, Fellow, Department of Internal Medicine, Division of Nephrology, University of Texas Southwestern Medical Center; Sandeep Singh, MD, Fellow, Department of Internal Medicine, Division of Nephrology, University of Texas Southwestern Medical Center
Contributor Information and Disclosures

Updated: Sep 4, 2008

Differential Diagnoses

Glomerulonephritis, Acute
Glomerulonephritis, Poststreptococcal
Glomerulonephritis, Rapidly Progressive
Nephritis, Lupus

Other Problems to Be Considered

Glomerulonephritis, fibrillary
IgA nephropathy
Vasculitis

Workup

Laboratory Studies

  • Urinalysis
    • Glomerular hematuria; characterized by dysmorphic red blood cells (RBCs) and RBC casts
    • Proteinuria is almost always present.
    • Urine protein creatinine ratio is a good estimate of 24-hour urinary protein excretion.
    • Nephrotic proteinuria is present in approximately 50% of patients.
  • Serum chemistries
    • Elevated serum creatinine and blood urine nitrogen and a decreased estimated glomerular filtration rate (GFR) are evident in 20-50% of patients at presentation. Patients with a nephritic presentation typically have a decreased GFR.
    • Hyperlipidemia and low albumin may be seen with nephrotic syndrome.
  • CBC count with differential: Most often, patients have a normocytic normochromic anemia.
  • Complement profile - Membranoproliferative glomerulonephritis type I
    • C3 levels are low in about half of the patients.
    • Evidence of activation of the classic pathway of complement (ie, low C4, C2, C1q, B, C3)
    • Terminal complement components C3, C5, C8, and C9 may be low or within the reference range.
    • NFc (C4NeF) or NFt may be present.
  • Complement profile - Membranoproliferative glomerulonephritis type II
    • C3 levels are low in 70-80% of patients.
    • Early and terminal complement components are within the reference range.
    • NFa (C3NeF) is present in more than 70% of patients.
    • Factor H levels may be low.
  • Complement profile - Membranoproliferative glomerulonephritis type III
    • C3 levels are decreased in 50% of patients.
    • C1q and C4 levels are within the reference range.
    • Terminal complement components are low, especially if C3 is markedly depressed.
    • NFa is absent and NFt is present in 60-80% of patients.
    • Antistreptolysin-O (ASO) titers may be elevated in as many as 50% of patients at presentation.
  • To rule out secondary causes, obtain antinuclear antibodies, hepatitis screens, cryoglobulins, urine, and serum protein electrophoresis.

Procedures

  • Perform a kidney biopsy for definitive diagnosis.

Histologic Findings

Light microscopy

Glomeruli generally are enlarged and hypercellular, with an increase in mesangial cellularity and matrix. Mesangial increase, when generalized throughout the glomeruli, causes an exaggeration of their lobular form, giving rise to the alternative name of lobular nephritis. Infiltrating neutrophils and monocytes contribute to glomerular hypercellularity.

The capillary basement membranes are thickened by interposition of mesangial cells and matrix into the capillary wall. This gives rise to the tram-track or double-contoured appearance of the capillary wall, best appreciated with the methenamine silver stain or the periodic acid-Schiff reagent.

Crescents may be visible in 10% of patient biopsy specimens. Interstitial changes, including inflammation, interstitial fibrosis, and tubular atrophy, are observed in patients with progressive decline in GFR.

Membranoproliferative glomerulonephritis type I

On electron microscopy, electron dense deposits in subendothelial sites are characteristic of this disease. Mesangial and occasional subepithelial deposits also may be present. Irregular new basement membrane material is formed around the subendothelial deposits and mesangial projections, producing the tram-track appearance on light microscopy.

By immunofluorescence, prominent C3 deposition in a granular pattern is noted in the capillary walls, with variable mesangial C3 deposits. Early components of complement, immunoglobulin G (IgG), and, less commonly, immunoglobulin M (IgM) may be found in a distribution similar to C3.

Membranoproliferative glomerulonephritis type II or dense deposit disease

The basement membranes of the glomerulus, Bowman capsule, tubules, and peritubular capillaries are thickened. The basement membrane appears irregular and ribbonlike on special stains (eg, periodic acid-Schiff, thioflavine-T, toluidine blue).

On electron microscopy, the basement membrane is thickened by discontinuous, amorphous electron dense deposits that reside in the lamina densa layer, hence the alternative name of dense deposit disease. Mesangial and subepithelial dense deposits may be noted.

Immunofluorescence reveals complement component C3 deposited in an irregular granular pattern in the basement membranes on either side but not within the dense deposits or in nodular ring forms in the mesangium. Little or no deposition of immunoglobulins occurs in the glomeruli.

Membranoproliferative glomerulonephritis type III

This variant of membranoproliferative glomerulonephritis, also called the Burkholder variant, displays combined features of membranoproliferative glomerulonephritis type I and membranous nephropathy.

Subepithelial, subendothelial, and mesangial deposits are present on electron microscopy. Successive generations of subendothelial and subepithelial deposits disrupt the basement membrane, and concurrent formation of new lamina densa material is present, giving the basement membrane a complex laminated appearance.

Immunohistology shows granular deposition of C3, C5, properdin, IgG, and IgM, predominantly in the capillary walls.

More on Glomerulonephritis, Membranoproliferative

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

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Further Reading

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Keywords

membranoproliferative glomerulonephritis, MPGN, mesangiocapillary glomerulonephritis, lobular glomerulonephritis, persistent hypocomplementemic glomerulonephritis, parietoproliferative glomerulonephritis, dense deposit disease, lobular nephritis

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Contributor Information and Disclosures

Author

Pranay Kathuria, MD, MBBS, FACP, FASN, Chief, Section of Nephrology, Associate Professor of Medicine, Associate Director, Clinical Research Center, Schusterman Center, University of Oklahoma College of Medicine
Pranay Kathuria, MD, MBBS, FACP, FASN is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, American Heart Association, American Society of Hypertension, American Society of Nephrology, and National Kidney Foundation
Disclosure: Nothing to disclose.

Coauthor(s)

Martin Senitko, MD, Fellow, Department of Internal Medicine, Division of Nephrology, University of Texas Southwestern Medical Center
Martin Senitko, MD is a member of the following medical societies: American College of Physicians and American Society of Nephrology
Disclosure: Nothing to disclose.

Sandeep Singh, MD, Fellow, Department of Internal Medicine, Division of Nephrology, University of Texas Southwestern Medical Center
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

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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