Membranoproliferative glomerulonephritis
| Membranoproliferative glomerulonephritis | |
| ICD-10 | N00-N08 with .2 suffix |
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| ICD-9 | 581.2, 582.2, 583.2 |
| MeSH | D015432 |
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Differentiating Membranoproliferative glomerulonephritis from other Diseases |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]
Overview
Membranoproliferative glomerulonephritis or MPGN is a type of glomerulonephritis caused by immune complexes depositing in the kidney glomerular mesangium and basement membrane (GBM), activating complement and damaging the glomeruli. The GBM is rebuilt ontop of the deposits, causing a "tram-tracking" appearance under the microscope.
Diagnosis
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 with differential: Most often, patients have a normocytic normochromic anemia.
- Complement profile - MPGN 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 - MPGN 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.
- Complement profile - MPGN 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.
Other Diagnostic Procedures
- 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 MPGN, also called the Burkholder variant, displays combined features of MPGN 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.