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Goodpasture Syndrome: Pathophysiology, Diagnosis, and Management.

Goal:

Discuss the pathophysiology, manifestations, diagnosis, and collaborative management of patients with Goodpasture syndrome.

Objectives:

1. Describe the pathophysiology of Goodpasture syndrome.

2. Identify presenting symptoms, physical examination and laboratory findings, and differential diagnostic findings of patients with Goodpasture syndrome.

3. Summarize the collaborative management of patients with Goodpasture syndrome.

In 1919, Goodpasture described a syndrome characterized by hemoptysis, alveolar hemorrhage and necrosis, and proliferative glomerulonephritis in a patient during an influenza epidemic. Autopsy revealed that the patient had a vasculitis. In succeeding years, many cases were reported in the literature of patients who presented with similar characteristics. In 1958, Stanton and Tange reported a series of young men presenting with pulmonary hemorrhage and glomerulonephritis. They named the syndrome after Goodpasture because of his initial observations (Ball & Young, 1998).

Goodpasture syndrome is infrequent, with an incidence of approximately 0.1 cases per million population (Bolton, 1996). Often Goodpasture syndrome is referred to as young male disease; however, this is incorrect. Gender distribution is approximately equal, and the age at presentation can range from the first to the ninth decade (Bolton, 1996). Goodpasture syndrome has a bimodal age distribution with a greater number of individuals presenting at about age 30, and another at about age 60 (Bolton, 1996). The disease is more frequent in Whites than in African Americans, and even more frequent in other groups such as the Maoris of New Zealand (Bolton, 1996). Goodpasture syndrome can occur year round, but a greater number of cases are diagnosed during spring and summer. Some localized outbreaks have been associated with infection.

The reaction of autoantibodies with glomerular and alveolar basement membranes seems to be a mediating factor in both pulmonary and renal manifestations (Couser, 1988). If treated, pulmonary complications usually resolve and do not have much of an impact on long-term pulmonary function. However, in approximately 70% of cases, the glomerulonephritis leads to chronic renal failure and end stage renal disease (ESRD). Pathophysiology, diagnostic studies, complications, and management are discussed in this article.

Pathophysiology

Goodpasture syndrome is characterized by a triad of findings; antiglomerular basement membrane (GBM) antibodies, rapidly progressive glomerulonephritis (RPGN), and pulmonary hemorrhage. Anti-GBM antibodies attack one of six genetically determined components of basement membrane collagen. A study by Neilson and colleagues (1993) suggested that the target antigen in Goodpasture syndrome is the alpha-3 (IV) collagen chain. This target antigen is found primarily on the inner aspect of the lamina densa, which is the middle layer of the glomerular and alveolar basement membranes, that serves as part of the support structure (Ball & Young, 1998). This support structure can be thought of as the building block, which is composed of three alpha subunits of collagen forming a triple helix (Ball & Young, 1998). This triple helix is made of two alpha 1 chains and one alpha 2 chain. Basement membranes, composed of type IV collagen, laminin, proteoglycans, entactin and other proteins, form an anatomical barrier where cells meet connective tissue (Hellmark, Segelmark, & Wieslander, 1997).

The GBM is in constant contact with blood by way of fenestrations in the glomerular capillaries, which allow access for circulating antibodies to bind to the basement membrane. This binding activates the complement cascade, which causes polymorphonuclear leukocytes (i.e., neutrophils, basophils, and eosinophils) antigen and monocytes to infiltrate the glomerulus (Brenner & Rector, 1996). Fibrinogen leaks into Bowman space and is broken down into fibrin by prothrombinase, which is associated with activated monocytes. These monocytes generate crescents in the glomerulus. Also, interleukin-1 may attract fibroblasts from renal interstitium, which enhance the crescent formation (Brenner & Rector, 1996).

Alveolar capillaries do not have fenestrations, thus the alveolar endothelium acts as a barrier to the antibasement membrane antibodies. The etiology of lung involvement is unclear. Reports indicate that deposition of antibasement membrane antibodies on alveolar basement membrane is related to an additional lung injury that increases alveolar-capillary permeability (Ball & Young, 1998). These lung injuries may include increased pulmonary capillary hydrostatic pressure, high concentrations of inspired oxygen, bacteremia, endotoxemia, hydrocarbons, upper respiratory infections, volume overload, and smoking (Ball & Young, 1998). Smoking is the most frequent underlying pulmonary compromise because it causes an inflammatory process in the lungs that results in release of cytokines, such as interleukin-2 and interferon-alpha, which cause an increase in capillary permeability (Queluz, Pawlowski, & Brunda, 1990). In Donaghy and Rees' (1983) study, 84% of the 47 patients with anti-GBM disease had lung hemorrhage. All patients who smoked developed alveolar hemorrhage. However, 2 out of 10 nonsmokers developed lung hemorrhage that was associated with volume overload and exposure to volatile hydrocarbons.

Although many agents are associated with Goodpasture syndrome, there is strong evidence that genetics also is an important factor. Specific human leukocyte antigens (HLA), inherited glycoproteins expressed on all nucleated cells, have been associated with Goodpasture syndrome. Compared to control populations, patients with Goodpasture syndrome have an increased rate of occurrence of HLA-DR2. HLA-DR2 can be specified into DRw15 and DRw16; Goodpasture syndrome is related to DRw15 (Ball & Young, 1998). Recent studies conclude that an immune response against the Goodpasture antigen depends on the above plus the way in which fragments of the antigen are handled by antigen processing cells such as B lymphocytes, monocytes, macrophages, and dendritic cells (Ball & Young, 1998). The role of these antigens is unclear, but these genetic findings may have a direct or an indirect role in the pathogenesis of Goodpasture syndrome (Ball & Young, 1998).

Diagnosis

Diagnosis of Goodpasture syndrome requires data collected from history, physical examination, and laboratory studies. Initial symptoms are usually nonspecific, such as weakness and fatigue, or they may be related to pulmonary involvement (Netzer, Mertel, & Weber, 1998). Pulmonary alterations vary from mild to moderate lung hemorrhage, manifested as blood-streaked sputum, to massive, fatal pulmonary hemorrhage. Patients often will complain of shortness of breath and cough, but usually not chest pain or pleurisy as occur with pulmonary embolism (Bolton, 1996). Most patients initially present with hematuria, proteinuria, elevated serum creatinine, and possibly oliguria, indicative of progressive renal insufficiency. This presentation usually occurs after the onset of pulmonary disease. Renal function can range from normal to rapidly decreasing over a few weeks to months. Rapidly progressive glomerulonephritis (RPGN), frequently seen in Goodpasture syndrome, is characterized by a glomerular filtration rate that decreases by one half or a serum creatinine that doubles in 3 months or less (Bolton, 1996).

To diagnose Goodpasture syndrome, pulmonary hemorrhage and glomerulonephritis demonstrated by classic linear deposits of anti-GBM antibody on renal biopsy tissue must be present (Couser, 1988). Indirect immunofluorescence microscopy, enzyme-linked immunosorbent assays (ELISAs), antineutrophil cytoplasmic antibodies (ANCA), and an anti-GBM antibody titer are ordered to confirm the diagnosis and provide a guide for therapy and possible future renal transplantation (Couser, 1988). Pulmonary iron sequestration usually will produce an iron deficiency anemia; therefore, obtaining a hematocrit (HCT) level, hemoglobin (HgB) level, and an iron level may be helpful (Couser, 1988). A white blood cell (WBC) count may useful in determining if there is an active inflammatory process (Avella & Walker, 1999). A creatinine and blood urea nitrogen (BUN) level and a urinalysis (UA) will aid in detecting renal disease. Renal disease in this disorder will usually progress rapidly to renal failure in hours to weeks, thus initial results are imperative to assess progression. An elevated erythrocyte sedimentation rate (ESR) indicates an inflammatory process. This is very uncommon in Goodpasture syndrome, however, it is common in patients with systemic vasculitis (Ball & Young, 1998). These data aid in the differential diagnoses of pulmonary-renal diseases.

Antineutrophil cytoplasmic antibodies (ANCA) help differentiate Goodpasture syndrome from other diseases. These are antibodies directed against the granules and lysosomes of neutrophils. ANCA can be divided into two distinct immunofluorescence patterns. Cytoplasmic antineutrophil antibodies (c-ANCA) are directed against cytoplasmic antigens in neutrophils (Jennette, Hoidal, & Falk, 1990). Perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) are primarily directed against myeloperoxidase (Falk & Jennette, 1988), which aggregates around the nuclear membrane of neutrophils. ANCA are primarily associated with Wegener's granulomatosis, microscopic polyangiitis, idiopathic necrotizing glomerulonephritis, Churg-Strauss syndrome, certain gastrointestinal disorders, and rheumatic disorders (Rose, Kaplan, & Appel, 1999). Thus, ANCAs are generally not detected in Goodpasture syndrome. However, one third of patients with Goodpasture syndrome will have positive ANCAs at some point in the illness (Bosch et al., 1991). Also, there are reports of patients with vasculitis who have positive anti-GBM antibodies and positive p-ANCAs (Wahls, Bonsib, & Schuster, 1987); however, these patients are found to have low anti-GBM titers (Jayne, Marshall, Jones, & Lockwood, 1990).

Serum antinuclear antibodies (ANA) help differentiate Goodpasture syndrome from systemic lupus. The ANA titer detects autoantibodies that are mainly in the nucleus of cells. Ninety-five percent of patients with SLE show a positive ANA titer, while Goodpasture syndrome patients show a negative titer (D'Agati, 1998).

Circulating anti-GBM antibodies are detected by using an ELISA. The ELISA detects the binding of serum immunoglobulin to natural or synthetic antigens prepared from basement membrane (Netzer et al., 1998). Anti-GBM antibody titer must be greater than 20 units to be considered positive (Avella & Walker, 1999).

Pulmonary. Chest x-ray shows alveolar-type shadowing with sparing of the upper lung fields secondary to lung hemorrhage (Kluth & Rees, 1999). Another assessment of lung involvement is measurement of the carbon monoxide uptake. The test used is the diffusing capacity for carbon monoxide (DLCO), which is a measure of the diffusion capability of the lung corrected for lung volume (Ball & Young, 1998). The DLCO is increased in lung hemorrhage because of binding of hemoglobin to carbon monoxide (Ball & Young, 1998). Computed tomography (CT) and magnetic resonance imaging (MRI) scanning are not necessary in the evaluation of lung involvement unless diagnosis is questionable (Ball & Young, 1998).

Urinalysis. Urinalysis findings in progressive Goodpasture syndrome consist of red blood cell casts, macroscopic hematuria, dysmorphic red blood cells, and proteinuria, generally less than 3 g/24 hours (Kluth & Rees, 1999). Red blood cell casts in the urine suggest glomerulonephritis and parenchymal bleeding. Casts are made of red blood cells that are encased in a tubular shaped cast matrix. Red blood cell casts are often seen with hematuria, proteinuria, and dysmorphic red blood cells in Goodpasture syndrome (Avella & Walker, 1999).

Renal biopsy. To confirm Goodpasture syndrome, a renal biopsy is required with results obtained from light microscopy, electron microscopy, and immunofluorescence.

As stated above, Goodpasture syndrome is usually progressive and rapid. If a patient with Goodpasture syndrome has only mild renal failure, examination of the biopsy specimen by light microscopy may show focal and segmental glomerular hypercellularity, segmental necrosis of the glomeruli, and small crescents (see Figure 1). This disease often progresses to the crescentic glomerulonephritis, in which case light microscopy shows a lack of endocapillary proliferation, edema, leukocyte infiltration, and circumferential crescents (Brenner & Rector, 1996). Light microscopy cannot differentiate Goodpasture syndrome from other causes of crescentic glomerulonephritises; therefore, electron microscopy examination and immunofluorescence of the biopsy specimen are needed.

Electron microscopy shows widening of subendothelial spaces of glomerular capillaries, which is related to the binding of anti-GBM antibodies (Brenner & Rector, 1996). AntiGBM antibodies attach to the GBM because of the presence of Type IV collagen. Electron microscopy also shows openings in the GBM and Bowman's capsule (Brenner & Rector, 1996). These openings allow fibroblasts to enter Bowman's space, which promotes crescent formation (Brenner & Rector, 1996). Crescents are created by parietal cells and macrophages in combination with GBM destruction as discussed above (Kluth & Rees, 1999). Also, according to Kluth and Rees (1999), the crescents are generally in the same stage of development.

Immunofluorescence of the biopsy specimen will exhibit linear deposits of IgG, IgA, and/or IgM outlining the capillary loops. Also, C3 usually is present in an interrupted linear fashion (Brenner & Rector, 1996). The presence of C3 in a granular pattern in the capillaries can be related to a coexisting membranous glomerulonephritis (Brenner & Rector, 1996). Other diseases can demonstrate linear staining, including diabetic nephropathy, Alport's syndrome, lupus nephritis, and renal transplant biopsy specimens (Kluth & Rees, 1999).

Lung biopsy. Sometimes a lung biopsy is needed to exclude other diagnoses such as infection or other renal-pulmonary diseases. Lung biopsy will demonstrate extensive nonspecific intra-alveolar hemorrhage, hemosiderin-laden macrophages, and occasionally, linear immunofluorescence as seen in the kidney (Ball & Young, 1998).

Differential Diagnoses

Multiple diseases may produce pulmonary renal syndromes and renal failure, such as Wegener's granulomatosis, Henoch-Schonlein purpura, lupus nephritis, and polyarteritis nodosa. Salient features of these diseases that help differentiate them from Goodpasture syndrome are summarized in Table 1.
Table 1.
Differential Diagnosis in Goodpasture Syndrome

   Differential         History                  Physical Exam
     Diagnoses

Wegener's             Malaise                  Leukocytosis
Granulomatosis        Fever                    Nasal crusting
                      Weight loss              Purulent nasal
Clinically            Cough                    drainage
characterized         Hemoptysis               Possible saddle nose
by a triad of         Dyspnea/SOB              deformity
GN, upper and         Chest discomfort         Purpura
lower respiratory     Weakness                 Peripheral neuropathy
tract lesions         Muscle pain              Ocular inflammation
(Abuello, 1995)       Epistaxis                Ear inflammation
                      Sputum production
                      Pleuritic pain

Henoch Schonlein      Arthralgias              Purpuric rash over
Purpura               Abdominal pain           buttocks and extensor
                      secondary to             surfaces of arms and
IgA immune complex    GI bleed Renal           legs; may extend to
mediated vasculitis   involvement 50%          other areas of body
(Abuello, 1995)

Lupus Nephritis       Fever                    Butterfly rash over
                      Rash                     cheeks and bridge
Immune complex        Arthralgias              of nose Oral and
disease.              Arthritis                nasal ulcers
One of the most       Alopecia                 Cutaneous lesions
frequent              Raynaud phenomenon       Nail lesions,
manifestations                                 ridging, and pitting
of SLE
(Abuello, 1995)

Polyarteritis Nodosa  Malaise                  Fever

A vasculitis of
small and
medium sized
arteries
(Abuello, 1995)

   Differential         Lab Data                 Biopsy Data
     Diagnoses

Wegener's             Thrombocytosis           Segmental fibrinoid
Granulomatosis        Elevated alkaline        necrosis
                      phosphatase              and crescent
Clinically            Elevated ESR             formation
characterized         + ANCA
by a triad of
GN, upper and
lower respiratory     With renal
tract lesions         involvement:
(Abuello, 1995)       Eosinophilia or +
                      Rheumatoid factor

Henoch Schonlein      Nephritis after          IgA deposits in
Purpura               initial symptoms         skin lesions or in
                      subside                  the renal mesangium
IgA immune complex
mediated vasculitis
(Abuello, 1995)

Lupus Nephritis       + ANA                    Immune deposits
                      + double stranded        Influx of leukocytes
Immune complex        DNA                      Glomerular necrosis
disease.              Microhematuria           or scarring
One of the most       Mild proteinuria         Glomerular
frequent              or nephrotic syndrome    proliferation
manifestations        or rapidly progressive
of SLE                glomerulonephritis
(Abuello, 1995)       (RPGN)

Polyarteritis Nodosa  Anemia

A vasculitis of
small and
medium sized
arteries
(Abuello, 1995)

GN=Glomerulonephritis

ANA=Antinuclear antibody

ESR=Erythrocyte Sedimntation Rate

DNA=Deoxyribonucleic acid

ANCA=Antineutrophil cytoplasmic antibodies

Note: From Abuelo, J.G. (Ed.) (1995). Renal failure,
diagnosis and treatment. Boston: Kluwer Academic Publishers.
Used with permission.


Patient Management

To treat Goodpasture syndrome, a bilateral nephrectomy was commonplace before the 1980s. Currently, treatment is focused on plasmapheresis and immunosuppression. The goals for treatment are to remove circulating antibodies, stop further production of antibodies, and remove any antigens that stimulate antibody formation (Young & Ball, 1998).

Plasmapheresis, or therapeutic plasma exchange (TPE), is an extracorporeal process that decreases large molecular weight substances in the blood, including complement and anti-GBM antibodies. As this removal is taking place, a replacement fluid is used to maintain hemodynamic stability. The replacement fluid used for patients with Goodpasture syndrome is albumin. Removed plasma is replaced ml for ml with 50% albumin (Ismail, 2000)

Uncontrolled studies have reported that TPE will stop progression to dialysis dependency in 40% of patients with Goodpasture syndrome (Madore, Lazarus, & Brady, 1996). TPE for Goodpasture syndrome is considered art emergency treatment, because TPE is less effective when serum creatinine is greater than 7.0 mg/dl or after oliguria develops (Ismail, 2000). TPE is conducted with an apheresis machine, preferably through a femoral dual-lumen catheter to achieve prescribed blood flow. Several different TPE schedules can be used. The usual schedule is 2 to 4 liter exchanges daily or every other day for 7 to 14 days.

Although TPE will greatly reduce anti-GBM antibodies, there are severe complications of this treatment. According to Mokrzycki and Kaplan (1994), adverse reactions are more common with fresh frozen plasma (FFP) than with albumin replacement as used in the treatment of Goodpasture syndrome. However, the most common complication is citrate-induced paresthesias. Citrate is infused as an anticoagulant for the extracorporeal system, and it binds and lowers ionized calcium. This reaction can be reduced by infusing one 10 ml ampule of 10% calcium chloride over 15-30 minutes, 15 minutes after the start of plasma exchange (Kaplan & Halley, 1990). Another complication of citrate is citrate metabolic alkalosis because metabolism of excess citrate generates bicarbonate (Pearl & Rosenthal, 1985).

Hypotension is also a complication of TPE. During TPE, 15% percent of the patient's intravascular volume is within the extracorporeal system; some systems require a higher percentage. Lowering the patient's head, IV fluids, and/or temporarily ceasing the procedure usually can return the patient to a normotensive state.

Respiratory distress during TPE usually is related to fluid overload. Pulmonary emboli can be of concern, although new technology in TPE cell separators and anticoagulation therapy makes this a rare occurrence (Kaplan & Fridey, 1999). Allergic reaction to the ethylene oxide gas, which is used as a membrane sterilant, or complement-mediated reaction to the membranes can cause dyspnea and chest pain (Jorstad, 1987). The treatment includes antihistamines, epinephrine, and corticosteroids.

As explained above, albumin is used as the replacement fluid during TPE for Goodpasture syndrome. Using albumin produces a decrease in clotting factors that can increase bleeding. According to Kaplan and Halley (1990), the prothrombin time (PT) increases by 30% and partial thromboplastin time (PTT) doubles. This will occur after a single plasma volume exchange but will return to normal within 4 hours. However, with repeated plasma exchanges, the increase in PT and PTT can stay elevated. For this reason, it is suggested that FFP be substituted as the replacement fluid in patients at risk of bleeding (Kaplan & Fridey, 1999).

Infection is a risk for the patient undergoing TPE secondary to removal of immunoglobulins and complement, and use of immunosuppressive medications as explained below. If severe infection occurs, a single infusion of intravenous immune globulin (100-400 mg/kg) is needed (Kaplan & Fridey, 1999).

Immunosuppressive therapy is used in conjunction with TPE. The usual combination of drugs is corticosteroids and cyclophosphamide. Patients usually are initiated on pulse methylprednisolone 30 mg/kg IV over 20 minutes every other day for three doses followed by daily oral prednisone 1 mg/kg every day and cyclophosphamide 2 mg/kg every day (Rose, Kaplan, & Appel, 1999). Recommendations are that cyclophosphomide be discontinued if the WBC count drops below 3.5 x [10.sup.9]/microliter (Kluth & Rees, 1999). With this combination of drugs and TPE, anti-GBM titers usually decline at a rapid rate and are negative after a median time of 2 months (Merkel et al., 1994). However, some clinicians recommend continuing immunosuppressive therapy for 3 months even after negative antibodies are determined (Netzer et al., 1998). Other clinicians recommend continuing immunosuppression for a full year to minimize the risk of relapse (Bolton, 1996). Consecutive negative anti-GBM titers indicate remission.

The previous regimen is suggested for patients with a serum creatinine below 7.0 mg/dl. Patients with serum creatinine levels greater than 7.0 mg/dl may be in need of dialysis immediately upon presentation. These patients will not likely respond to TPE, and TPE should be discontinued if anti-GBM titers do not respond to aggressive therapy (Ball & Young, 1998).

Historically, the prognosis for Goodpasture syndrome has been poor. With the advent of plasmapheresis, immunosuppression, and improved serologic tests for earlier recognition of the disease, the prognosis has improved dramatically resulting in long-term survival. However, the degree of renal function and the percent of crescents on renal biopsy are better predictors of outcome than which therapy is used (Ball & Young, 1998).

Renal Transplant

According to Ball and Young (1998), renal transplantation can be used in patients with ESRD secondary to Goodpasture syndrome.

Uncontrolled studies have demonstrated improved outcomes and decreased risk of Goodpasture syndrome recurring if renal transplantation occurs after autoantibodies have become undetectable. If autoantibody production has ceased after 9 to 12 months, renal transplantation can be scheduled with a low recurrence rate of the original disease in the graft (less than 5% in the 1990s) (Netzer et al., 1998). Improved immunosuppressive therapy and delaying the transplant until autoantibody production has ceased attribute to the low percentage of recurrence.

Accumulated information about Goodpasture syndrome indicates that patients who receive transplants have outcomes comparable to patients with other causes of ESRD. Early identification and early treatment of relapse is the challenge faced by clinicians to save the graft (Netzer et al., 1998).

Summary

Goodpasture syndrome is a rare and complex disease that can be fatal if not recognized rapidly and treated aggressively. It is suspected if a patient presents with signs of progressive renal failure combined with pulmonary alterations. The detection of anti-GBM antibodies in the circulating blood, kidneys, and lungs along with the presence of RPGN requires prompt initiation of treatment. Information about the pathogenesis of this disease is evolving, as new discoveries are being made every year; however, no preventive measures for anti-GBM-induced GN have been developed. To ensure prompt recognition and early therapy, it is essential that clinicians stay abreast of current literature and treatment modalities.

Acknowledgment: Thanks to April Zarifian, MSN, RN, CNN, for her contributions to this manuscript.

References

Abuelo,J.G. (Ed.). (1995). Renall failure, diagnosis and treatment. Boston: Kluwer Academic Publishers.

Avella, P., & Walker, M. (1999). Goodpasture's syndrome: A nursing challenge. Dimensions of Critical Care Nursing 18,(2), 2-7.

Ball, J.A., & Young, K.P. (1998). Palmonary manifestations of Goodpasture's syndrome. Clinics in Chest Medicine, 19(4), 777-791.

Bolton, W.K. (1996). Goodpasture's syndrome. Kidney International, 50, 1753-1766.

Bosch, X., Mirapeix, E., Font, J, Borrellas, X., Rodriguez, P., Lopez-Soto, A., Ingelmo, M., & Revert, L. (1991). Prognostic implication of anti-neutrophil cytoplasmic autoantibodies with myeloperoxidase specificity in anti-glomerular basement membrane disease. Clinical Nephrology, 36, 107-113.

Brenner, B.M., & Rector, F.C. (1996). The kidney. Philadelphia: WB. Saunders.

Couser, W.G. (1988). Rapidly progressive glomerulonephritis: Classification, pathogenetic mechanisms, and therapy. American Journal of Kidney Diseases, 11(6), 449-464.

D'Agati, V.D. (1998). Renal disease in systemic lupus erythematosus, mixed connective tissue disease, Sjogren's syndrome, and rheumatoid arthritis. In J. Jennette, j. Olsen, M. Shwartz, & E Silva (Eds.), Heptinstall's pathology of the kidney (5th ed., Vol. II) (pp. 630-640). Philadelphia: Lippincott Raven.

Donaghy, M., & Rees, AJ. (1983). Cigarette smoking and lung haemorrhage in glomemlonephritis caused by autoantibodies to glomerular basement membrane. Lancet, 2, 1390-1393.

Falk, RJ., & Jennette, J.C. (1988). Anti-neutrophil cytoplasmic autoantibodies with specificity for myeloperoxidase in patients with systemic vasculitis and idiopathic necrotizing and crescentic glomemlonephritis. New England Journal of Medicine, 318, 1651-1657.

Hellmark, T., Segelmark, M., & Wieslander, J. (1997). Anti-GBM antibodies in goodpasture syndrome; anatomy of an epitope. Nephrology, Dialysis and Transplantation, 12(4), 646-648.

Ismail, N. (2000, April). Plasmapheresis. Paper presented at the meeting of Vanderbilt University Nephrology Nursing, Nashville, TN.

Jayne, D.W., Marshall, P.D., Jones, S.J., & Lockwood, J. (1990). Autoantibodies to GBM and neutrophil cytoplasm in rapidly progressive glomerulonephritis. Kidney International, 37, 965- 970.

Jennette, J.C., Hoidal, J.R., & Falk, R.J. (1990). Specificity of anti-neutrophil cytoplasmic autoantibodies for proteinase 3. Blood, 75, 2263-2264.

Jorstad, S. (1987). Biocompatibility of different hemodialysis and plasmapheresis mem branes. Blood Purification, 5, 123-126.

Kaplan, A.A., & Fridey, J.L. (December 1999). Complications of therapeutic plasma exchange. Up to date library [On-line]. Available: www.uptodate.com/html/ spec/neph/toc.htm

Kaplan, A.A., & Halley, S.E. (1990). Plasma exchange with a rotating filter. Kidney International 38, 160-166.

Kluth, D.C., & Rees, AJ. (1999). Anti glomerular basement membrane disease. Journal of the American Society of Nephrology, 10(11), 2446-2453.

Madore, E, Lazarus, J.M., & Brady, H.P. (1996). Therapeutic plasma exchange in renal diseases. Journal of the American Society of Nephrology, 7(3), 367-386.

Merkel, F., Pullig, O., Marx, M., Netzer, K.O., & Weber, M. (1994). Course and prognosis of anti-basement membrane antibodymediated diseases: Report of 35 cases. Nephrology, Dialysis and Transplantation, 9, 372-376.

Mokrzycki, M.H., & Kaplan, A.A. (1994). Therapeutic plasma exchange: Complications and management. American Journal of Kidney Diseases, 23, 817-827.

Neilson, E.G., Kalluri, R., Sun, M.J., Gunwar, S., Danoff, T., Mariyana, M., Myers,J.C., Reeders, S.T., & Hudson, B.G. (1993). Specificity of Goodpasture autoautibodies for the recombinant noncollagenous domains of human type IV collagen. Journal of Biological Chemistry, 268, 8402-8405.

Netzer, K., Merkel, E, & Weber, M. (1998). Goodpasture syndrome and end-stage renal failure-to transplant or not to transplant? Nephrology, Dialysis, and Transplantation, 13, 1346-1348.

Pearl, R.G., & Rosenthal, M.H. (1985). Metabolic alkalosis due to plasmapheresis. American Journal of Medicine, 79, 391-403.

Queluz, T.H., Pawlowski, I., & Brunda, MJ. (1990). Pathogenesis of an experimental model of goodpasture's hemorrhagic pneumonitis. Journal of Clinical Investigation, 85, 1507-1512.

Rose, B.D., Kaplan, A.A., & Appel, G.B. (1999). Treatment of anti-GBM antibody disease. Up to date library [On-line]. Available: www.uptodate.com/ html/spec/neph/toc.htm

Stanton, M.C., & Tange, J.D. (1958). Goodpasture's syndrome: Pulmonary haemorrhage associated with glomerulonephritis. Australasian Annals of Medicine, 7, 132-144.

Wahls, T.L., Bonsib, S.M., & Schuster, V.L. (1987). Coexistent wegener's granulomatosis and anti GBM disease. Human Pathology, 18, 202-205.

Goodpasture Syndrome: Pathophysiology, Diagnosis, and Collaborative Management

By Hope L. Fox and Dawn Swann

Posttest -- 1.7 Contact Hours Posttest Questions

(See posttest instructions on the answer form, next page) The Editor gratefully acknowledges Carol K. Annis, RN, CNN, for her contributions to the questions in this CE posttest.
1. Goodpasture syndrome is characterized
   by
   A. elevated anti-GBM antibodies and pulmonary
   hemorrhage.

   B. the presence of anti-ANCA antibodies
   and microscopic polyangiitis.

   C. decreased erythrocyte sedimentation
   rate (ESR) and pulmonary emboli,

   D. presence of cytoplasmic antibodies
   and purpuric rash.

2. Which of the following have a higher
   incidence of Goodpasture syndrome?

   A. White males less than 25 years old.

   B. 60 year old African-American males.

   C. African-American females greater than 20.

   D. 30-year-old white males.

3. What is the most frequent underlying
   pulmonary compromise associated
   with development of pulmonary hemorrhage
   in Goodpasture syndrome?

   A. Upper respiratory tract infection.

   B. Endotoxins.

   C. Smoking.

   D. Volume overload.

4. Lung injury in Goodpasture syndrome
   is thought to be related to

   A. increase in alveolar capillary permeability.

   B. decreased pulmonary capillary pressure.

   C. injury to alveolar capillary fenestration.

   D. hemorrhage causing decreased diffusion.

5. S.W., a 35 year old white female, is
   admitted to your hospital floor with a
   diagnosis of Goodpasture syndrome.
   This client is most likely to have what
   symptoms?

   A. Chest pain and arthralgia

   B. Joint pain and bacteremia.

   C. Vasculitis and pleurisy.

   D. Shortness of breath and cough.

6. Rapidly progressive glomerular nephritis
   (RPGN) frequently occurs with
   Goodpasture syndrome, RPGN is characterized
   by

   A. anti-GBM antibody titer greater than 20
   units.

   B. serum creatinine that doubles in 3
   months or less.

   C. glomerular filtration rate that decreases
   by 25%.

   D. positive antineutrophil cytoplasmic
   antibodies.

7. G.M., a 35 year old white male, presents
   with initial complaints of
   fatigue, hemoptysis, and hematuria.
   He smokes 1-2 packs of cigarettes a
   day. Lab results are as follows: creatinine
   2.7 mg/dl, BUN 40 mg/dl, [K.sup.+] 5.2
   mEq/l, Hgb 10 g/dl, Hct 30 %, WBC 6.0
   [micro]l. The differential diagnosis includes
   Goodpasture syndrome. Upon evaluation
   of these findings the nurse recognizes
   that G.M.

   A. is at high risk for development of
   pneumonia.

   B. is at high risk for alveolar hemorrhage.

   C. should be scheduled for therapeutic
   plasma exchange (TPE).

   D. should be scheduled for immediate
   dialysis.

8. G.M. is scheduled for a renal biopsy.
   What findings must be present on the
   renal biopsy for a diagnosis of
   Goodpasture syndrome?

   A. Narrowing of subendothelial spaces of
   glomerular capillaries.

   B. Endocapillary proliferation with
   parenchymal bleeding.

   C. Dysmorphic red blood cells in
   endothelial spaces.

   D. Linear deposition of anti-GBM
   antibodies.

9. The purpose of therapeutic plasma
   exchange (TPE) is to

   A. stop production of autoantibodies.

   B. avoid the use of immunosuppressive
   therapy.

   C. remove circulating autoantibodies.

   D. reduce the risk of infection associated
   with Goodpasture syndrome.

10. S.B., a 47 year old male, is admitted
   with Goodpasture syndrome and presents
   with oliguria and a creatinine of
   7.8 mg/dl. The best treatment for S.B.
   would be

   A. immunosuppression alone.

   B. immediate dialysis.

   C. TPE if autoantibodies are increasing.

   D. TPE daily for 1 week.

11. During the TPE procedure the nurse
   should be alert for which most common
   complication of TPE?

   A. Paresthesias.

   B. Infection.

   C. Metabolic acidosis.

   D. Pulmonary emboli.

12. Your choice for the replacement fluid
   initially used for TPE in a patient with
   Goodpasture syndrome is based on
   which principle?

   A. Albumin provides improved protection
   against infection.

   B. FFP is more compatible with citrate,

   C. Adverse reactions are less common
   with albumin than FFP

   D. FFP decreases the risk of hypotension.

13. A patient with a diagnosis of
   Goodpasture syndrome asks you,
   "How long will I have to take the
   immunosuppressive drugs?" Your
   best response is

   A. "To minimize the risk of relapse, drug
   therapy may continue for up to a full
   year."

   B. "To reduce the risk of infection, drug
   therapy is stopped 1 week after
   autoantibody production ceases."

   C. "Drug therapy will continue until the
   WBC count drops below 3.5 x 10 [micro]l."

   D. "Drug therapy will continue until transplantation
   is scheduled."

14. A new patient at your clinic with a
   diagnosis of Goodpasture syndrome
   asks you about renal transplantation.
   Your best response is

   A. "You may be considered for transplantation
   after TPA therapy is complete."

   B. "Transplantation may stimulate
   autoantibody recurrence."

   C. "Transplantation should be delayed for
   9-12 months after autoantibody production
   has ceased."

   D. "Transplantation should be avoided
   until preventative measures for antiGBM-induced
   GN are developed."

15. Early diagnosis and treatment of
   Goodpasture syndrome is important
   because

   A. delayed treatment can lead to SLE.

   B. delayed treatment can lead to vasculitis.

   C. prompt therapy can prevent RPGN.

   D. prompt therapy can decrease disease
   progression.


ANSWER FORM Goodpasture Syndrome: Pathophysiology, Diagnosis, and Collaborative Management

By Hope L. Fox and Dawn Swann

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Hope L. Fox, MSN, RN, is Renal Administrator, Wisconsin Renal Care Group, Milwaukee, WI.

Dawn Swann, MSN, RN, is Nurse Practitioner, Nephrology and Hypertension Consultants, Anniston, AL.
COPYRIGHT 2001 Jannetti Publications, Inc.
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2001 Gale, Cengage Learning. All rights reserved.

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Author:Fox, Hope L.; Swann, Dawn
Publication:Nephrology Nursing Journal
Geographic Code:1USA
Date:Jun 1, 2001
Words:5110
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