From the Guidelines
Azithromycin is not typically associated with a high risk of causing acute kidney injury (AKI) compared to other medications, including other macrolide antibiotics like clarithromycin or erythromycin, which can increase the risk of AKI when combined with certain statins due to pharmacokinetic interactions 1. When considering the potential for azithromycin to cause AKI, it's essential to evaluate the context of its use, including the presence of other nephrotoxins, the patient's baseline renal function, and the overall clinical scenario.
- The risk of AKI from azithromycin is lower compared to combinations of nephrotoxins such as NSAIDs, diuretics, and ACE inhibitors or ARBs, which can significantly increase the risk of AKI 1.
- Azithromycin does not powerfully inhibit cytochrome P450 enzyme CYP 3A4, which reduces the risk of pharmacokinetic drug interactions that could lead to AKI when co-administered with statins, unlike other macrolides like clarithromycin or erythromycin 1.
- The management of potential nephrotoxins, including azithromycin, involves assessing the temporal relationship between drug administration and AKI onset, considering alternative causes, and evaluating the response to drug withdrawal or reintroduction 1.
- Given the relatively safer profile of azithromycin regarding AKI risk, especially when compared to other antibiotic and medication combinations, its use should be considered in the context of the patient's overall clinical condition, weighing the benefits of treatment against the potential, though lower, risk of renal complications 1.
From the FDA Drug Label
Genitourinary: Interstitial nephritis and acute renal failure and vaginitis. The FDA drug label indicates that azithromycin can cause acute renal failure, which is another term for Acute Kidney Injury (AKI).
- Key points:
- Azithromycin may cause AKI, as stated in the post-marketing experience section of the label.
- The label also mentions interstitial nephritis as a possible side effect, which can lead to AKI.
- Caution is advised when administering azithromycin to patients with severe renal impairment 2.
From the Research
Azithromycin and Acute Kidney Injury (AKI)
- Azithromycin, an antibiotic, has been associated with acute kidney injury (AKI) in some cases, as reported in a study published in 2015 3.
- The study described a case of a 59-year-old male who developed azithromycin-induced acute interstitial nephritis (AIN), a form of AKI, after completing a 5-day course of azithromycin for an upper respiratory tract infection.
- The patient's serum creatinine concentration peaked at 11.4 mg/dl, and he required three sessions of hemodialysis, but his renal function improved with low-dose prednisone treatment.
Mechanisms of Antibiotic-Induced Nephrotoxicity
- Antibiotics, including azithromycin, can cause nephrotoxicity through various mechanisms, such as acute interstitial nephritis, acute tubular necrosis, and intratubular crystal deposition, as discussed in a 2020 study 4.
- A 2023 study 5 highlighted the importance of recognizing antibiotic-induced nephrotoxicity, which can lead to AKI, and the potential benefits of using novel biomarkers to detect kidney injury early.
Pharmacokinetics of Azithromycin in Renal Impairment
- A 1995 study 6 found that azithromycin's pharmacokinetics are not significantly affected by renal insufficiency, suggesting that the dosage regimen can be the same in patients with normal or impaired renal function.
Azithromycin and Major Adverse Kidney Events
- A 2022 study 7 investigated the association between early azithromycin receipt and major adverse kidney events (MAKE) in critically ill patients with sepsis-associated AKI, finding that azithromycin was independently associated with a decreased odds of MAKE at hospital discharge.