Nephrotic syndrome penicillamine

Adverse effects are frequent. Patients may experience gastrointestinal upset, and dose-related impairment of taste is common. Thrombocytopenia is frequent but resolves when the drug is withdrawn unless it indicates the more serious aplastic anaemia which may also occur. Allergic reactions (rashes, fever) tend to occur during the early stages of treatment. Proteinuria, if it is heavy, is a reason for stopping penicillamine for it may herald the development of the nephrotic syndrome. 

Acute renal failure, e.g. cuninoglycosides, cisplatin Nephrotic syndrome, e.g. penicillamine, gold, cap-topril (only at higher doses than now recommended) Chronic renal failure, e.g. NSAIDs Functional impairment, i.e. reduced ability to dilute and concentrate urine (lithium), potassium loss in urine (loop diuretics), acid-base imbalance (acetazolamide). 

Hypersensitivity reactions are frequent early in a course of penicillamine, with urticarial or maculopapular rashes, fever, and lymphadenopathy. Cross-allergy to penicillin can occur. In addition, the use of penicillamine can be complicated by a unique variety of often serious autoimmune reactions, involving the skin, kidneys, liver, lungs, muscles, or other organs. Proteinuria is found in more than 10% of patients and sometimes develops into the nephrotic syndrome. Pemphigus, myasthenia gravis, polymyositis, or a lupus-like syndrome occur in smaller percentages. 

A patient with nephrotic syndrome that developed soon after the start of treatment with penicillamine has been described in detail (232). 

A 12-year-old boy with a history of a generalized pruritic rash after penicillin took penicillamine up to 500 mg/day for Wilson s disease. He had a rash after using penicillamine for 1 week. The penicillamine was stopped for 3 days. He developed nephrotic syndrome 2 weeks after restarting penicillamine. On electron microscopy, there was the typical picture of minimal change disease with extensive foot process effacement. 

Bindi P, Gilson B, Aymard B, Noel LH, Wieslander J. Antiglomerular basement membrane glomerulonephritis following D-penicillamine-associated nephrotic syndrome. Nephrol Dial Transplant 1997 12(2) 325-7. 

Siafakas CG, Jonas MM, Alexander S, Herrin J, Furuta GT. Early onset of nephrotic syndrome after treatment with D-penicillamine in a patient with Wilson s disease. Am J Gastroenterol 1998 93(12) 2544-6. 

Hallauer W, Gartner HV, Kronenberg KH, Manz G. Immunkomplexnephritis mit nephrotischem Syndrom unter Therapie mit D-PeniziUamin. [Immune complex nephritis with nephrotic syndrome following D-penicillamine therapy.] Schweiz Med Wochenschi" 1974 104(12) 434-8. 

In usual doses, 600-800 mg/day, pyritinol has a profile of adverse reactions reminiscent of that of penicillamine (2,3). Some 40% of users have adverse reactions, leading to withdrawal in about 23% of the total. The most common are non-specific rashes and stomatitis in addition, pemphigus, lichen planus, and photosensitivity have occurred. Gastrointestinal symptoms (diarrhea, gastral-gia, nausea, loss of taste) can occur, but are less frequent than with penicillamine. Thrombocytopenia, reversible extramembranous glomerulonephritis with nephrotic syndrome (4), a myasthenia-like picture, and acute polymyositis with positive rechallenge have also been described (5). 

Some degree of renal damage occurs in about 10% of patients taking tiopronin (1-3,5,6). As with penicillamine, proteinuria can progress to nephrotic syndrome (13,14). Biopsy may show minimal change membranous glomerulonephritis and granular depositions of IgG and C3 (13,15). 

In a comparison of tiopronin and penicillamine in the treatment of cystinuria in 15 children, nephrotic syndrome developed in one of the patients taking tiopronin no further details were given (16). 

Habib GS, Sallba W, Nashashibi M, Armali Z Penicillamine and nephrotic syndrome. Eur Intern Med 2006 17 343-8. PIrmohamed M Genetic factors in the predisposition to drug-induced hypersensitivity reactions. Aaps 2006 8 E20-6. 

Penicillamine 250-1,000 mg q. 24 hr 40% 100% Avoid Avoid Nephrotic syndrome One-third dose No data Dose for GFR 10-50 ml/min... 

Chelating agents, like all chemical compounds, exhibit toxic effects. These can arise from the fact that they increase the excretion of essential trace elements or from more subtle interactions. Thus all compounds which contain sulfhydryl compounds are capable of causing allergic reactions, such as the skin rash reported for DMSA (Grandjean et al. 1991), or the numerous problems which may arise from the continued administration of d-penicillamine such as nephrotic syndrome and anuria (Dubois et al. 1990). The administration of EDTA by itself may result in tetany due to the rapid drop in serum calcium which results, this being the reason for its customary administration as the calcium complex. 

Farallo M, Amoruso C, Frattini C, Ardissino G, Nebbia G. Nephrotic syndrome after treatment with d-penicillamine in a pediatric patient with Wilson s disease. Pediatr Med Chir Sep-Oct 2012 34(5) 234-6. 

In a further publication Gartner et al. review 31 cases of perimembranous glomerulonephritis attributed to penicillamine (12 ). In addition to proteinaemia, 12 patients had haematuria. In 20 patients a nephrotic syndrome had developed 5 patients had a transitory impaired renal function. It is concluded that penicillamine-induced nephritis probably has a better prognosis than idiopathic perimembranous glomerulonephritis. 

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