Facing the Challenge of Drug-Induced Acute Interstitial Nephritis

Background: Acute interstitial nephritis (AIN) is one of the chief causes of acute kidney injury (AKI). AIN might be produced by drugs, infections, autoimmune diseases, or can be idiopathic. Among these etiologies, drug-induced AIN (DI-AIN) is the dominant one in many countries. Even when DI-AIN is suspected, identification of the putative drug is challenging. Summary: DI-AIN is an increasingly common cause of AKI. Diagnosis continues to pose a challenge for physicians due to nonspecific clinical symptoms, and the fact that it can be triggered by a wide variety of medications. Furthermore, the gold standard for the diagnosis is kidney biopsy. All these aspects render the diagnosis more difficult. The withdrawal of the causative drug of DI-AIN is the centerpiece of the treatment, and if early restoration of original kidney function is not obtained, several studies support the treatment with steroids especially when they are started quickly. Key Messages: Almost all drugs have the potential to produce drug-induced acute interstitial nephritis (DI-AIN); however, antibiotics, nonsteroidal anti-inflammatory agents, and proton pump inhibitors account for the majority of the reported cases. DI-AIN is produced by an idiosyncratic delayed type IV hypersensitivity reaction, but the precise pathophysiological mechanism remains to be elucidated. DI-AIN symptoms are nonspecific, and most of the patients will present mild symptoms including malaise, nausea, and vomiting. The classical triad, associating fever, rash, and eosinophilia, is seldom present. Nonoliguric acute kidney injury is the main renal manifestation of DI-AIN. Tubular nonnephrotic range proteinuria is usually present. Diagnosis of DI-AIN relies on maintaining a high index of suspicion in those patients at greater risk, but kidney biopsy is required to confirm diagnosis. Histologically, AIN is characterized by the presence of an extensive interstitial infiltrate, mainly composed of lymphocytes and monocytes, but eosinophils, plasma cells, histiocytes, and polymorphonuclear cells can also be found. The withdrawal of the presumed causative drug of DI-AIN is the mainstay of the treatment. When there is no evidence of kidney function recovery after an interval of 5-7 days since interrupting the treatment with the suspected drug, several studies support the treatment with steroids, especially when they are promptly started. Early corticosteroids would decrease the inflammatory infiltrates of the kidney interstitium, thus preventing the risk of subsequent fibrosis.