eMedicine Specialties > Nephrology > Glomerular Diseases
Glomerulonephritis, Membranous: Treatment & Medication
Updated: Dec 16, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
Search for an underlying cause. Successful treatment of the underlying cause may be curative in secondary forms.
- A low-salt diet is key to reducing anasarca. Protein restrictions may or may not be useful in reducing the rate of progression of chronic renal failure.
- Diuretics help control edema. Loop diuretics are used most often.
- NSAIDs help to decrease the proteinuria. These have been largely supplanted by angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs).
- ACE inhibitors decrease proteinuria and control hypertension; use ARBs for patients intolerant of ACE inhibitors.
- Hepatic 3-methylglutaryl coenzyme A reductase inhibitors help treat hypercholesterolemia.
- Routine anticoagulation is controversial. However, the risk of renal vein thrombosis and other deep vein thromboses is significant, and the clinician must be vigilant in monitoring for signs of venous thrombosis. Once found, anticoagulation is generally continued indefinitely.
- In hepatitis-associated membranous nephropathy, antivirals may be useful.
- Treat hypertension aggressively.
- Do not treat patients with asymptomatic nonnephrotic proteinuria with immunosuppressives. Patients who are asymptomatic and nephrotic may undergo remission, particularly if they have normal renal function and an early lesion. They may also be observed.
- Therapy with immunosuppressive agents is indicated in those patients who have the following:
- Increased creatinine level at presentation
- Progressive disease
- Severe symptomatic nephrotic syndrome
- Persistent nephrotic syndrome
- Thromboembolism
- Persistent nephrotic syndrome, male sex, and age older than 50 years
- Increased IgG excretion, HLA-DR3+/B8+, white race, and elevation of urinary excretion of complement activation products
- Tubulointerstitial changes or focal sclerosis
Surgical Care
Transplantation is indicated if the patient progresses to ESRD. Some risk of recurrence in the allograft is recognized.
Diet
- Institute a low-salt diet.
- Protein restrictions may or may not be useful.
Activity
- Activity can be performed as tolerated.
Medication
Corticosteroids alone are ineffective in the treatment of membranous nephropathy. Additionally, cyclophosphamide and chlorambucil should be reserved for patients who exhibit clinical features, such as severe or prolonged nephrosis, renal insufficiency, or hypertension.
Alternating monthly treatment with a combination of chlorambucil and steroids for 6 months has also been tried, with some success, especially in patients with a creatinine level of less than 1.7 mg/dL. A 20-year follow-up of these patients showed complete remission in 9 out of 15 patients and partial remission in 4 out of 15 patients; 2 out of 15 patients did not respond. The 10-year survival rate of the treated patients was 100%, whereas that of the untreated patients was 40%.4 Cyclophosphamide can be used as an alternative, and cyclosporine is indicated in those patients in whom the above cannot be used or in patients with a high risk of progression.
One review failed to show any long-term effects of immunosuppressive treatment on patient and/or renal survival. An increased number of discontinuations were because of adverse events in the immunosuppressive treatment groups. Within the class of alkylating agents, weak evidence supports the efficacy of cyclophosphamide as compared to chlorambucil. On the other hand, cyclophosphamide had fewer adverse effects leading to patient withdrawal than chlorambucil.
Recently, mycophenolate mofetil has been used with some success. A comparison of mycophenolate mofetil with cyclophosphamide showed decreased proteinuria and improved renal function in most patients, but mycophenolate mofetil did not appear as effective as or better tolerated than cyclophosphamide.5
Tacrolimus has also been used with some success. Monoclonal antibodies against the B cell surface antigen CD20 have been used to explore whether specific inhibition of B cells may help improve the outcome of idiopathic membranous nephropathy and may avoid the adverse effects of steroids and immunosuppressants. Promising results have recently been obtained with rituximab, a monoclonal antibody against the CD20 antigen of B lymphocytes that is able to deplete these cells.6
Titrating rituximab to circulating CD20 B cells may improve safety by avoiding hypersensitivity; it also may limit the costs of treatment while achieving similar results.7 However, it has not been possible to precisely predict which patients will respond to rituximab.8
In secondary membranous nephropathy associated with hepatitis B, in addition to interferon, lamivudine monotherapy may induce and maintain complete remission.9
Histology findings in idiopathic membranous nephropathy have been associated with the risk of renal failure, but whether they are independent of the clinical variables at the time of biopsy, predict rate of progression, or should guide therapy is uncertain. Although these histologic features were associated with a reduced renal survival rate, they did not predict this outcome independently of the baseline clinical variables nor did they correlate with the rate of decline in function.10
Diuretics
Used to control volume overload.
Furosemide (Lasix)
Has a potent diuretic effect because it blocks sodium reabsorption in the thick ascending loop of Henle.
Adult
20-80 mg/d PO; not to exceed 600 mg/d
Pediatric
1-2 mg/kg/dose PO; not to exceed 6 mg/kg/dose q6h
Alcohol and CNS depressants may exacerbate orthostatic hypotension; effects are antagonized by indomethacin; may alter salicylate and lithium levels; hearing loss may occur with concurrent administration of aminoglycoside
Potentiates therapeutic effect of other antihypertensives; avoid ethacrynic acid because of the possibility for ototoxicity; antagonizes effect of tubocurarine and potentiates the action of succinylcholine
Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in renal or hepatic dysfunction, diabetes, and gout; monitor electrolytes and renal profile; potassium replacement may be needed
Adverse effects may include GI upset, dizziness, vertigo, paresthesias, orthostatic hypotension, hyperglycemia, jaundice, hyperuricemia, rash, photosensitivity, tinnitus, hearing loss, interstitial nephritis, and blood dyscrasias
Hepatic 3-methylglutaryl coenzyme A reductase inhibitors
Decrease the increased cholesterol associated with nephrotic syndrome.
Simvastatin (Zocor)
Decreases intracellular cholesterol pools and increases LDL receptors, which causes a decrease in LDL-C.
Adult
10-40 mg/d PO
Pediatric
Not established
Rifampin and nicotinic acid may decrease effects; clofibrate, itraconazole, erythromycin, cyclosporine, and niacin increase toxicity; coadministration with niacin or erythromycin associated with rhabdomyolysis; increases toxicity of anticoagulants and levothyroxine
Documented hypersensitivity; active liver disease; unexplained elevation of liver enzymes
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Monitor liver function and CK; suspend if a predisposition to development of renal failure secondary to rhabdomyolysis develops
Adverse effects include elevated serum transaminase levels, GI upset, headache, rash, pruritus, myalgia, dizziness, blurred vision, and rhabdomyolysis
Atorvastatin (Lipitor)
Inhibits 3-hydroxy-3-methylglutaryl coenzyme A, which, in turn, inhibits cholesterol synthesis and increases cholesterol metabolism.
Adult
10 mg PO qd; titrate to a maximum of 80 mg/d prn
Pediatric
Not established
Toxicity increases when coadministered with triazole antifungals, CNS depressants, macrolide antibiotics, and mibefradil
Documented hypersensitivity; significant hepatic impairment
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Do not exceed daily dose; caution in patients receiving drugs which prolong QRS or Q-T interval
Corticosteroids
Induce remission of proteinuria.
Prednisone (Deltasone, Meticorten, Orasone, Sterapred)
Exerts an anti-inflammatory effect via the inhibition of inflammatory mediator gene transcription.
Adult
1 mg/kg/d PO on alternate days from cyclophosphamide
Pediatric
2 mg/kg/d PO on alternate days from cyclophosphamide
Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Documented hypersensitivity; viral infection, peptic ulcer disease, hepatic dysfunction, connective tissue infections, and fungal or tubercular skin infections; GI disease
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Tuberculosis, ocular herpes simplex, peptic ulcer, hypertension, osteoporosis, and diabetes
Supplement with additional steroids in physiologic stress
Avoid abrupt cessation; alternate-day, intermittent, or single-day doses at 8 am minimize adrenal suppression; monitor weight, growth, and fluid and electrolyte balance
Adverse effects include HPA axis suppression, masking of infection, glaucoma, cataracts, secondary infections, hypokalemia, hypocalcemia, hypernatremia, hypertension, psychic disorders, myopathy, osteoporosis, peptic ulcer, dermal atrophy, increased intracranial pressure, and carbohydrate intolerance
Methylprednisolone (Adlone, Medrol, Solu-Medrol)
Exerts an anti-inflammatory effect via inhibition of inflammatory mediator gene transcription.
Adult
1 mg/kg/d PO on alternate days from cyclophosphamide
Pediatric
2 mg/kg/d PO on alternate days from cyclophosphamide
Coadministration with digoxin may increase digitalis toxicity secondary to hypokalemia; estrogens may increase levels; phenobarbital, phenytoin, and rifampin may decrease levels (adjust dose); monitor patients for hypokalemia when taking concurrently with diuretics
Documented hypersensitivity; viral, fungal, or tubercular skin infections
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Tuberculosis, ocular herpes simplex, peptic ulcer, hypertension, osteoporosis, and diabetes
Supplement with additional steroids in physiologic stress
Avoid abrupt cessation; alternate-day, intermittent, or single-day doses at 8 am minimize adrenal suppression; monitor weight, growth, and fluid and electrolyte balance
Adverse effects include HPA axis suppression, masking of infection, glaucoma, cataracts, secondary infections, hypokalemia, hypocalcemia, hypernatremia, hypertension, psychic disorders, myopathy, osteoporosis, peptic ulcer, dermal atrophy, increased intracranial pressure, and carbohydrate intolerance
Cyclophosphamide (Cytoxan, Neosar)
Used for remission of nephrotic syndrome. Interferes with normal function of DNA by alkylation and cross-linking the strands of DNA and by possible protein modification.
Adult
1.5 mg/kg/d PO; given on alternate day from prednisone
Pediatric
2.5-3 mg/kg/d PO (not to exceed 90 d) given on alternate day from prednisone
Allopurinol may increase risk of bleeding or infection and enhance myelosuppressive effects; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones
Chloramphenicol may increase half-life while decreasing metabolite concentrations; may increase effect of anticoagulants; coadministration with high doses of phenobarbital may increase rate of metabolism and leukopenic activity of cyclophosphamide; thiazide diuretics may prolong cyclophosphamide-induced leukopenia and neuromuscular blockade by inhibiting cholinesterase activity
Documented hypersensitivity; severely depressed bone marrow function, breastfeeding
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Regularly examine hematologic profile (particularly neutrophils and platelets) to monitor for hematopoietic suppression; regularly examine urine for RBCs, which may precede hemorrhagic cystitis; caution in hepatic or renal impairment, leukopenia, and thrombocytopenia; adverse effects include CHF, secondary malignancies, leukopenia, renal tubular necrosis, poor wound healing, anorexia, nausea, vomiting, alopecia, thrombocytopenia, anemia, hemorrhagic and nonhemorrhagic cystitis, gonadal suppression, interstitial pulmonary fibrosis, pigmentation changes, dermatitis, and jaundice
Chlorambucil (Leukeran)
For remission of proteinuria; given with prednisone (0.5 mg/kg/d) every other month. Steroids are given as 1 g methylprednisolone IV for 3 d. Interferes with DNA replication and RNA transcription by alkylation and cross-linking the strands of DNA
Adult
0.2 mg/kg/d PO for 5-15 wk
Pediatric
0.1-0.2 mg/kg/d PO for 5-15 wk
Myelosuppressives and radiotherapy potentiate antineoplastic effect; antigout agents are antagonized
Documented hypersensitivity; previous resistance to medication
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Compromised bone marrow function or seizure disorder; monitor blood counts weekly; adverse effects include bone marrow suppression, leukemia, seizures, hyperuricemia, oral ulcerations, fever, rash, urticaria, azoospermia, amenorrhea, sterility in prepubertal and pubertal males, bronchopulmonary dysplasia, and pulmonary fibrosis; impaired immune response to vaccines possible (infection after administration of live vaccines may occur)
Immunosuppressant agents
For remission of nephrotic syndrome.
Cyclosporine A (Sandimmune)
Inhibits production and release of IL-2, leading to inhibition of IL-2–mediated activation of T lymphocytes.
Adult
4-6 mg/kg/d PO in 2 divided doses to keep trough level at 120-200 ng/mL
Pediatric
Not established
Carbamazepine, phenytoin, isoniazid, rifampin, and phenobarbital may decrease concentrations; azithromycin, itraconazole, nicardipine, ketoconazole, fluconazole, erythromycin, verapamil, grapefruit juice, diltiazem, aminoglycosides, acyclovir, amphotericin B, and clarithromycin may increase toxicity; acute renal failure, rhabdomyolysis, myositis, and myalgias increase when taken concurrently with lovastatin
Documented hypersensitivity; uncontrolled hypertension or malignancies; do not administer concomitantly with PUVA or UVB radiation in psoriasis because may increase risk of cancer
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Nephrotoxic; can raise blood pressure; caution in glaucoma, Tourette syndrome, infections, and lymphoma; use drug levels to monitor dose; airway and other supportive measures should be available for the treatment of anaphylaxis when giving an IV dose
Adverse effects include hypertension, hirsutism, gingival hypertrophy, hypomagnesemia, hyperkalemia, tremor, seizure, headache, nephrotoxicity, nausea, vomiting, leg cramps, hepatotoxicity, hyperlipidemia, glucose intolerance, increased immunologic and infectious complications, hyperuricemia, and increased incidence of thromboembolic events
Angiotensin-converting enzyme inhibitors
Control blood pressure and proteinuria.
Lisinopril (Zestril, Prinivil)
Inhibition of ACE leads to decreased plasma angiotensin II, which, in turn, leads to decreased vasopressor activity and decreased aldosterone secretion. ACE inhibitors minimize secondary intraglomerular hypertension and hypertrophy, leading to decreased proteinuria in idiopathic membranous nephropathy.
Adult
10-40 mg PO qd
Pediatric
0.5 mg/kg/dose PO in 2-4 divided doses, not to exceed 6 mg/kg/d
May increase digoxin, lithium, and allopurinol levels; probenecid may increase levels; coadministration with diuretics increases hypotensive effects; hypotensive effects may be enhanced when given concurrently with diuretics and NSAIDs
Documented hypersensitivity; ACE-associated angioedema
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in aortic stenosis; monitor renal function and WBC count; monitor for hyperkalemia
Adverse effects include hypotension, headache, dysgeusia, rash, pruritus, dizziness, fatigue, cough, proteinuria, GI upset, hyperkalemia, hyponatremia, tachycardia, dry mouth, angioedema, jaundice, somnolence, sweating, sinusitis, impotence, and agranulocytosis
Enalapril (Vasotec)
Competitive inhibitor of ACE. Reduces angiotensin II levels, decreasing aldosterone secretion.
Adult
2.5-5 mg/d PO (increase prn)
Dosing range: 10-40 mg/d PO in 1-2 divided doses; alternatively, 1.25 mg/dose IV over 5 min q6h
Pediatric
Not established
NSAIDs may reduce hypotensive effects; ACE inhibitors may increase digoxin, lithium, and allopurinol levels; rifampin decreases levels; probenecid may increase levels; hypotensive effects of ACE inhibitors may be enhanced when given concurrently with diuretics
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in renal impairment, valvular stenosis, or severe congestive heart failure
Nonsteroidal anti-inflammatory drugs
Used to decrease proteinuria.
Ibuprofen (Motrin, Ibuprin)
Exerts its effects by inhibiting both constitutive and inducible isoforms of cyclooxygenase, which produces a mild-to-moderate anti-inflammatory and analgesic effect. NSAIDs decrease intraglomerular pressure and decrease proteinuria.
Adult
400 mg PO q4-6h, 600 mg q6h, or 800 mg q8h while symptoms persist; not to exceed 3.2 g/d
Pediatric
20-70 mg/kg/d PO divided tid/qid; start at lower end of dosing range and titrate; not to exceed 2.4 g/d
Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; monitor PT closely (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently
Documented hypersensitivity; peptic ulcer disease, recent GI bleeding or perforation, renal insufficiency, or high risk of bleeding
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Category D in third trimester of pregnancy; caution in congestive heart failure, hypertension, and decreased renal and hepatic function; caution in anticoagulation abnormalities or during anticoagulant therapy
Naproxen (Anaprox, Naprelan, Naprosyn)
For relief of mild to moderate pain; inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which is responsible for prostaglandin synthesis.
Adult
250-500 mg PO bid; may increase to 1.5 g/d for limited periods
Pediatric
<2 years: Not established
>2 years: 2.5 mg/kg/dose PO; not to exceed 10 mg/kg/d
Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; monitor PT closely (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently
Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Category D in third trimester of pregnancy; acute renal insufficiency, interstitial nephritis, hyperkalemia, hyponatremia, and renal papillary necrosis may occur; patients with preexisting renal disease or compromised renal perfusion risk acute renal failure; leukopenia occurs rarely, is transient, and usually returns to normal during therapy; persistent leukopenia, granulocytopenia, or thrombocytopenia warrants further evaluation and may require discontinuation of drug
Ketoprofen (Actron, Orudis, Oruvail)
For relief of mild to moderate pain and inflammation.
Small doses are initially indicated in small and elderly patients and in those with renal or liver disease. Doses >75 mg do not increase therapeutic effects. Administer high doses with caution and closely observe patient for response.
Adult
25-50 mg PO q6-8h prn; not to exceed 300 mg/d
Pediatric
<3 months: Not established
3 months to 12 years: 0.1-1 mg/kg PO q6-8h
>12 years: Administer as in adults
Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; monitor PT closely (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Category D in third trimester of pregnancy; caution in congestive heart failure, hypertension, and decreased renal and hepatic function; caution in anticoagulation abnormalities or during anticoagulant therapy
More on Glomerulonephritis, Membranous |
| Overview: Glomerulonephritis, Membranous |
| Differential Diagnoses & Workup: Glomerulonephritis, Membranous |
 Treatment & Medication: Glomerulonephritis, Membranous |
| Follow-up: Glomerulonephritis, Membranous |
| References |
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References
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Further Reading
Keywords
membranous glomerulonephritis, membranous nephropathy, nephrotic syndrome
