Feldman HI, Kinman JL, Berlin JA, Hennessy S, Kimmel SE, Farrar J, et al
Ketorolac: the risk of acute renal failure
Am Soc Nephrol
J Am Soc Nephrol (abstract) (Sep) 7:1372 1996

Ketorolac (Toradol) is an injectable nonsteroidal anti-inflammatory drug (NSAID) used for pain management. Cases of acute renal failure have been reported associated with its use. NSAID's cause two different forms of acute renal failure: hemodynamically-mediated and acute interstitial nephritis .

These investigators performed a cohort study of the incidence of acute renal failure during more than 10,000 courses of parenteral ketorolac compared to a similar number of parenteral opioid courses. The overall risk of acute renal failure, defined as a 50 % increase in serum creatinine and an explicit physician diagnosis, was only 0.3 %. The multivariate adjusted rate ratio for acute renal failure comparing ketorolac to opioids was 1.02 for treatment of 5 days or shorter duration and 3.5 for patients treated for more than 5 days. However, the 95% confidence interval overlaps a rate ratio of 1.0 for both groups. The investigators conclude that short term use of ketorolac does not increase the likelihood of acute renal failure, but that treatment with ketorolac for longer than 5 days may increase the risk of acute renal failure.

Comment: Renal prostaglandins do not normally play a major role in the regulation of renal hemodynamics. However, the basal rate of vasodilator prostaglandin synthesis is enhanced in states of effective volume depletion, such as heart failure, hepatic cirrhosis, and true volume depletion due to gastrointestinal or renal losses. In any of the these settings, vasodilator prostaglandins act to preserve renal blood flow and glomerular filtration rate. This is particularly important with decreased effective volume in which the prostaglandins antagonize the vasoconstrictor effects of angiotensin II and norepinephrine.

Because of the very large size of the study population and the relatively few numbers of patients at increased risk of NSAID induced renal failure, this study may be too insensitive to determine the relative risk of ketorolac induced acute renal failure. (George R. Aronoff, M.D., University of Louisville, Kentucky)

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Am Soc Nephrol
ARF etiology : Other drug-associated ARF