Acute Interstitial Nephritis Secondary to Metamizole; The Rise of Drug Tourism 

V Sandys, D Byrne

Department of Medicine, St James’s Hospital, James’s St, Dublin 8

Sir,

People are increasingly turning to the internet to source medications. The safety, viability and security of this approach poses many risks and is open to question. We report on acute tubulointerstitial nephritis (ATIN) secondary to metamizole, a medication banned in Ireland, but readily available in some European countries. Renal toxicity secondary to metamizole is becoming increasingly recognised1-3, but to our knowledge, has yet to be included in a meta-analysis of the drugs adverse effect profile4.

A 38-year-old Brazilian woman presented with a 2/52 history of occipital headache, and a 1/52 history of dizziness, epigastric pain, nausea and anorexia. Physical exam showed BP 130/81; afebrile, no rash, synovitis, oedema. Urinalysis revealed 2 + protein and 1 + blood. On admission her creatinine was 452, urea 16.5, Hb 8.2. Venous pH was 7.33 with a HCO3 of 21, PCO2 6.31. WCC count 14.2, Neutrophils 11.3, CRP 85.3. Eosinophils were normal at 0.3. ANA was positive at 1:80, ENA was negative. Urinalysis revealed a protein count of 0.26. US abdomen noted enlargement of the kidneys suggestive of renal parenchymal disease. Following review by nephrology, she admitted to taking neosaldina; a combination of metamizole, caffeine, and isometheptene mucate, which she had purchased online. Her renal function plateaued at a creatinine of 527, despite drug withdrawal. Renal biopsy subsequently showed extensive lymphocytic tubulitis with tubule destruction and accumulation of eosinophils, neutrophils and a diffuse interstitial inflammatory infiltrate. A diagnosis of acute diffuse interstitial nephritis was made. The patient was treated with oral prednisolone 50 mg 6 days post admission, septrin 960 mg M/W/F, and IV venofer, and was discharged after 11 days. Serum creatinine decreased from 507 to 153 following 19 days of treatment with steroids.

Metamizole is an ampyrone sulfonate analgesic and antipyretic that belongs to the non-steroidal analgesic class. Its use has been banned since 1974 in more than 30 countries given the potential for severe, and controversial side effects such as agranulocytosis and aplastic anaemia2. Renal side effects of metamizole are becoming increasingly acknowledged, with several cases of acute kidney injury (AKI) being reported to date1-3. One study has noted an incidence of 10.48 per 10,000 cases of ATIN, higher than the equivalent incidence for traditional NSAIDs, including ibuprofen and diclofenac2. The aetiology of metamizole-induced ATIN is thought to be hypersensitivity based, but, in contrast to NSAIDS, symptoms typically occur within 24 hours to a few days of therapy3. As with previous cases, our patient lacked systemic signs of allergy, eosinophilia, or significant proteinuria3. Her renal biopsy was consistent with a hypersensitivity aetiology, with diffuse interstitial infiltrates and eosinophilia. Her symptoms did not resolve following withdrawal from the medication, however, which differs from the majority of cases of metamizole ATIN at normal pharmacological doses2,3. Typically, AKI secondary to metamizole can be treated conservatively3, with isolated incidents to date requiring steroid therapy and/ or haemodialysis1,3.

Given the ready availability of metamizole online and overseas, we urge that a thorough evaluation of its renal effects be undertaken.

References

1. Garcia, Montserrat, Ramón Saracho, Nekane Jaio, Kalliopi Vrotsoukanari, and Carmelo Aguirre. 2010. Inadequate drug prescription and the rise in drug-induced acute tubulointerstitial nephritis incidence. NDT plus 3, no. 6: 555-557.

2. Hassan Kamal, Khalid Khazim, Fadi Hassan, and Shadi Hassan. 2011. Acute kidney injury associated with metamizole sodium ingestion. Renal failure, no. 0: 544-547.

3. Valeria Berruti, Gennaro Salvidio, Stefano Saffioti, Roberto Pontremoli, Olga Arnone,Massimo Giannoni and Giacomo Garibotto. 1998. Noramidopyrine (Metamizol) and acute interstitial nephritis. Nephro Dial Transplant 13: 2110-2112

4. Thomas Kötter Bruno R. da Costa, Margrit Fässler, Eva Blozik, Klaus Linde, Peter Jüni, Stephan Reichenbach, and Martin Scherer. 2015. Metamizole-associated adverse events: a systematic review and meta-analysis. PloS One 10, no. 4.

p445