Table 1.

Altered bioactions of furosemide in critically ill patients with acute kidney injury.

Target abnormality	Mechanism	References
Hypoalbuminemia	Impaired furosemide delivery to nephron	23,24
Loss of epithelial cell polarity	Redistribution of Na/K + ATPase, impairing secondary active transport of organic acid.	25
Oliguria	Toxic plasma levels of furosemide	26
Uremic organic acids accumulation	Competiton with furosemide at the OAT1/OAT3 transporter site	27,28
Severe metabolic acidosis	Competiton with furosemide at the OAT1/OAT3 transporter site	27,28
Elevated OAT1/OAT3 (+/−OAT4) transporter secretion in urine	Tubular damage and destruction	29
Vasopressin administration	Increase expression of NKCC2 transporter and promote insertion into TAL of loop of Henle	18,30
Cephalosporin administration	Competition with furosemide at the OAT1/OAT3 transporter site	27,28