Cyril Leven1, Laurent Hudier1, Sylvie Picard2, Hélène Longuet3, Nolwenn Lorcy4, Gérard Cam1, Zakaria Boukerroucha5, Thibault Dolley-Hitze6, Philippe Le Cacheux7, Jean-Michel Halimi3, Emilie Cornec Le Gall8, Catherine Hanrotel-Saliou8, Audrey Arreule9, Michel Massad10, Agnès Duveau11, Grégoire Couvrat-Desvergnes12, Eric Renaudineau13. 1. Hôpital Broussais, service de néphrologie, 35400 Saint-Malo, France. 2. Centre hospitalier universitaire de Rennes, service de pharmacovigilance, 35033 Rennes cedex 9, France. 3. Hôpital Bretonneau, service de néphrologie, 37000 Tours, France. 4. Centre hospitalier universitaire de Rennes, service de néphrologie, 35033 Rennes cedex 9, France. 5. Centre hospitalier universitaire de Poitiers, service de néphrologie, 86021 Poitiers, France. 6. Centre AUB santé, 35400 Saint-Malo, France. 7. Hôpital Yves Le Foll, service de néphrologie, 22000 Saint-Brieuc, France. 8. Hôpital de la Cavale Blanche, service de néphrologie, 29609 Brest, France. 9. Hôpital de Girac, service de néphrologie, 16959 Angoulême, France. 10. Hôpital Centre Bretagne, service de néphrologie, 56920 Noyal-Pontivy, France. 11. Hôpital du Mans, service de néphrologie, 72000 Le Mans, France. 12. Centre hospitalier universitaire de Nantes, service de néphrologie, 44000 Nantes, France. 13. Hôpital Broussais, service de néphrologie, 35400 Saint-Malo, France. Electronic address: e.renaudineau@ch-stmalo.fr.
Abstract
OBJECTIVE: Certain medications have been associated with drug-induced acute interstitial nephritis (AIN), but few prospective studies have been published. This prospective observational study aims to record and assess incidents of drug-induced AIN observed over a period of one year in nephrology units in France. The goal is to determine which medications are involved in AIN and to expound the clinical and biological presentation, management, and evolution of AIN. METHODS: Between April 2012 and April 2013, drug-associated cases of AIN were prospectively recorded in 24 patients registered in 11 nephrology units that belong to the Société de Néphrologie de l'Ouest (SNO). Data sheets, including suspected and concomitant drug(s), kidney function assessment, biological disturbances, clinical signs, histological data, management, and evolution, were collected by the Rennes Regional Pharmacovigilance Center and recorded in the French pharmacovigilance database. RESULTS: In order, the most frequently involved medications in the AIN cases were: vitamin K antagonists (33.3% of the cases, almost exclusively fluindione), antibiotics (20.8% of cases) non-steroidal anti-inflammatory drugs (20.8% of cases), and proton pump inhibitors (16.7% of cases). The mean delay of onset to AIN was 8.3 weeks. At the time of diagnosis, mean serum creatinine was 366 μM, higher for vitamin K antagonists (VKAs), except in the case of warfarin. During the course of an AIN event, 70% of patients had complete blood count and/or urine analysis abnormalities, 55% had clinical signs of systemic hypersensitivity, and 13% of patients had hepatic disorders. Renal biopsies were performed in 54% of patients; however, only 37% of patients requiring therapeutic anticoagulation underwent a biopsy. Suspected drugs were discontinued in all patients and the majority was treated with oral corticosteroids. Renal function often continued to be impaired after an AIN event. At baseline, 25% of patients had chronic kidney disease (CKD); after an AIN event, 67% of patients were noted to have CKD. CONCLUSION: Physicians need to be aware of the possibility of drug-induced acute interstitial nephritis as a common cause of acute kidney injury (AKI). This study supports increased vigilance when prescribing three therapeutic classes frequently associated with AIN: antibiotics, NSAIDs and PPIs (especially in instances of polypharmacy), which were associated with two thirds of the AIN cases in this study. Fluindione, an oral anticoagulant exclusively marketed in Luxembourg and France where it constitutes the vast majority of VKA prescriptions, was associated with one third of the AIN cases alone, making it a common possible culprit of drug-induced AIN, warranting particular attention.
OBJECTIVE: Certain medications have been associated with drug-induced acute interstitial nephritis (AIN), but few prospective studies have been published. This prospective observational study aims to record and assess incidents of drug-induced AIN observed over a period of one year in nephrology units in France. The goal is to determine which medications are involved in AIN and to expound the clinical and biological presentation, management, and evolution of AIN. METHODS: Between April 2012 and April 2013, drug-associated cases of AIN were prospectively recorded in 24 patients registered in 11 nephrology units that belong to the Société de Néphrologie de l'Ouest (SNO). Data sheets, including suspected and concomitant drug(s), kidney function assessment, biological disturbances, clinical signs, histological data, management, and evolution, were collected by the Rennes Regional Pharmacovigilance Center and recorded in the French pharmacovigilance database. RESULTS: In order, the most frequently involved medications in the AIN cases were: vitamin K antagonists (33.3% of the cases, almost exclusively fluindione), antibiotics (20.8% of cases) non-steroidal anti-inflammatory drugs (20.8% of cases), and proton pump inhibitors (16.7% of cases). The mean delay of onset to AIN was 8.3 weeks. At the time of diagnosis, mean serum creatinine was 366 μM, higher for vitamin K antagonists (VKAs), except in the case of warfarin. During the course of an AIN event, 70% of patients had complete blood count and/or urine analysis abnormalities, 55% had clinical signs of systemic hypersensitivity, and 13% of patients had hepatic disorders. Renal biopsies were performed in 54% of patients; however, only 37% of patients requiring therapeutic anticoagulation underwent a biopsy. Suspected drugs were discontinued in all patients and the majority was treated with oral corticosteroids. Renal function often continued to be impaired after an AIN event. At baseline, 25% of patients had chronic kidney disease (CKD); after an AIN event, 67% of patients were noted to have CKD. CONCLUSION: Physicians need to be aware of the possibility of drug-induced acute interstitial nephritis as a common cause of acute kidney injury (AKI). This study supports increased vigilance when prescribing three therapeutic classes frequently associated with AIN: antibiotics, NSAIDs and PPIs (especially in instances of polypharmacy), which were associated with two thirds of the AIN cases in this study. Fluindione, an oral anticoagulant exclusively marketed in Luxembourg and France where it constitutes the vast majority of VKA prescriptions, was associated with one third of the AIN cases alone, making it a common possible culprit of drug-induced AIN, warranting particular attention.