PENICILLAMINE NEPHROPATHY IN RHEUMATOID-ARTHRITIS - CLINICAL, PATHOLOGICAL AND IMMUNOLOGICAL STUDY

Abstract

Fourteen patients who developed persistent proteinuria while on penicillamine for rheumatoid arthritis were collected over a period of 1 yr. Eleven patients had a frank nephrotic syndrome and 3 had a lesser degree of proteinuria but no edema. The patients had received penicillamine (mean daily dose 1015 mg) for less than 1 yr (mean 7.5 mo.) when the nephropathy was detected. Clinical investigations were correlated with renal biopsy material. Light microscopy detected no abnormalities except for minimal hypercellularity in a few patients. In marked contrast, EM studies revealed numerous electron-dense deposits (EDD) in the outer layer of the basement membrane. Immunofluorescence showed the presence of Ig[immunoglobulin]G and complement in the basement membrane, the intensity of which correlated with the number of EDD. The pathological picture was essentially the same in those patients with the nephrotic syndrome and those with proteinuria. In this series, no evidence was found 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 in some patients. Two patients showed an almost identical picture initially and at re-biopsy 1 yr later. Persistent proteinuria was also a feature of the group as a whole. The pathological picture has similarities with that of idiopathic membranous glomerulopathy. The use of penicillamine in rheumatoid arthritis may induce persistent renal damage.