What is the association between Acute Kidney Injury (AKI) and tetracyclines (antibiotics)?

From the Guidelines

Tetracyclines should be avoided in patients at risk of acute kidney injury (AKI) due to their potential nephrotoxicity, as suggested by the American Heart Association (AHA) recommendations 1. When considering the use of tetracyclines, it is essential to weigh the benefits against the potential risks, particularly in patients with pre-existing kidney disease or those taking other nephrotoxic medications.

• The primary mechanism of tetracycline-induced AKI involves direct tubular toxicity, particularly with expired or degraded tetracyclines which can form toxic metabolites.
• Risk factors for tetracycline-induced AKI include pre-existing kidney disease, dehydration, advanced age, and concurrent use of other nephrotoxic medications.
• Symptoms of tetracycline-induced AKI include decreased urine output, fluid retention, electrolyte abnormalities, and elevated serum creatinine. As recommended by the AHA, alternative antibiotics such as amoxicillin, cephalexin, and clindamycin can be used in patients at risk of AKI 1.
• For patients allergic to penicillin, clindamycin is the drug of choice, and 600 mg of clindamycin should be administered orally 1 h before the intervention 1.
• The dose adjustment is associated with the residual kidney function, and nephrotoxic drugs like tetracyclines and aminoglycoside antibiotics should be avoided entirely 1.

From the Research

Acute Kidney Injury Associated with Tetracyclines

• Tetracyclines are a class of antibiotics that have been associated with acute kidney injury (AKI) in some cases 2.
• The mechanisms of antibiotic-induced nephrotoxicity include glomerular injury, tubular injury or dysfunction, distal tubular obstruction from casts, and acute interstitial nephritis (AIN) mediated by a type IV (delayed-type) hypersensitivity response 3.
• Clinical manifestations of antibiotic-induced nephrotoxicity include acute tubular necrosis (ATN), AIN, and Fanconi syndrome 3.
• Tetracycline-induced acute interstitial nephritis is a rare cause of acute renal failure, with only a few reported cases in the literature 2.
• The risk factors for antibiotic-induced AKI include pre-existing chronic kidney disease, concomitant use of medication with nephrotoxic potential, medical comorbidities, coexisting drug therapies, and the dosage and therapeutic period of antibiotics 4, 5.

Pathophysiology and Biomarkers

• The pathophysiology of antibiotic-induced nephrotoxicity involves complex mechanisms, including immune-mediated responses and direct toxicity to renal cells 3, 6.
• Biomarkers such as cystatin C and urinary kidney injury molecule-1 (KIM-1) may be useful in early detection of AKI and optimizing dosing and duration of treatment with nephrotoxic antibiotics 3.
• MicroRNAs, such as miR-15a-5p, miR-192-5p, miR-155-5p, miR-486-5p, and miR-423-5p, have been identified as potential biomarkers for septic and toxic AKI in patients treated with nephrotoxic antibiotic agents 6.

Clinical Implications

• The use of tetracyclines and other nephrotoxic antibiotics requires careful consideration of the potential risks and benefits, particularly in patients with pre-existing kidney disease or other risk factors for AKI 4, 5.
• Early recognition and prevention of AKI are crucial to mitigating the morbidity and mortality associated with antibiotic-induced nephrotoxicity 4, 3.