Does Sulindac Affect Renal Function Less Than Other NSAIDs?
Question: Does Sulindac Affect Renal Function Less Than Other NSAIDs?
Answer: Nonsteroidal anti-inflammatory drugs (NSAIDs) act by inhibiting cyclooxygenase (COX) to prevent the formation of prostaglandins produced in response to painful stimuli; this decreases the number of pain impulses received by the central nervous system (CNS).1 Prostaglandins normally are present within the kidneys and decrease vascular resistance and enhance organ perfusion there. In most patients, renal prostaglandin release is low; however, in patients with glomerular disease, renal insufficiency, or hypercalcemia, renal prostaglandins play an important role. If the process of renal prostaglandin production is inhibited, as can occur with NSAID use, renal perfusion may be decreased and blood flow redistributed to the cortex, which may lead to acute renal dysfunction.2 Sulindac (Clinoril), a nonselective NSAID, has been hypothesized to have decreased adverse renal effects because of its decreased COX inhibition and rapid renal metabolism compared to other NSAIDs.3
Much of the literature evaluating renal effects of sulindac has focused on measuring the renal excretion of prostaglandins. Other NSAIDs have been found to decrease renal prostaglandin excretion by 50%, with lesser to no excretion reported with sulindac.4 It is not clear whether the decrease in prostaglandin excretion correlates with clinical decreases in renal effects.
Evidence regarding clinically significant renal effects of sulindac is conflicting. More than 20 studies and case reports have been reported in the literature evaluating renal effects with sulindac.4-7 These studies, which have been small with only 3 to 12 subjects, have evaluated sulindac 200 mg twice daily for 1 to 28 days in healthy patients as well as patients with kidney or hepatic dysfunction. Reports primarily have found no significant differences in glomerular filtration rate (GFR) following treatment with sulindac.4,5 Serum creatinine reportedly was increased from 1.88 mg/dL at baseline to 2.16 mg/dL at day 11 (P<0.02) in a study of 12 women with decreased renal function who were assigned to take sulindac daily for 11 days.6 Case reports of renal effects associated with sulindac—due to overdoses as well as with therapeutic doses in elderly patients—have been reported. Increases in blood urea nitrogen and serum creatinine returned to baseline following discontinuation of sulindac.4,7
In summary, initially, it was thought that sulindac had lesser effects on prostaglandins within the kidneys compared with other NSAIDs, and it, therefore, was hypothesized to be renal sparing. Evidence supporting or refuting renal-sparing abilities of sulindac is lacking; only small, short-term studies have been conducted. Most of these studies have found no significant changes in GFR or serum creatinine. Patients who are at risk of renal dysfunction with other NSAIDs, including patients who are elderly, have current renal dysfunction, congestive heart failure, or cirrhosis, or are volume depleted, also may be at greater risk of developing renal dysfunction with sulindac. More frequent monitoring may be required in these patients, as is required with any other NSAID.
Deborah Helmink, PharmD Candidate
Southern Illinois University Edwardsville
School of Pharmacy
Erin M. Timpe Behnen, PharmD, BCPS
Drug Information and Wellness Center
Department of Pharmacy Practice
Southern Illinois University Edwardsville School of Pharmacy