Fluoroquinolones and the Risk of Acute Kidney Injury
Abstract & Commentary
By Rahul Gupta, MD, MPH, FACP, Clinical Assistant Professor, West Virginia University School of Medicine, Charleston, WV. Dr. Gupta reports no financial relationships relevant to this field of study.
This article originally appeared in the September 15, 2013, issue of Internal Medicine Alert. It was edited by Stephen Brunton, MD, and peer reviewed by Gerald Roberts, MD. Dr. Brunton is Adjunct Clinical Professor, University of North Carolina, Chapel Hill, and Dr. Roberts is Senior Attending Physician, Long Island Jewish Medical Center, NS/LIJ Health Care System, New Hyde Park, NY. Dr. Brunton serves on the advisory board for Abbott, Amarin, Boehringer Ingelheim, Duchesnay, Janssen, Lilly, Novo Nordisk, Sunovion, and Teva; he serves on the speakers bureau of Boehringer Ingelheim, Janssen, Lilly, Novo Nordisk, and Teva. Dr. Roberts reports no financial relationship to this field of study.
Synopsis: In men taking oral fluoroquinolone antibiotics, the risk of acute renal failure is doubled, and when combined with renin-angiotensin-system blockers, the risk increases by 4.5 fold.
Source: Bird ST, et al. Risk of acute kidney injury associated with the use of fluoroquinolones. CMAJ 2013;185:E475-E482.
Fluoroquinolones are commonly prescribed bactericidal agents with a wide spectrum of activity. In addition to the coverage against conventional gram-negative organisms, newer agents in this class have an expanded spectrum of activity against a variety of gram-positive and atypical organisms. One agent, moxifloxacin, even has increased activity against anaerobic bacteria. Additionally, fluoroquinolones are a promising new class of drugs for the treatment of tuberculosis.1 Fluoroquinolones are also associated with a variety of known adverse effects. These include gastrointestinal, neurological, dermatological, respiratory, and cardiovascular effects. Similar to other antimicrobials, it is not uncommon to observe newer side effects with more extensive clinical use after regulatory approval. Case reports of tendon rupture and retinal detachment have indicated that these drugs may damage collagen and connective tissue.2 Similarly, reports of acute kidney injury with the use of fluoroquinolones have been published, and it is often included in the product label in the list of potential, but uncommon, adverse reactions.3 Since acute kidney injury is serious and potentially a fatal adverse event, it is essential that we attempt to quantify this risk.
In their study, Bird et al analyzed a Health Plan Claims Database that contained fully adjudicated medical and pharmacy claims for more than 68 million patients from U.S. health care plans. A nested case-control design of men aged 40-85 years between 2001 and 2011 was used for primary analysis. Data were extracted for 2 million men who had both prescription and medical coverage. Those men who met the inclusion criteria between January 1, 2001, and June 30, 2011, and who had 365 days of enrollment with no acute kidney injury were included. Men with a history of chronic kidney disease or dialysis were excluded since they may be more prone to acute kidney injury. Cases were defined as those admitted to hospital for acute kidney injury, and controls were admitted to hospital with a different presenting diagnosis. Drug exposure to oral fluoroquinolones such as ciprofloxacin, gatifloxacin, gemifloxacin, levofloxacin, moxifloxacin, and norfloxacin was included. Ophthalmic, topical, and intravenous fluoroquinolones were excluded as the study was focused on outpatient-dispensed preparations with significant systemic absorption. Current use was defined as having a supply of or stopped taking a fluoroquinolone within a week of hospitalization. Recent users were those who had a prescription termination up to 60 days before admission and no drug taken within the week prior to admission. Past users had a prescription termination 61-180 days prior to admission and had no active prescriptions during days 0-60.
Researchers found that current fluoroquinolone use was associated with a 2.18 fold (95% confidence interval [CI] 1.74-2.73) higher adjusted relative risk (RR) of acute kidney injury compared with no use. The study researchers did not find any association between acute kidney injury and recent or past fluoroquinolone use. The researchers observed one additional case per 1529 patients given fluoroquinolones. Additionally, the dual use of fluoroquinolones and renin-angiotensin-system blockers was associated with a 4.46 fold (95% CI, 2.84-6.99) higher adjusted RR for acute kidney injury. The use of amoxicillin or azithromycin was not associated with acute kidney injury.
The limitations of this study included a lack of information on kidney injury severity, an inability to assess the risk associated with the dosage or duration of treatment, and residual confounding inherent in observational research.
Commentary
There is no doubt that when serious infections occur, a variety of wide-spectrum antibiotics, including fluoroquinolones, are appropriate and required to be prescribed in order to save lives. However, this study finds more than a two-fold increased risk of acute kidney injury requiring hospital admission with the use of fluoroquinolone antibiotics among adult men. In clinical practice, when oral fluoroquinolones are prescribed, the potential for acute kidney injury is generally not a clinical consideration. However, the study results mean that physicians need to be aware of the risks of acute kidney injury when prescribing these drugs, albeit much lower in prevalence. Additionally, it is also a concern that a strong interaction with concurrent use of fluoroquinolones and renin-angiotensin-system blockers was found. Renin-angiotensin-system blockers are a widely prescribed and popular class of cardiovascular medications used for a variety of diagnoses. This certainly requires taking a cautious approach against the concomitant use of these two drug classes when possible. Interestingly enough, the findings of absence of an increased risk of acute kidney injury with other antibiotics such as amoxicillin and azithromycin would support the hypothesis that this potential adverse association of fluoroquinolones with acute kidney injury is not a class effect of all antibiotics. That would allow physicians to use other classes of antibiotics in high-risk patients such as those on renin-angiotensin-system blockers or with pre-existing renal disease.
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