Does azithromycin (a macrolide antibiotic) affect kidney function, particularly in patients with pre-existing impaired renal function (kidney disease)?

Azithromycin and Kidney Function

Azithromycin does not require dose adjustment in patients with renal impairment and is not significantly nephrotoxic, making it safe for use in patients with kidney disease. 1

Renal Dosing and Pharmacokinetics

No dose adjustment is necessary for azithromycin in renal insufficiency, even in severe cases. The FDA label explicitly states that no dosage adjustment is recommended for subjects with renal impairment (GFR ≤80 mL/min), though caution should be exercised in severe renal impairment (GFR <10 mL/min) where AUC increases by 35% 1. This contrasts sharply with other antibiotics:

• Azithromycin is primarily eliminated via the liver (biliary excretion), not the kidneys - only approximately 6% of the administered dose appears as unchanged drug in urine 1
• The mean AUC and Cmax increased only 4.2% and 5.1% respectively in mild to moderate renal impairment (GFR 10-80 mL/min) compared to normal renal function 1, 2
• Even in severe renal impairment (GFR <10 mL/min), the increases (35% AUC, 61% Cmax) are modest compared to renally-cleared antibiotics 1
• The distribution volume (16 L/kg body weight) and nonrenal clearance remain unaffected by renal insufficiency 2

Comparison with Other Macrolides

Azithromycin is distinctly safer than other macrolides regarding drug-induced kidney injury. The ADQI guidelines specifically note that azithromycin does not powerfully inhibit cytochrome P450 enzyme CYP3A4, unlike clarithromycin or erythromycin, resulting in fewer hospitalizations for AKI from rhabdomyolysis when combined with statins 3. This pharmacokinetic difference makes azithromycin the preferred macrolide in patients with renal concerns.

Rare Nephrotoxicity Risk

While azithromycin is generally safe for the kidneys, acute interstitial nephritis (AIN) is a rare but documented adverse effect that clinicians must recognize:

• Drug-induced AIN can occur with azithromycin, though it is uncommon 4, 5
• Case reports document biopsy-proven azithromycin-induced AIN requiring hemodialysis, with onset typically 1-2 weeks after completing therapy 5, 6
• Recurrent AIN can occur with re-exposure and may be more severe, potentially causing permanent renal injury despite corticosteroid treatment 6
• Clinical presentation includes rapid deterioration of renal function, nausea, vomiting, and oliguria/anuria 5

Clinical Management Algorithm

For patients with pre-existing renal disease:

• Use standard azithromycin dosing (500 mg day 1, then 250 mg days 2-5) regardless of GFR, except in severe impairment (GFR <10 mL/min) where closer monitoring is warranted 1, 2
• Monitor for signs of AIN if the patient develops acute kidney injury during or within 2 weeks after azithromycin therapy - consider alternative diagnoses but maintain high suspicion for drug-induced AIN 5
• Avoid re-exposure in patients with prior azithromycin-associated renal injury, as recurrence risk is high and potentially more severe 6
• No routine renal function monitoring is required for azithromycin use in stable renal disease, unlike aminoglycosides or other nephrotoxic antibiotics 1, 2

Key Distinction from Nephrotoxic Antibiotics

Azithromycin stands in stark contrast to truly nephrotoxic antibiotics that require dose adjustment and intensive monitoring:

• Aminoglycosides (streptomycin, amikacin, kanamycin) cause nephrotoxicity in 2-8.7% of patients and require dosing frequency reduction to 2-3 times weekly in renal impairment 3
• Capreomycin causes significant renal toxicity requiring discontinuation in 20-25% of patients 3
• These agents are cleared almost exclusively by the kidney and accumulate dangerously in renal impairment, unlike azithromycin 3