Penicillamine Induced Membranous Glomerulonephritis

Abstract

Renal biopsy material from thirty-five patients, who developed glomerulonephritis whilst receiving penicillamine, was studied. All patients had a membranous glomerulonephritis diagnosed either on 0.5 μ silver stained sections or by electron microscopy and occasionally confirmed by immunofluorescence. In 16 cases light microscopy alone of conventional 3 μ sections showed only a minimal change lesion. Clinical information and follow-up data show that as in idiopathic membranous glomerulonephritis the condition may present as persistent proteinuria, proteinuria going on to a nephrotic syndrome, or as an acute nephrotic syndrome. Proteinuria occurred 1-24 months after penicillamine was started with a median time of 7 months, and was unrelated to the amoung of pinicillamine given. Daily doses of 900-1800 mg/day of penicillamine were given. In 33 cases penicillamine was stopped within 3 months of proteinuria being first noted. The magnitude of the proteinuria may not reach a peak for 2-4 months after being noted, but then usually falls rapidly over the next two months to less than 2 d/day. After stopping penicillamine the proteinuria may disappear within two months and is usually less than 0.3 g'day (‘trace proteinuria’) within 12 months. Drug induced membranous glomerulonephritis affords a unique opportunity to study the natural history of the early stages of membranous glomerulonephritis. We have observed that the deposits laid down on the epithelial side of the glomerular basement membrane appear to be slowly covered and later incorporated into the basement membrane by new basement membrane like material apparently formed by the covering epithelial cells. With time the deposits become fainter and move towards the endothelial side of the basement membrane suggesting a continual turnover of the basement membrane, being produced from the epithelial cells and removed by endothelial and possibly mesangial cells.