Effect of Penicillamine on the Kidney

Davison, A. M.; Day, A T; Golding, J.; Thomson, David

doi:10.1177/00359157770700s334

Cited by 10 publications

(4 citation statements)

References 17 publications

(14 reference statements)

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“…[4][5][6][7] Although in a few patients proteinuria increased for up to seven months after penicillamine was stopped, it peaked within three months in 82% of the patients and caused the nephrotic syndrome in 64% confirming previous reports.48 There is general agreement that proteinuria gradually decreases when penicillamine treatment is stopped.49 In three previous series in which patients were followed up for 12 months or longer, however, continuing proteinuria (0 4-1 7 g/24 h) was observed in 25-63% of cases and caused concern that a progressive renal lesion may develop in some cases. 489 We found that 40% of patients continued to have appreciable proteinuria (median 0-5 g/24 h, range 0-4-1-4 g/24 h) 12 months after stopping treatment.…”

Section: Discussionmentioning

confidence: 99%

Natural course of penicillamine nephropathy: a long term study of 33 patients

Hall¹,

Jawad²,

Harrison³

et al. 1988

BMJ

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To elucidate the natural course of the nephropathy associated with penicillamine and thereby facilitate its clinical management 33 patients with rheumatoid arthritis who developed proteinuria during treatment with oral penicillamine were studied in detail throughout their renal illness. Renal biopsies were performed, and creatinine clearance and proteinuria were measured serially for 74 months (range 16-148 months). Fourteen patients developed proteinuria within six months after the start of treatment and 27 within 12 months. When treatment was stopped the proteinuria reached a median peak of 4*2 g/24 h (range 0-3-15-0 g/24 h) at one month (range 0-7 months) before resolving spontaneously by six months (12 patients), 12 months (21), or 18 months (29). In ali patients but one, who developed carcinoma of the renal pelvis, proteinuria resolved by 21 months and its median duration was eight months. The median first and last measurements of creatinine clearance showed no appreciable change (80 ml/min and 78 ml/min), and no patient died from or needed treatment for renal failure. The HLA-B8 or HLA-DR3 alloantigen, or both, were identified in 10 patients. Renal biopsy specimens showed membranous glomerulonephritis in 29 patients, minimal change nephropathy in two, and electron dense deposits in the mesangial regions in two.In all the patients whose nephropathy was due solely to treatment with penicillamine the proteinuria resolved completely

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Section: Discussionmentioning

confidence: 99%

Natural course of penicillamine nephropathy: a long term study of 33 patients

Hall¹,

Jawad²,

Harrison³

et al. 1988

BMJ

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“…D(-)-Penicillamine [D(-)-/fl,-dimethylcysteine] has been used as an anti-rheumatic agent, but its mechanism of action is not clearly established, although reduction of disulphide bridges in Rheumatoid Factor (Wernick et al, 1983) and inhibition of collagen cross-linking (Nimni et al, 1972) have been suggested. One major problem with penicillamine as an anti-rheumatic drug is that there is a high incidence of patients suffering adverse side effects, which include problems in clearance of immune complexes with resulting proteinuria and glomerulonephritis (Andrews et al, 1973;Davison et al, 1977;Kean et al, 1980). Drugs that induce this type of side effect have been shown to inhibit complement component C4 (Sim et al, 1984).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of the covalent binding reaction of complement component C4 by penicillamine, an anti-rheumatic agent

Sim

Dodds

Goldin

1989

Biochemical Journal

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D(-)-Penicillamine [D(-)-beta beta-dimethylcysteine] is an anti-arthritic drug, but its use is limited by adverse side effects, which include problems in immune-complex clearance. Complement is important as a source of inflammatory mediators in rheumatoid arthritis and is also involved in immune-complex clearance. Thus inhibition of the complement cascade would be likely to contribute to both the therapeutic and the toxic effects of penicillamine. It is shown that penicillamine and cysteine are potent inhibitors of the covalent binding of activated complement component C4 to immune complexes. [35S]Cysteine itself becomes covalently bound to C4b through the thioester site. Penicillamine and cysteine are more reactive with the C4A isotype than with the C4B isotype of the HLA class III protein C4. The limited amino acid sequence differences between C4A and C4B include a cysteine/serine interchange, and it is suggested that the cysteine residue in C4A contributes to the increased rate of reaction of C4A with the alpha-amino-beta-thiol compounds.

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“…All 5 patients have passed this high risk time without recurrence of proteinuria. Proteinuria, though rare after 12 months of treatment (Hill, 1977), may occur at wide ranges of dose and length of treatment (Davison et al, 1977). Urinary FDP excretion correlates with intraglomerular fibrin deposition (Davison et al, 1973) and this relates to the severity of the glomerular inflammation and may be a more sensitive indicator of glomerular disease.…”

Section: Discussionmentioning

confidence: 99%

Resumption of treatment with penicillamine after proteinuria.

Hill¹,

Hill²,

Davison³

1979

Annals of the Rheumatic Diseases

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SUMMARY Penicillamine has been successfully reintroduced and continued for a minimum of 13 months in 5 patients who developed proteinuria during the first course of the drug. The daily maintenance dose during the second course was 150-250 mg taken midway between 2 meals. Proteinuria did not recur; no significant excretion of fibrin degradation products occurred; complement, urea, creatinine, and serum albumin remained within normal limits. Urine microscopy showed no abnormality.

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Effect of Penicillamine on the Kidney

Cited by 10 publications

References 17 publications

Natural course of penicillamine nephropathy: a long term study of 33 patients

Natural course of penicillamine nephropathy: a long term study of 33 patients

Inhibition of the covalent binding reaction of complement component C4 by penicillamine, an anti-rheumatic agent

Resumption of treatment with penicillamine after proteinuria.

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