(See also Overview of Nephrotic Syndrome Overview of Nephrotic Syndrome Nephrotic syndrome is urinary excretion of > 3 g of protein/day due to a glomerular disorder plus edema and hypoalbuminemia. It is more common among children and has both primary and secondary... read more .)
Membranoproliferative glomerulonephritis is a group of immune-mediated disorders characterized histologically by glomerular basement membrane (GBM) thickening and proliferative changes on light microscopy. There are 3 types, each of which may have primary (idiopathic) or secondary causes. Primary forms affect children and young adults between ages 8 and 30 and account for 10% of cases of nephrotic syndrome in children; secondary forms tend to affect adults > 30. Men and women are affected equally. Reported familial cases of some types suggest genetic factors play a role in at least some cases. Many factors contribute to hypocomplementemia.
Membranoproliferative glomerulonephritis type I
Type I (mesangial proliferation with immune deposits) accounts for 80 to 85% of cases. The idiopathic form is rare. Type I most commonly occurs secondary to one of the following:
Systemic immune complex disorder (eg, systemic lupus erythematosus Systemic Lupus Erythematosus (SLE) Systemic lupus erythematosus is a chronic, multisystem, inflammatory disorder of autoimmune etiology, occurring predominantly in young women. Common manifestations may include arthralgias and... read more , mixed cryoglobulinemia, Sjögren syndrome Sjögren Syndrome Sjögren syndrome is a relatively common chronic, autoimmune, systemic, inflammatory disorder of unknown cause. It is characterized by dryness of the mouth, eyes, and other mucous membranes ... read more )
Chronic infection (eg, bacterial endocarditis Infective Endocarditis Infective endocarditis is infection of the endocardium, usually with bacteria (commonly, streptococci or staphylococci) or fungi. It may cause fever, heart murmurs, petechiae, anemia, embolic... read more , HIV infection Human Immunodeficiency Virus (HIV) Infection Human immunodeficiency virus (HIV) infection results from 1 of 2 similar retroviruses (HIV-1 and HIV-2) that destroy CD4+ lymphocytes and impair cell-mediated immunity, increasing risk of certain... read more , hepatitis B or C infection Causes of Hepatitis Hepatitis is inflammation of the liver characterized by diffuse or patchy necrosis. Hepatitis may be acute or chronic (usually defined as lasting > 6 months). Most cases of acute viral hepatitis... read more , visceral abscess, ventriculoatrial shunt infection)
Cancer (eg, chronic lymphocytic leukemia Chronic Lymphocytic Leukemia (CLL) Chronic lymphocytic leukemia (CLL) is characterized by progressive accumulation of phenotypically mature malignant B lymphocytes. Primary sites of disease include peripheral blood, bone marrow... read more , lymphomas Overview of Lymphoma Lymphomas are a heterogeneous group of tumors arising in the reticuloendothelial and lymphatic systems. The major types are Hodgkin lymphoma Non-Hodgkin lymphoma See table Comparison of Hodgkin... read more , melanoma Melanoma Malignant melanoma arises from melanocytes in a pigmented area (eg, skin, mucous membranes, eyes, or central nervous system). Metastasis is correlated with depth of dermal invasion. With spread... read more )
Other disorders (eg, partial lipodystrophy, C2 or C3 deficiencies, sarcoidosis Sarcoidosis Sarcoidosis is an inflammatory disorder resulting in noncaseating granulomas in one or more organs and tissues; etiology is unknown. The lungs and lymphatic system are most often affected, but... read more , thrombotic microangiopathies)
Dense deposit disease (membranoproliferative glomerulonephritis type II)
Type II (similar to type I with less mesangial proliferation and with GBM dense deposits) accounts for 15 to 20%. It is probably an autoimmune disorder in which an IgG autoantibody (C3 nephritic factor) binds C3 convertase, rendering C3 resistant to inactivation; immunofluorescent staining identifies C3 around dense deposits and in mesangium.
Membranoproliferative glomerulonephritis type III
Type III is thought to be a disorder similar to type I and accounts for few cases. Cause is unknown but may be related to immune complex (IgG, C3) deposition. An IgG autoantibody against the terminal component of complement is found in 70% of patients. Subepithelial deposits can occur focally and appear to disrupt the GBM.
Symptoms and Signs
Symptoms and signs are those of nephrotic syndrome Symptoms and Signs Nephrotic syndrome is urinary excretion of > 3 g of protein/day due to a glomerular disorder plus edema and hypoalbuminemia. It is more common among children and has both primary and secondary... read more in 60 to 80% of cases. Symptoms and signs of nephritic syndrome Acute glomerulonephritis Nephritic syndrome is defined by hematuria, variable degrees of proteinuria, usually dysmorphic red blood cells (RBCs), and often RBC casts on microscopic examination of urinary sediment. Often... read more (acute glomerulonephritis) are presenting features in 15 to 20% of cases of type I and III disease and in a higher percentage of type II disease. At diagnosis, 30% of patients have hypertension Hypertension Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more and 20% have renal insufficiency; hypertension often develops even before glomerular filtration rate (GFR) declines.
Patients with type II disease have a greater incidence of ocular abnormalities (basal laminar drusen, diffuse retinal pigment alterations, diskiform macular detachment, choroidal neovascularization), which ultimately impair vision.
Serum complement profile
Diagnosis is confirmed by renal biopsy Renal biopsy Biopsy of the urinary tract requires a trained specialist (nephrologist, urologist, or interventional radiologist). Indications for diagnostic biopsy include unexplained nephritic or nephrotic... read more . The location of immune complex deposits can help differentiate between types; typically subendothelial and mesangial in type I, intramembranous in type II, and subepithelial in type III. Other tests are also done.
Serum complement profiles are more frequently abnormal in membranoproliferative glomerulonephritis than in other glomerular disorders and provide supportive evidence of the diagnosis (see table Serum Complement Profiles in Membranoproliferative Glomerulonephritis Serum Complement Profiles in Membranoproliferative Glomerulonephritis ). C3 levels are often low. In type I disease, the classic complement pathway is activated and C3 and C4 are decreased. C3 may be decreased more often than C4 at diagnosis and decreases further during follow-up, but eventually normalizes. In type II disease, the alternate complement pathway is activated and C3 is more frequently and severely reduced than in type I while C4 levels are normal. In type III disease, C3 is reduced but C4 is normal. C3 nephritic factor is detectable in 80% of patients with type II and in some patients with type I disease. Terminal complement nephritic factor is detectable in 20% of patients with type I, rarely in patients with type II, and 70% of patients with type III disease.
Serologic tests (eg, for systemic lupus erythematosus Diagnosis Systemic lupus erythematosus is a chronic, multisystem, inflammatory disorder of autoimmune etiology, occurring predominantly in young women. Common manifestations may include arthralgias and... read more , hepatitis B and C virus Serology Acute viral hepatitis is diffuse liver inflammation caused by specific hepatotropic viruses that have diverse modes of transmission and epidemiologies. A nonspecific viral prodrome is followed... read more , and cryoglobulinemia) are warranted to check for secondary causes of type I disease.
Complete blood count (CBC), often obtained in the course of diagnostic evaluation, demonstrates normochromic-normocytic anemia, often out of proportion to the stage of renal insufficiency (possibly because of hemolysis), and thrombocytopenia from platelet consumption.
Prognosis is good if a condition causing secondary membranoproliferative glomerulonephritis is successfully treated. Idiopathic type I membranoproliferative glomerulonephritis often progresses slowly; type II progresses more rapidly. In general, the long-term prognosis is poor. End-stage renal disease Chronic Kidney Disease Chronic kidney disease (CKD) is long-standing, progressive deterioration of renal function. Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia... read more occurs in 50% of patients at 10 years and in 90% at 20 years. Spontaneous remission occurs in < 5% with type II. Type I membranoproliferative glomerulonephritis recurs in 30% of kidney transplantation Kidney Transplantation Kidney transplantation is the most common type of solid organ transplantation. (See also Overview of Transplantation.) The primary indication for kidney transplantation is End-stage renal failure... read more patients; type II recurs in 90% but, despite this high recurrence rate, leads to graft loss only infrequently. Outcome tends to be worse if proteinuria is in the nephrotic range.
Corticosteroids for children with nephrotic-range proteinuria
Dipyridamole and aspirin for adults
Underlying disorders are treated when possible. Specific therapy is probably not indicated for patients with non-nephrotic–range proteinuria, which usually suggests slow progression.
Among children with nephrotic-range proteinuria, treatment with corticosteroids (eg, prednisone 2.5 mg/kg orally once a day on alternate days [maximum 80 mg/day]) for 1 year, followed by tapering to a maintenance dose of 20 mg on alternate days for 3 to 10 years, may stabilize renal function. However, corticosteroid treatment may retard growth and cause hypertension Hypertension Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more .
Among adults, dipyridamole 225 mg orally once a day with aspirin 975 mg orally once a day for 1 year may stabilize renal function at 3 to 5 years, but at 10 years there is no difference from placebo. Studies of antiplatelet therapy yield inconsistent results.
Alternate therapies are sometimes substituted for the usual treatments (eg, corticosteroids could exacerbate underlying hepatitis C Hepatitis C, Chronic Hepatitis C is a common cause of chronic hepatitis. It is often asymptomatic until manifestations of chronic liver disease occur. Diagnosis is confirmed by finding positive anti-HCV and positive... read more ). Alternative therapies include pegylated interferon alfa-2a or pegylated interferon alfa-2b (with addition of ribavirin if creatinine clearance is >50 mL/min) for hepatitis C virus–associated disease and plasma exchange with corticosteroids for concomitant severe cryoglobulinemia or rapidly progressive glomerulonephritis Rapidly Progressive Glomerulonephritis (RPGN) Rapidly progressive glomerulonephritis is acute nephritic syndrome accompanied by microscopic glomerular crescent formation with progression to renal failure within weeks to months. Diagnosis... read more . Angiotensin-converting enzyme (ACE) inhibitors may decrease proteinuria and help control hypertension.
Membranoproliferative glomerulonephritis is a group of immune-mediated disorders with some common histologic features.
Patients most often present with nephrotic syndrome, but they may present with nephritic syndrome.
Confirm the diagnosis with renal biopsy and obtain serum complement profile and serologic tests.
Treat children who have nephrotic range proteinuria with corticosteroids.
Drugs Mentioned In This Article
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