Factors influencing ketorolac-associated perioperative renal dysfunction

Area of Science:

• Pharmacology
• Nephrology
• Toxicology

Background:

• Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used for postoperative pain management.
• Concerns exist regarding NSAIDs' potential adverse effects on renal function.
• Ketorolac is an NSAID frequently prescribed for moderate to severe pain.

Purpose of the Study:

• To investigate the renal effects of ketorolac, particularly in combination with gentamicin, in a rat model.
• To assess the impact of different ketorolac dosages and co-administration with gentamicin on kidney function and structure.

Main Methods:

• Fischer 344 rats underwent laparotomy and anesthesia.
• Animals were assigned to various treatment groups: control, ketorolac (low/high dose), dehydration-ketorolac, gentamicin, and gentamicin-ketorolac combination.
• Renal function was evaluated using para-aminohippurate and iothalamate clearances, serum/urine electrolytes, osmolality, urea, and creatinine.
• Kidney histology was examined for signs of damage.

Main Results:

• The combination of ketorolac and gentamicin (GK group) resulted in severe, consistent changes in renal function.
• Histological examination of the GK group revealed widespread acute tubular necrosis.
• Mild renal dysfunction was observed in the gentamicin-only group (G group).
• No significant renal function changes were noted in control, ketorolac-only, or dehydration-ketorolac groups.

Conclusions:

• The combination of ketorolac and gentamicin is deleterious to renal function in this postoperative rat model.
• This drug combination can lead to severe acute tubular necrosis and significant impairment of kidney function.
• Caution is advised when co-administering ketorolac with gentamicin due to potential nephrotoxicity.