Conversion of Goodpasture's syndrome into membranous glomerulonephritis

An autoimmune response to the non‐collagenous NC‐1 domain of the α3‐chain of type IV collagen is the pathogenetic basis for the development of anti‐glomerular basement membrane (GBM) disease. In Goodpasture's syndrome clinical involvement of both kidneys and lungs is present. In rare cases an association of Goodpasture's syndrome/anti‐GBM disease with membranous glomerulonephritis has been reported [1,2]. In all of these cases an initially membranous glomerulonephritis evolved into Goodpasture's syndrome. Based on these clinical observations, it has been hypothesized that damage to the GBM in the course of membranous glomerulonephritis may have resulted in the release of normal or altered basement membrane material, leading to the formation of anti‐GBM antibodies [2]. Here we describe a patient in whom the sequence of events was reversed, i.e. he presented with Goodpasture's syndrome and subsequently developed membranous glomerulonephritis. A 17‐year‐old Caucasian male with an unremarkable medical history presented in November 1996 with his first episode of haemoptysis. The patient had smoked 15 cigarettes per day for the last 3 years, had no exposure to solvents or heavy metals, including mercury, and no preceding infections. A chest X‐ray taken by his family doctor in November 1996 showed patchy infiltrates in both lungs (Figures 1a). Due to persistent haemoptyses and the development of exertional dyspnoea, the patient was admitted to a regional hospital on 11 December 1996. Upon admission the physical examination was significant for shortness of breath at rest and tachycardia (100/min) but was otherwise unremarkable. Laboratory evaluation revealed marked anaemia (haemoglobin 9.5 mg/dl) and an increased sedimentation rate (30/58) but no leukocytosis. Blood gas analysis showed hypoxia (arterial pO2 44 Torr, O2 saturation 80%). Urine dipstick testing was positive for blood and leukocytes, but not for protein. An Addis count showed massive erythrocyturia. Under the assumption of a pulmonary infection, the patient received gentamicin (160 mg), cefoxitin (3×2 g), and roxithromycin (2×300 mg) from 11–17 December. This was followed by rapid clinical improvement and resolution of the pulmonary infiltrates (Figures 1b). At this time a test for anti‐GBM‐antibodies registered positive. The presence of anti‐GBM antibodies was evaluated by ELISA using human α3(IV) NC1 as an antigen (Laboratory Dr Limbach, Heidelberg, Germany). Specificity of the test for anti‐GBM antibodies was confirmed by prior incubation of the serum with soluble α3(IV) NC1 for 30 min. On 20 December 1996 the patient was transferred to our hospital for further nephrological evaluation and treatment.