Penicillamine nephropathy in rheumatoid arthritis. A clinical, pathological and immunological study

Fourteen patients who developed persistent proteinuria while on penicillamine for rheumatoid arthritis, were collected over a period of one year. Eleven patients had a frank nephrotic syndrome and three had a lesser degree of proteinuria but no oedema. The patients had received penicillamine (mean daily dose 1015 mg) for less than one year (mean 7-5 months) when the nephropathy was detected. Clinical investigations have been correlated with renal biopsy material. Light microscopy detected no abnormalities except for minimal hypercellularity in a few patients. In markde contrast, the electron-microscope revealed numerous electron-dense deposits (EED's) in the outer layer of the basement membrane. Immunofluorescence showed the presence of IgG and complement in the basement membrane, the intensity of which correlated with the number of EED's. The pathological picture was essentially the same in those patients with the nephrotic syndrome and those with proteinuria. In this series, we found no evidence that penicillamine induced renal damage by any other mechanism except immune complex deposition. Serological tests revealed little evidence for complement activation or consumption and platelet aggregation was the only positive direct test for circulating immune complexes. Renal biopsies were performed at differing intervals after the cessation of penicillamine therapy, which allowed assessment of the natural history of the pathological lesion and revealed a striking persistence of EDD's in some patients. Two patients showed an almost identical picture initially and at re-biopsy one year later. Persistent proteinuria was also a feature of the group as a whole. The pathological picture has similarities with that of idiopathic membranous glomerulopathy. This study suggests that the use of penicillamine in rheumatoid arthritis may induce persistent renal damage.