eMedicine Specialties > Nephrology > Glomerular Diseases
Goodpasture Syndrome: Treatment & Medication
Updated: Oct 13, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
In the appropriate clinical setting (ie, alveolar hemorrhage and urinary findings suggestive of an acute glomerulonephritis), the detection of circulating anti-GBM antibodies allows the clinician to make a firm diagnosis of anti-GBM disease. This obviates the need for lung or kidney biopsy. When the diagnosis remains in doubt, renal biopsy is the best method for detecting anti-GBM antibodies in tissues. The biopsy tissue must be processed not only for light microscopy but also for immunofluorescence and electron microscopy. Renal biopsy provides a significantly higher yield compared to lung biopsy.
- The 3 principles of therapy are (1) to rapidly remove circulating antibody, primarily by plasmapheresis; (2) to stop further production of antibodies using immunosuppression with medications; and (3) to remove offending agents that may have initiated the antibody production.
- Before the availability of current therapy, the mortality rate exceeded 90%, with a mean survival time of less than 4 months. Currently, with the combination of plasmapheresis, corticosteroids, and cyclophosphamide, the mortality rate has been reduced to less than 20%.
- Based on published case series and one randomized trial, plasmapheresis has been shown to be beneficial in the treatment of Goodpasture syndrome by removal of anti-GBM antibodies. Plasmapheresis is generally instituted after the diagnosis of Goodpasture syndrome is established either by renal biopsy or by detection of anti-GBM antibodies. However, when a patient presents in a life-threatening situation secondary to pulmonary hemorrhage, plasmapheresis may be initiated if the diagnosis appears very likely, even though the confirmation is not available immediately. The extent and duration of plasmapheresis is not known, but 4 plasma exchanges (1 L each) daily or every other day are performed. The plasmapheresis is continued for 2-3 weeks or until the patient's clinical course has improved and serum anti-GBM antibodies are not detected.
- Immunosuppressive therapy:
- Immunosuppressive therapy is required to inhibit antibody production and rebound hypersynthesis, which may occur following discontinuation of plasma exchange.
- Cyclophosphamide at 2 mg/kg orally, adjusted to maintain a white blood cell count of approximately 5000, is instituted and continued for 6 months.
- Corticosteroids (eg, prednisone at 1-1.5 mg/kg) are also initiated and gradually tapered over 6 months following clinical remission.
- Treatment of acute life-threatening alveolar hemorrhage in patients with Goodpasture syndrome is with pulse methylprednisolone at 1 g/d for 3 days, followed by a gradual corticosteroid taper. Intravenous cyclophosphamide is begun concomitantly at 1 g/m2 and repeated 3-4 weeks later, depending on the recovery of bone marrow.
- The duration of immunosuppressive therapy is not well established. Treatment is continued for 3-6 months, provided a sustained remission has been achieved and anti-GBM antibodies have disappeared.
- Relapse:
- The circulating antibodies clear within 8 weeks, but an early relapse (ie, within first 2 mo) may occur when circulating antibodies are still present. This typically manifests as alveolar hemorrhage.
- The risk factors for relapse include infection, volume overload, and cigarette smoking.
- Late relapse has been documented only rarely.
Surgical Care
Renal transplantation has been used for ESRD secondary to Goodpasture syndrome. The incidence of linear deposits of IgG along glomeruli of the renal allograft is high, but this development does not cause histologic or functional damage to the transplanted kidney. Most transplant centers prefer to wait 6-12 months after serologic evidence indicates that anti-GBM antibodies have cleared.
Consultations
- Renal consultation: Consult a nephrologist for evaluation of the patient in regard to the differential diagnosis of the renal disease, indication for renal biopsy, requirement for hemodialysis or plasmapheresis, and therapeutic input.
- Pulmonary consultation: Consult a pulmonologist for patients with significant hemoptysis or respiratory compromise because these patients may deteriorate very rapidly and require bronchoscopy and/or intubation.
- Vascular surgery: A consultation with a vascular surgeon may be required for placement of vascular access for hemodialysis or plasmapheresis.
Diet
Renal diet is instituted.
Medication
The goals of pharmacotherapy are to reduce morbidity and to prevent complications.
Immunosuppressive agents
The treatment of choice is a combination of plasmapheresis to remove the circulating anti-GBM antibodies and immunosuppression with glucocorticoids and cytotoxic agents to inhibit further autoantibody formation. For induction therapy, prednisone and cyclophosphamide are initiated. Prednisone is tapered over 2-3 months, and cyclophosphamide is continued for as long 6 months (depending on the status of anti-GBM antibodies). Azathioprine may be used for patients who do not tolerate cyclophosphamide therapy.
Prednisone (Sterapred)
Used as an immunosuppressant in the treatment of autoimmune disorders. By reversing increased capillary permeability and suppressing PMN activity, may reduce inflammation.
For severe or rapidly progressing disease, methylprednisolone at a dose of 250 mg q6h should be administered. Once the patient is stabilized, continue PO therapy with prednisone.
Adult
1-1.5 mg/kg PO qd for 4-6 wk; not to exceed 100 mg/d; taper gradually over another 6 wk and discontinue
Pediatric
Not established
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; increased risk of peptic ulcer disease if taking aspirin or NSAIDs
Documented hypersensitivity; viral infections; peptic ulcer disease; hepatic dysfunction; connective tissue infections; 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
Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use
Methylprednisolone (Solu-Medrol)
DOC for severe disease. Should be started concomitantly with plasmapheresis. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.
Adult
500 mg to 1 g IV for 3 d qd or bid/qid followed by gradual reduction to lowest level that maintains clinical response
Pediatric
0.5-1.7 mg/kg/d or 5-25 mg/m2/d PO/IV/IM divided q6-12h
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 diuretics concurrently
Documented hypersensitivity; viral, fungal, or tubercular skin infections
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
Hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications of glucocorticoid use; caution in patients with hypertension, congestive heart failure, ulcerative colitis, or thromboembolic disease
Cyclophosphamide (Cytoxan)
Chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells. Has anti-inflammatory effect.
Treat for 6-12 mo (the time usually required for cessation of anti-GBM antibody formation).
Adult
2 mg/kg IV initially; not to exceed 200 mg/d; goal is to reduce and maintain WBC count at 4000-7000/mm3
Pediatric
Not established
Allopurinol may increase the 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 of barbiturates, phenytoin, or chloral hydrate may increase rate of metabolism and leukopenic activity; thiazide diuretics may prolong cyclophosphamide-induced leukopenia and neuromuscular blockade by inhibiting cholinesterase activity
Documented hypersensitivity; severely depressed bone marrow function
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 impaired renal or hepatic function, leukopenia, or thrombocytopenia
Azathioprine (Imuran)
Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells, which results in lower autoimmune activity.
Treat for 6-12 mo (the time usually required for cessation of anti-GBM antibody formation).
Adult
2 mg/kg/d PO as single dose; not to exceed 200 mg/d
Pediatric
Not established
Toxicity increases with allopurinol; concurrent use with ACE inhibitors may induce severe leukopenia; may increase levels of methotrexate metabolites and decrease effects of anticoagulants, neuromuscular blockers, and cyclosporine
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
GI disturbances (eg, nausea, vomiting, diarrhea, abdominal pain, pancreatitis) may occur; adverse effects include leukopenia, anemia, thrombocytopenia, hepatotoxicity, and increased risk of neoplasm; caution with liver disease and renal impairment
Antibiotics
Patients receiving immunosuppressive therapy should also receive prophylaxis against Pneumocystis pneumonia.
Trimethoprim and sulfamethoxazole (Septra, Bactrim DS)
Inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid, inhibiting folic acid synthesis. Results in inhibition of bacterial growth. Antibacterial activity of TMP-SMZ includes common urinary tract pathogens, except Pseudomonas aeruginosa.
Each DS tab contains 160 mg TMP and 800 mg SMZ.
Adult
1 DS tab/d PO 3 times/wk or qod
Pediatric
<2 months: Do not administer
>2 months: 8 mg TMP/kg/d PO divided bid
May increase PT of warfarin, monitor coagulation tests and adjust dose as required; increased serum levels of both dapsone and TMP may occur when both medications are administered concomitantly; in elderly patients, incidence of thrombocytopenic purpura may increase when used concurrently with diuretics; the hepatic clearance of phenytoin may be decreased and the half-life may be prolonged; sulfonamides can displace MTX from plasma protein binding sites, thus increasing free MTX concentrations, which may potentiate methotrexate effects in bone marrow depression; hypoglycemic response of sulfonylureas may increase with coadministration of both medications; may decrease renal clearance of zidovudine, causing increase in zidovudine levels
Documented hypersensitivity; megaloblastic anemia caused by a folate deficiency
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
Discontinue at first appearance of skin rash or any sign of adverse reaction; obtain CBC counts frequently (if a significant reduction in the count of any formed blood element is noted, discontinue therapy); goiter production, diuresis, and hypoglycemia have occurred; high IV doses or prolonged infusions may cause bone marrow depression manifesting as thrombocytopenia, leukopenia, or megaloblastic anemia; caution in patients with possible folate deficiency, such as those with chronic alcoholism, patients who are elderly, those receiving anticonvulsant therapy, or those with malabsorption syndrome; hemolysis may occur in patients with a G-6-PD deficiency; if signs of bone marrow depression occur, administer leucovorin as needed to restore normal hematopoiesis (leucovorin 5-15 mg/d PO has been recommended); due to unique immune dysfunction, patients with AIDS may not tolerate or respond to TMP-SMZ; caution in patients with renal or hepatic impairment; maintain adequate fluid intake to prevent crystalluria and
stone formation; perform urinalyses and renal function tests during therapy
More on Goodpasture Syndrome |
| Overview: Goodpasture Syndrome |
| Differential Diagnoses & Workup: Goodpasture Syndrome |
 Treatment & Medication: Goodpasture Syndrome |
| Follow-up: Goodpasture Syndrome |
| Multimedia: Goodpasture Syndrome |
| References |
| Further Reading |
| « Previous Page | Next Page » |
References
Zhao J, Cui Z, Yang R, et al. Anti-glomerular basement membrane autoantibodies against different target antigens are associated with disease severity. Kidney Int. Sep 9 2009;[Medline].
Yang R, Cui Z, Zhao J, et al. The role of HLA-DRB1 alleles on susceptibility of Chinese patients with anti-GBM disease. Clin Immunol. Aug 3 2009;[Medline].
Yang R, Hellmark T, Zhao J, et al. Levels of epitope-specific autoantibodies correlate with renal damage in anti-GBM disease. Nephrol Dial Transplant. Jun 2009;24(6):1838-44. [Medline].
Zhao J, Yan Y, Cui Z, et al. The immunoglobulin G subclass distribution of anti-GBM autoantibodies against rHalpha3(IV)NC1 is associated with disease severity. Hum Immunol. Jun 2009;70(6):425-9. [Medline].
Bolton WK. Goodpasture''s syndrome. Kidney Int. Nov 1996;50(5):1753-66. [Medline].
Bombassei GJ, Kaplan AA. The association between hydrocarbon exposure and anti-glomerular basement membrane antibody-mediated disease (Goodpasture''s syndrome). Am J Ind Med. 1992;21(2):141-53. [Medline].
Collard HR, Schwarz MI. Diffuse alveolar hemorrhage. Clin Chest Med. Sep 2004;25(3):583-92, vii.
Donaghy M, Rees AJ. Cigarette smoking and lung haemorrhage in glomerulonephritis caused by autoantibodies to glomerular basement membrane. Lancet. Dec 17 1983;2(8364):1390-3. [Medline].
Frankel SK, Cosgrove GP, Fischer A. Update in the diagnosis and management of pulmonary vasculitis. Chest. Feb 2006;129(2):452-65.
Jara LJ, Vera-Lastra O, Calleja MC. Pulmonary-renal vasculitic disorders: differential diagnosis and management. Curr Rheumatol Rep. Apr 2003;5(2):107-15. [Medline].
Jayne DR, Marshall PD, Jones SJ. Autoantibodies to GBM and neutrophil cytoplasm in rapidly progressive glomerulonephritis. Kidney Int. Mar 1990;37(3):965-70. [Medline].
Kluth DC, Rees AJ. Anti-glomerular basement membrane disease. J Am Soc Nephrol. Nov 1999;10(11):2446-53. [Medline].
Lockwood CM, Rees AJ, Pearson TA. Immunosuppression and plasma-exchange in the treatment of Goodpasture''s syndrome. Lancet. Apr 3 1976;1(7962):711-5. [Medline].
Madore F, Lazarus JM, Brady HR. Therapeutic plasma exchange in renal diseases. J Am Soc Nephrol. Mar 1996;7(3):367-86. [Medline].
Mehler PS, Brunvand MW, Hutt MP. Chronic recurrent Goodpasture''s syndrome. Am J Med. Apr 1987;82(4):833-5. [Medline].
Mokrzycki MH, Kaplan AA. Therapeutic plasma exchange: complications and management. Am J Kidney Dis. Jun 1994;23(6):817-27. [Medline].
Rutgers A, Slot M, van Paassen P. Coexistence of anti-glomerular basement membrane antibodies and myeloperoxidase-ANCAs in crescentic glomerulonephritis. Am J Kidney Dis. Aug 2005;46(2):253-62.
Savage CO, Pusey CD, Bowman C. Antiglomerular basement membrane antibody mediated disease in the British Isles 1980-4. Br Med J (Clin Res Ed). Feb 1 1986;292(6516):301-4. [Medline].
Shah MK, Hugghins SY. Characteristics and outcomes of patients with Goodpasture''s syndrome. South Med J. Dec 2002;95(12):1411-8. [Medline].
Sinico RA, Radice A, Corace C. Anti-glomerular basement membrane antibodies in the diagnosis of Goodpasture syndrome: a comparison of different assays. Nephrol Dial Transplant. Feb 2006;21(2):397-401.
Sutton DM, Nair RC, Rock G. Complications of plasma exchange. Transfusion. Feb 1989;29(2):124-7. [Medline].
Weber MF, Andrassy K, Pullig O. Antineutrophil-cytoplasmic antibodies and antiglomerular basement membrane antibodies in Goodpasture''s syndrome and in Wegener''s granulomatosis. J Am Soc Nephrol. Jan 1992;2(7):1227-34. [Medline].
Further Reading
Clinical trials:
Efficacy of Combined Pentoxifylline and Conventional Immunosuppressive Regimens on Rapidly Progressive Glomerulonephritis
Keywords
Goodpasture syndrome, Goodpasture's syndrome, glomerulonephritis, Goodpasture's disease, type IV collagen, pulmonary hemorrhage, human leukocyte antigen, glomerular basement membrane, , , anti-glomerular basement membrane disease, anti-GBM disease, end-stage renal disease, ESRD, circulating antiglomerular basement membrane antibodies
