Causality assessment · Causality: well established

Penicillamine and Proteinuria / membranous nephropathy: is the FAERS signal real?

n=65 co-reports · PRR 78.6 · ROR 84.5

Penicillamine side-effect profile All assessments See in the full list

A written Bradford Hill assessment of one drug–event pair. The grade is a judgement about the signal, not a statement that this drug causes this event in any one person; FAERS counts are reports, not rates.

Causality: well established

Penicillamine ↔ Proteinuria / membranous nephropathy

n=65 co-reports · PRR 78.6 · ROR 84.5

Penicillamine, used in Wilson's disease, cystinuria, and historically in rheumatoid arthritis, is a well-recognised cause of membranous nephropathy presenting as proteinuria, sometimes progressing to nephrotic syndrome. The effect is dose-related, usually emerges after months of therapy, and frequently improves when the drug is stopped. The 65 FAERS co-reports (PRR 78.6) are dominated by proteinuria rather than overt nephrotic syndrome because routine urinalysis during penicillamine therapy catches it early; the mechanism is thought to involve immune-complex deposition in the glomerulus.

Regulatory basis: penicillamine prescribing information (proteinuria; routine urinalysis monitoring). Established penicillamine membranous-nephropathy literature.

Bradford Hill viewpoint	Status	Note
Temporality (necessary)	met	Proteinuria develops after months of exposure and often improves after withdrawal
Strength	partial	PRR 79 on a small co-report count — a large relative signal on small absolute numbers
Consistency	met	Reproduced across decades of penicillamine-nephropathy case series
Specificity	met	Membranous nephropathy is a fairly distinctive drug-related pattern
Biological gradient	met	Dose-related; risk rises with higher cumulative exposure
Plausibility	met	Immune-complex deposition in the glomerulus is the proposed mechanism
Coherence	met	Coheres with routine urinalysis monitoring during penicillamine therapy
Experiment	partial	Dechallenge (withdrawal) frequently reduces proteinuria; no randomized trial
Analogy	met	Analogous to gold-salt-induced membranous nephropathy

This page's own qualitative read, not an automated/citation-gated assessment.

Not searched in ClinicalTrials.gov. Penicillamine trials are old and rarely post results to ClinicalTrials.gov, and proteinuria here is a monitored laboratory effect rather than a coded trial endpoint.