Immunopathological study of bucillamine induced nephropathy in patients with rheumatoid arthritis

Bucillamine is a compound of tiopronin which has anti-rheumatic action pharmacologically based on the similar chemical structure of D-penicillamine. We studied the clinical profile and the precise histological and immunological changes in kidney tissue in five patients with rheumatoid arthritis (RA) who had the profound proteinuria along with the bucillamine (BU) therapy. There was no specific predisposition for BU-induced proteinuria in clinical profiles of five RA patients as age, disease duration, disease activity and co-given drugs except that all of patients were female. Urinalysis revealed proteinuria in all 5 patients (2 patients : nephrotic syndrome) and microscopic hematuria in 4 out of 5 of patients. Renal failure was not observed in all patients. The renal biopsy was performed in 4 patients. The histological findings by light microscopy, fluorescent antibody technique and electron microscopy demonstrated membranous glomerulonephritis (MGN), i.e. positive staining of IgG and electron dense subepithelial deposits in glomerular basement membrane (GBM). Nevertheless, the number of subepithelial deposits in GBM was smaller and the location was scattered compared with idiopathic MGN. The total dosis of BU administration in these patients varied from 7.9 g to 128 g (average : 41.6 g). The causes of BU-induced nephropathy were not known. DLST by BU was, however, positive in 2 out of 5 patients. The outcome of BU-induced proteinuria seemed to be good since one of the patients had the renal failure and the amount of proteinuria was decreased or disappeared by steroid therapy or discontinuation of BU. Thus, the abnormal responses of cellular immunity to this drug might involve in the development of BU-nephropathy.