Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a series of 100 adult patients with definite rheumatoid arthritis of at most 3 years' duration and with no previous penicillamine, gold or systemic corticosteroid treatment, 50 patients were treated with D-penicillamine and 50 with gold for one yar. The dose of penicillamine was 600 mg daily. Sodium aurothiomalate was given 50 mg weekly up to a total of 13 mg/kg and thereafter 50 mg once a month. In both treatment groups a statistically significant decrease in the number of painful and/or swollen joints, an increase in haemoglobin and a decrease in ESR, serum ceruloplasmin-, alpha1-acid glycoprotein-, IgG-, IgM- and IgA levels was observed. All the changes in these clinical and laboratory tests were of the same degree in both treatment groups. In the penicillamine group 12 out of 20 seropositive patients became seronegative and in another 5 the Waaler-Rose titre dropped clearly. In the gold group, 7 out of 16 seropositive patients became seronegative, and the Waaler-Rose titre dropped in another 5. An equal increase in the number of eroded joints in hands and toes was seen in the penicillamine and the gold group. Penicillamine was discontinued because of side effects in 13 patients (26%), and gold treatment in 15 (30%). Proteinuria and/or haematuria were the most common causes of discontinuation in the penicillamine group.
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PMID:Comparison of penicillamine and gold treatment in early rheumatoid arthritis. 10 90

The nephrotic syndrome presumably caused by an immune complex glomerulonephritis constitutes a major side effect attendant upon chronic administration of penicillamine. The possible induction of an immune-complex glomerulonephritis by penicillamine and its further development after stopping the drug was investigated in rats. --60 rats were fed perorally 2000 mg D-Penicillamine/kg BW/die resp. for a period of 8--44 days. Following unilateral nephrectomy the animals were observed for further 5 weeks. --Dependent to the time of penicillamine application there was an increasing deposition of IgG and C3 in a granular pattern along the glomerular basement membrane and within the mesangium. The IgG deposits initially were focal and segmental later on diffuse and global in distribution. 5 weeks after stopping the penicillamine the immune globulin deposits had disappeared completely or at least in part as did the mild focal glomerulonephritis and the moderate proteinuria which developed in some animals after a 44 day treatment with penicillamine. --The results confirm the hitherto presumed immune complex pathogenesis of the penicillamine induced nephropathy. The disappearance of the immunoglobulins deposited and of proteinuria stopping penicillamine alludes the good prognosis of this kind of nephropathy.
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PMID:[Nephrotic syndrome presumable caused by an complex glomerulonephritis (author's transl)]. 14 Oct 75

In order to evaluate clinical efficacy of D-penicillamine (DP) a double-blind study was conducted by the Metalcaptase Research Group consisting of forty-one rheumatological centers in Japan. A total of 179 patients with rheumatoid arthritis (RA) was divided into two groups; one treated with 5 mg (control group) and the other with 100 mg (drug group) of DP in capsule form. The trial lasted 24 weeks. Global judgment by physicians revealed that improvement was found in 27% in the controls and 65% in the drug group. Adverse reactions occurred in 34% of the controls and 49% of the drug group. Skin rashes, taste disturbances, gastrointestinal upset and proteinuria were frequent in the drug group, but severe or fatal reactions could not be seen in this trial.
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PMID:Clinical evaluation of D-penicillamine by multicentric double-blind comparative study in chronic rheumatoid arthritis. 14 7

Characteristics of patients on penicillamine therapy for rheumatoid arthritis were correlated with the occurrence of different side-effects. Patients developing proteinuria tended to have lower sheep-cell agglutination test titres prior to therapy, but no other correlations were found. It is postulated that rheumatoid factor reacts with immune complexes, causing their precipitation and reducing renal glomerular deposition and therefore the incidence of proteinuria. Penicillamine would surely be the first choice of anti-rheumatic therapy if it were not for its side-effects. It is capable of controlling the disease, but in many cases treatment must be interrupted because of some potentially serious side-effects, such as thrombocytopenia, rash or nephropathy. Understanding the mode of action of a drug may lead to the development of new and better compounds. Similarly, understanding the mechanism of the side-effects may lead to their elimination. This survey was designed to identify factors which influenced the development of particular side-effects in patients receiving penicillamine for rheumatoid arthritis.
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PMID:Factors affecting the development of penicillamine side-effects. 31 May 74

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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PMID:Resumption of treatment with penicillamine after proteinuria. 48 79

There is much individual variation in the response of rheumatoid arthritis (RA) to penicillamine, some patients deriving benefit from very small doses. A dose of 750 mg daily is widely regarded as standard, and, while their RA commonly responds, many patients discontinue treatment because of adverse reactions to penicillamine. A more flexible prescribing policy might be more successful in the long term and was tested in 1 group of 20 patients, another receiving a 'standard' regimen, each beginning treatment at a low dose level. Of those who were given increases of dose only if response was poor 17 completed 1 year of treatment on an average maintenance dose of 308 mg daily, but only 11 of the other group on an average dose 613 mg daily. Proteinuria, which was found only in the latter group accounted for 6 withdrawals, all at doses of 625 mg daily or above. The reduction in rheumatoid activity appeared to be of about the same degree among the members of both groups who completed 12 months of treatment. Penicillamine should be given initially in a low dose and this should be raised only if there is lack of response after at least 4 weeks.
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PMID:Maintenance dose of penicillamine in rheumatoid arthritis: a comparison between a standard and a response-related flexible regimen. 51 42

In a 53-year-old woman an acute allergic thrombocytopenia (acute Werlhf's disease) occurred after treatment with D-penicillamine for one month which led to death. In two further patients transitory platelet deficiencies were observed after six and two months which regressed completely in six months and four weeks, respectively. One of the patients had nephrotic syndrome and a retrobulbar neuritis at the same time. Both symptoms were equally transitory and could not be demonstrated five weeks after cessation of therapy. In a further case a lethal Lyell syndrome developed three weeks after therapy was started. These observations show that during D-penicillamine treatment weekly, and later fornightly, blood counts should be performed. In the occurence of thrombocytopenia, leucopenia or anaemia treatments should be stopped; Signs of drug intolerance together with exanthemata should also led to a critical review of the indications and the dosage. D-Penicillamine should not be used when hypersensitivity to penicillin exists or when cell deficiencies have occurred after anti-reheumatic medication. The development of proteinuria should also result in withdrawal of the drug. Therapy with D-penicillamine requires conscientious follow-up urinalyses and blood counts as well as attention to allergic rashes.
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PMID:[Severe side-effects of treatment with D-penicillamine (author's transl)]. 117 64

This report includes 31 patients who developed a perimembranous glomerulonephritis generally 7 months after the onset of the treatment of various illnesses with D-Penicillamine. In all cases the patients had a proteinuria, associated with a hematuria in 12 cases. After the treatment was stopped 8 patients rapidly developed a nephrotic syndrome, while its onset was more gradual in 12 other patients. 5 patients initially with a nephrotic syndrome had no proteinuria at the time of a second biopsy made up to 12 months later. In these 5 cases the typical changes of perimembranous glomerulonephritis observed on electron microscopy were much reduced in the second biopsy.
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PMID:[Perimembranous glomerulonephritis after treatment with D-penicillamine. Report on 31 cases (author's transl)]. 119 63

Penicillamine has proved an effective second line agent in rheumatoid arthritis. Its use, however, is limited by its toxicity. Long term studies show that only between 30 and 40% of patients started on penicillamine are still taking the drug at 2 years. Toxicity is the chief reason for stopping treatment, the commonest adverse effects requiring cessation of therapy being proteinuria (10 to 13%), skin rashes (5 to 9%), gastrointestinal events (5%) and thrombocytopenia or leucopenia (2 to 5%). A number of autoimmune syndromes may rarely be induced by penicillamine. HLA-B8, Dr3 positive individuals and poor sulfoxidisers are at increased risk of developing toxicity. Meticulous supervision of penicillamine therapy is required to minimise toxicity.
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PMID:Penicillamine in rheumatoid arthritis. A problem of toxicity. 153 98

Localized scleroderma has no recognized internal organ involvement but may be disfiguring and disabling when the cutaneous lesions are extensive or affect children. There is no accepted or proven treatment for localized scleroderma. Case reports of 11 patients with severe, extensive localized scleroderma who were treated with D-penicillamine are summarized in this article. This drug was judged to have a favorable effect on the disease course in 7 (64%) of 11 patients. Improvement began within 3 to 6 months and consisted of cessation of active cutaneous lesions in all 7 patients, skin softening in 5, and more normal growth of the affected limb in 2 of 3 children. Joint stiffness and contractures also improved. The dose of D-penicillamine associated with a favorable response was as low as 2 to 5 mg/kg per day given over a period ranging from 15 to 53 months. D-Penicillamine caused nephrotic syndrome in 1 patient and milder reversible proteinuria in 3 other patients; none developed renal insufficiency. These data suggest that D-penicillamine may be effective in severe cases of localized scleroderma.
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PMID:D-penicillamine in the treatment of localized scleroderma. 218 97


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