Goodpasture's syndrome

Goodpasture's syndrome is an immunologic disorder characterized by glomerulonephritis, pulmonary hemorrhage and anti-glomerular basement membrane (GBM) antibody formation. [1] Although most patients have some degree of proteinuria, frank nephrosis is distinctly unusual. [1,2] Furthermore, renal vein thrombosis has not been reported, to our knowledge, as the initial presentation of Goodpasture's syndrome.

We report a patient who presented with renal vein thrombosis and nephrosis that progressed to pulmonary hemorrhage and renal failure. Results of renal biopsy and serum anti-GBM assay confirmed the diagnosis of Goodpasture's syndrome. This unique presentation contributed to the delay in correct diagnosis and initiation of appropriate therapy.

CASE REPORT

A 23-year-old woman presented with leg edema and left flank tenderness. Serum blood urea nitrogen was 13 mg/dl, creatinine 1.4 mg/dl, albumin 2.2 g/dl and cholesterol 276 g/dl. Urinalysis revealed 4+ proteinuria. A renal venogram demonstrated left renal vein thrombosis (Fig 1). Chest radiograph showed subtle bilateral alveolar infiltrates, which were ascribed to nephrosis and volume overload. Renal vein thrombosis secondary to the nephrotic syndrome was diagnosed and the patient was treated with intravenous heparin that was converted to coumadin at discharge.

Two weeks later, the patient was readmitted with severe dyspnea, anasaca, oliguria, cough productive of blood-tinged sputum, and nausea. A chest radiograph showed bilateral alveolar infiltrates most marked in the lower and mid lung zones (Fig 2). Blood urea nitrogen was 111 mg/dl; creatinine, 10 mg/dl; potassium, 7.2 mmol/L; and hematocrit, 10.7 percent. Urinalysis revealed 4+ proteinuria and hematuria. The patient was intubated because of progressive hypoxemia and transferred to the Medical University of South Carolina. Endotracheal secretions were blood-tinged and contained numerous hemosiderin-laden macrophages.

Following stabilization with hemodialysis, a renal biopsy specimen was obtained that showed 75 percent of glomeruli involved with crescentic glomerulonephritis and linear deposition of IgG and [C.sub.3] in basement membranes. Serum anti-GBM titer by radioimmunoassay was 1:256. The patient was treated with corticosteroids, cyclophosphamide and plasmapheresis with resolution of pulmonary infiltrates and respiratory failure. Three weeks later, she was discharged, requiring chronic hemodialysis for oliguric renal failure.

DISCUSSION

Renal vein thrombosis is a well-recognized complication of nephrotic syndrome. Although the precise mechanism is unknown, vascular thrombosis appears to be a consequence of the hypercoagulable state that accompanies nephrosis rather than a cause, as was previously suspected, of the renal lesions. [3-5] in adults, renal vein thrombosis most commonly occurs with membranous and membranoproliferative glomerulonephritis, [6,8] and associations with renal sarcoidosis, amyloidosis, [3] lupus nephritis [3,8] and sickle cell anemia [9] have also been described. To our knowledge, renal vein thrombosis has not been previously reported in a patient with nephrosis associated with Goodpasture's syndrome.

We suspect that renal vein thrombosis in our patient resulted from anti-GBM-related nephrosis that preceded the more typical features of Goodpasture's syndrome, such as frank alveolar hemorrhage and azotemia. Nepthrotic syndrome has been noted infrequently as a complication of Goodpasture's syndrome, probably because of the typically fulminant course of renal insufficiency that occurs in anti-GBM disease. [1] This rapid course may also underlie the apparent rarity of renal vein thrombosis in patients with Goodpasture's syndrome.

Other etiologies of pulmonary hemorrhage and glomerulonephritis have been described. These include Wegener's granulomatosis, systemic lupus erythematosus, Henoch-Schonlein purpura, and cryoglobulinemia. Although there is an immunologic basis to these disorders, circulating anti-GBM antibodies have not been demonstrated. [10]

This unique presentation of Goodpasture's syndrome contributed to the delay in correct diagnosis of the present patient. Furthermore, the administered anticoagulation therapy for renal vein thrombosis may have exacerbated the pulmonary hemorrhage and eventual degree of respiratory failure.

In summary, renal vein thrombosis secondary to nephrosis is an unusual but important initial presentation of Goodpasture's syndrome. Failure to detect the underlying disorder may prompt initiation of inappropriate therapy for thrombosis, such as anticoagulant drugs, thereby aggravating the degree of respiratory failure from subsequent alveolar hemorrhage.

REFERENCES

[1] Glassock RJ, Cohen AH, Adler, SG. Secondary glomerular diseases. In: Brenner BM, Rector Jr, RJ, eds. The kidney. 3rd ed. Philadelphia: W.B. Saunders, Co.; 1986:1032-36

[2] Robinson T, Rabinowitz JG. The nephrotic syndrome. Radiol Clin North Am 1972; 10:495-510

[3] Llach F, Papper S, Massry SG. The clinical spectrum of renal vein thrombosis: acute and chronic. Am J Med 1980; 69:819-27

[4] Harrington JT, Kassirer JP. Renal vein thrombosis. Ann Rev Med 1982; 33:255-62

[5] Humphreys JT, Alfrey AC. Vascular diseases of the kidney. In: Brenner BM, Rector Jr, RJ, eds. The kidney, 3rd ed. Philadelphia: W.B. Saunders, 1986:1180-84

[6] Llach F, Arieff AI, Massry SG. Renal vein thrombosis and nephrotic syndrome. A prospective study of 36 adult patients. Ann Intern Med 1975; 83:8-14

[7] Llach F, Koffler A, Finck E, Massry SG. On the incidence of renal vein thrombosis in the nephrotic syndrome. Arch Intern Med 1977; 137:333-36

[8] Appel GB, Williams GS, Meltzer JI, Pirani CL. Renal vein thrombosis, nephrotic syndrome, and systemic lupus erythematosus. Ann Intern Med 1976; 85:310-17

[9] Strom T, Muehrcke RC, Smith RD. Sickle cell anemia with the nephrotic syndrome and renal vein obstruction. Arch Intern Med 1972; 129:104-08

[10] Albelda SM, Gefter WB, Epstein D, Miller WT. Diffuse pulmonary hemorrhage: a review and classification. Radiology 1985; 154:289-97

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