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Cimetidine-induced tubulointerstitial nephritis with both MPO-ANCA and PR3-ANCA
Hideki Ueda1,2, Eiji Ishimura3, Takayuki Yunoki4
1Department of Nephrology, Osaka City University Graduate School of Medicine, Osaka, Japan. uhideki@skyblue.ocn.ne.jp.
Abstract:
We describe a 75-year-old man with tubulointerstitial nephritis (TIN) with myeloperoxidase (MPO)-antineutrophil antibody (ANCA) and proteinase-3 (PR3)-ANCA. He had a slight fever and eruption with itching after taking cimetidine (prescribed after gastrectomy for gastric cancer) and he was admitted to a nearby hospital. There, he showed proteinuria, serum creatinine (sCr) of 2.9 mg/dl, and creatinine clearance (Ccr) of 44 ml/min per 1.73 m2. His MPO-ANCA titer was 267 EU, and PR3-ANCA titer was 112 EU. Abnormal concentrations in bilateral kidneys were found by gallium scintigraphy. For these reasons, he was transferred to our hospital. Percutaneous renal biopsy was performed after admission. Severe tubular atrophy, mild interstitial fibrosis, and severe mononuclear cell infiltration of the interstitium were noted. Drug-induced renal impairment was suspected, and cimetidine administration was withdrawn. Lymphocyte stimulation tests (DLSTs) were performed. The cimetidine titer was positive, at 2,537 cpm. After the withdrawal of cimetidine, the PR3-ANCA titer was reduced gradually, and, next, the MPO-ANCA titer was also reduced. The sCr level was reduced to 1.2 mg/dl. In summary, we report herein the first case of cimetidine-induced TIN associated with both MPO-ANCA and PR3-ANCA.
Insights
This study reports the first case of drug-induced tubulointerstitial nephritis (TIN) caused by cimetidine, which was associated with both myeloperoxidase (MPO)-antineutrophil antibody (ANCA) and proteinase-3 (PR3)-ANCA.
Area of Science:
- Nephrology
- Immunology
- Pharmacology
Background:
- Tubulointerstitial nephritis (TIN) is a kidney disease characterized by inflammation and damage to the tubules and interstitium.
- Antineutrophil antibody (ANCA)-associated vasculitis (AAV) can affect the kidneys, leading to various forms of glomerulonephritis and interstitial nephritis.
- Cimetidine, a histamine H2 receptor antagonist, is commonly used to treat acid-related gastrointestinal disorders.
Observation:
- A 75-year-old man developed fever, itching, rash, proteinuria, and acute kidney injury (serum creatinine 2.9 mg/dl) after starting cimetidine.
- Elevated titers of myeloperoxidase (MPO)-ANCA and proteinase-3 (PR3)-ANCA were detected, along with abnormal kidney uptake on gallium scintigraphy.
- Renal biopsy revealed severe tubular atrophy, interstitial fibrosis, and mononuclear cell infiltration, consistent with drug-induced interstitial nephritis.
Findings:
- Drug-induced renal impairment was suspected, and cimetidine was discontinued.
- Lymphocyte stimulation tests confirmed cimetidine hypersensitivity (positive DLST).
- Following cimetidine withdrawal, PR3-ANCA and MPO-ANCA titers decreased, and renal function improved (serum creatinine to 1.2 mg/dl).
Implications:
- This case highlights cimetidine as a potential cause of TIN with a unique dual MPO-ANCA and PR3-ANCA profile.
- It underscores the importance of considering drug-induced causes in patients presenting with ANCA-associated TIN.
- Early recognition and withdrawal of the offending drug are crucial for managing drug-induced TIN and improving renal outcomes.
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