Pediatric Anti-GBM Disease (Goodpasture Syndrome) Treatment & Management

Treatment of anti–glomerular basement membrane (anti-GBM) disease (Goodpasture disease) requires a 2-pronged approach consisting of the removal of the pathogenic antibody and the prevention of new antibody production.

A comprehensive review by Knoll et al stated that patients with anti-GBM disease and end-stage renal disease (ESRD) should be candidates for a renal transplant if they have undetectable anti-GBM titers and are in clinical remission off alkylating agents for at least 6 months. ^[18]

Successful transplantation of 2 pediatric patients with ESRD and anti-GBM disease were recently described; they were transplanted at 9 months and 12 months after presentation, respectively. ^[16] Closely monitor patients by obtaining regular anti-GBM titers, serum creatinine levels, and chest radiographs to decide on the duration of various therapies.

Go to Goodpasture Syndrome for complete information on this topic.

Consultations

Patients with anti-GBM disease can present with renal or pulmonary symptoms and are often critically ill. Therefore, pulmonologists, nephrologists, and critical care specialists are commonly involved in the care of these patients.

Most treatments are aimed at both renal and pulmonary conditions. Effective cooperation and communication with regard to the timing and duration of these therapies is essential.

Transfer

A severely ill patient with anti-GBM disease may need to be transferred if the hospital has insufficient intensive care support.

Extracorporeal membrane oxygenation (ECMO) has been tried in pediatric patients with severe pulmonary involvement that is unresponsive to conventional ventilatory support. Transfer to a tertiary care center may be needed if such circumstances are impending.

For anti–glomerular basement membrane (anti-GBM) antibody removal, literature about adults recommends plasma exchange every day for 14 days or every third day for a month. Each session consists of an exchange volume of 3-4 L and its replacement with albumin or fresh-frozen plasma.

Pediatric patients with anti-GBM disease (Goodpasture disease) have also been given plasma exchange in conjunction with corticosteroids and cyclophosphamide. The pediatric literature supports plasma exchange of a single or 1.5-times plasma volume on a daily basis for at least 5 days, followed by a change to alternate day for an additional 6-7 treatments. Replacement is usually with fresh-frozen plasma or 5% albumin. Anti-GBM titers should be monitored to demonstrate removal. ^{[16, 19]}

Patients must be monitored for leukopenia or thrombocytopenia, as well as regularly assessed for their blood pressure, renal function, and pulmonary function. It is also critical to prevent or treat opportunistic infections.

Other complications of plasma exchange include the following:

• Anaphylactoid reactions, usually when fresh-frozen plasma is used

• Metabolic alkalosis from solutions with high citrate and low chloride, especially when renal function is poor

• Hemorrhage or thrombosis

• Posttransfusion hepatitis

• End-stage renal disease (ESRD)

Opportunistic infections can occur secondary to the patient's immunosuppressed state. Fungal, opportunistic bacterial, and catheter-related infections should be considered in these patients, especially if they are receiving triple therapy with corticosteroids, cyclophosphamide, and plasma exchange.

Although theoretically possible, relapse of anti-GBM disease is relatively uncommon. Recurrent pulmonary hemorrhage associated with infection or cigarette smoking has been reported in adults.

It should be noted that in the only randomized trial of plasma exchange in anti-GBM disease was performed in adults. While only 2 of 8 patients in the plasma exchange group were dialysis dependent versus 6 of 9 in the immunosuppression only group, the authors concluded that renal function and the degree of crescentic involvement on renal biopsy were better predictors of outcome than was the therapeutic intervention selected. ^[20]

Therapy with corticosteroids (eg, prednisone) and cyclophosphamide is aimed at eliminating ongoing antibody synthesis.

Adult patients who present with a serum creatinine level greater than 8 mg/dL have poor renal outcomes. Therefore, seriously consider whether to use this aggressive treatment regimen in patients presenting with limited pulmonary disease and marked renal impairment (serum creatinine >8 mg/dL). There does not appear to be a serum creatinine value that is predictive of renal outcome, as Williamson et al have reported a teenager with a creatinine level of 13.9 mg/dL and 100% crescents on renal biopsy at presentation who was treated with prednisone, cyclophosphamide, plasmapheresis, and peritoneal dialysis. One year later this patient was off dialysis with a creatinine value of 2.1 mg/dL. ^[16]

Isolated reports describe the use of rituximab, an anti-CD20 monoclonal antibody, in autoimmune disorders aimed at targeting B lymphocytes and their antibody production.

Arzoo et al reported the use of rituximab markedly improved the condition of a 73-year-old woman whose recurrent anti-GBM disease was refractory to treatment with steroids, plasmapheresis, and cyclophosphamide. ^[21] The marked improvement occurred after the second of 6 weekly prescribed doses of rituximab at 375 mg/m²/dose. This coincided with the disappearance of circulating anti-GBM antibodies. ^[21]

In pediatric patients, plasma exchange has been administered in conjunction with corticosteroids and cyclophosphamide. The duration of the immunosuppressive treatment varies but is typically 6 months for steroids and 3 months for cyclophosphamide. Rituximab has been used in pediatric autoimmune disorders, but no reports suggest its use for anti-GBM disease in the pediatric age group. This agent is a potent immunosuppressive and needs to be used with caution, weighing the risks and benefits (see Medication).

Sodium restriction

Pediatric patients with anti–glomerular basement membrane (anti-GBM) disease (Goodpasture disease) who are taking corticosteroids are restricted to a sodium intake of 3 mEq/kg/d. The daily total should not exceed 2 g. On the basis of the molecular weight of sodium, 1 mEq is equal to 23 mg.

Fluid restriction

The recommended fluid intake largely depends on the patient's renal function and whether the patient is taking cyclophosphamide.

Patients with a good urine output and a stable blood pressure do not require fluid restriction. Moreover, if the same patients are taking cyclophosphamide, liberal fluid intake is encouraged to promote urine output and to prevent the risk of hemorrhagic cystitis.

Conversely, administration of cyclophosphamide to patients with oliguric renal failure can be challenging. Caregivers must weigh the benefits of this therapy against the risks of hemorrhagic cystitis, with a potential increased risk for bladder cancer in the future. One consideration in this setting would be intravenous cyclophosphamide (dose adjusted for renal dysfunction) accompanied by MESNA; in addition, instilling a urinary catheter for bladder irrigation can be considered if oligoanuria exists.

Activity

Once discharged from the hospital, recovering patients can resume their usual activities unless they have undergone renal biopsy. These patients should avoid running and jumping for 2 weeks, and they are restricted from contact sports for 1 month after the date of biopsy.

If significant anemia is present, the patient's tendency to become fatigued is likely to restrict his or her usual activity level.

Continued inpatient treatment is necessary for the following potential complications of anti–glomerular basement membrane (anti-GBM) disease (Goodpasture disease):

• Relapse of anti-GBM disease (ie, pulmonary hemorrhage, deterioration of renal function)

• Need to initiate dialysis

• Complications related to dialysis

• Need for kidney transplantation

• Opportunistic infections

Perform a weekly complete blood cell (CBC) count to monitor for leukopenia or thrombocytopenia while the patient is taking cyclophosphamide.

Outpatient clinic visits may be required to monitor the patient's blood pressure, renal function, and pulmonary function. Pulmonary function and hemorrhage can be monitored with pulmonary function testing and diffusion capacity of the lungs for carbon monoxide (DLCO) measurements.

Patients may receive peritoneal dialysis or hemodialysis. Peritoneal dialysis can be performed daily at home, whereas hemodialysis is typically performed 3 times per week at a dialysis center.

Pediatric patients needing plasma exchange may receive exchange volumes of 0.5-3.8 L, depending on their size. The treatments are typically given daily for approximately 10 days or until the anti-GBM titer has decreased to normal levels.