Pharmacovigilance study of anti-infective-related acute kidney injury using the Japanese adverse drug event report database

• Published in: BMC pharmacology & toxicology Vol. 22; no. 1; p. 47
• Main Authors: Nakao, Satoshi, Hasegawa, Shiori, Umetsu, Ryogo, Shimada, Kazuyo, Mukai, Ririka, Tanaka, Mizuki, Matsumoto, Kiyoka, Yoshida, Yu, Inoue, Misaki, Satake, Riko, Nishibata, Yuri, Liao, Jun, Nakamura, Mitsuhiro
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 30.08.2021; BioMed Central; BMC
• Subjects: Acute kidney injury; Acute Kidney Injury - chemically induced; Adult; Adverse Drug Reaction Reporting Systems; Aged; Aged, 80 and over; Analysis; Anti-infective; Anti-Infective Agents - adverse effects; Antibiotics; Antiinfectives and antibacterials; Carbapenems; Cephalosporins; Dictionaries; Drug Therapy, Combination; Drugs; Evaluation; Female; Fluoroquinolones; Glycopeptides; Health aspects; Health care; Humans; JADER; Japan; Japanese adverse drug event report database; Kidneys; Male; Mathematical analysis; Middle Aged; Morbidity; Mortality; Odds Ratio; Patients; Pharmacovigilance; Polypharmacy; Propensity score; Sepsis; Tazobactam; Therapy; Young Adult; Japan; United States > US; Japanese adverse drug event report database; Polypharmacy; Propensity score; Anti-infective; JADER; Acute kidney injury
• ISSN: 2050-6511; 2050-6511
• DOI: 10.1186/s40360-021-00513-x

Acute kidney injury (AKI) is associated with significant increases in short- and long-term morbidity and mortality. Drug-induced AKI is a major concern in the present healthcare system. Our spontaneous reporting system (SRS) analysis assessed links between AKI, along with patients' age, as healthcare-associated risks and administered anti-infectives. We also generated anti-infective-related AKI-onset profiles. We calculated reporting odds ratios (RORs) for reports of anti-infective-related AKI (per Medical Dictionary for Regulatory Activities) in the Japanese Adverse Drug Event Report database and evaluated the effect of anti-infective combination therapy. The background factors of cases with anti-infective monotherapy and combination therapy (≥ 2 anti-infectives) were matched using propensity score. We evaluated time-to-onset data and hazard types using the Weibull parameter. Among 534,688 reports (submission period: April 2004-June 2018), there were 21,727 AKI events. The reported number of AKI associated with glycopeptide antibacterials, fluoroquinolones, third-generation cephalosporins, triazole derivatives, and carbapenems were 596, 494, 341, 315, and 313, respectively. Crude RORs of anti-infective-related AKI increased among older patients and were higher in anti-infective combination therapies [anti-infectives, ≥ 2; ROR, 1.94 (1.80-2.09)] than in monotherapies [ROR, 1.29 (1.22-1.36)]. After propensity score matching, the adjusted RORs of anti-infective monotherapy and combination therapy (≥ 2 anti-infectives) were 0.67 (0.58-0.77) and 1.49 (1.29-1.71), respectively. Moreover, 48.1% of AKI occurred within 5 days (median, 5.0 days) of anti-infective therapy initiation. RORs derived from our new SRS analysis indicate potential AKI risks and number of administered anti-infectives.