A 45 y/o patient with diabetes mellitus type II and mild congestive heart failure needs a non-steroidal anti-inflammatory agents (NSAID) for some arthritis. Acetaminophen and aspirin have not relived his pain nor helped his range of motion or early morning joint stiffness. His labs are normal except a slightly elevated glucose and a serum creatinine of 1.3 mg/dL.

The medical student wants to start indomethacin 25mg po TID as his NSAID.

Do you concur with the student? Why or why not?

No. Although indomethacin is a very potent anti-inflammatory agent, it is one of the most toxic to the kidneys. Aspirin and the non-acetylated salicylates are some of the least nephrotoxic. Acetaminophen is also fairly innocuous and is the drug of choice for osteoarthritis. ALL other NSAIDs are nephrotoxic, including the COX2 agents.

If aspirin, other non-acetylated salicylates, or acetaminophen has failed, one NSAID that MAY be less nephrotoxic to the kidneys is sulindac. Sulindac produces a less marked inhibition of renal prostaglandin synthesis. The mechanism isn't clear but may be related to its rapid metabolism of active drug. Sulindac is a pro-drug which is metabolized to the active component.

In the kidney, vasodilatory prostaglandins work opposite the vasoconstrictive effects of angiotensin II in the efferent arteriole to maintain renal blood flow and perfusion pressure across the glomerulus. Lack
of or inhibition of these prostaglandins allows angiotensin II to predominate and cause significant vasoconstriction, limiting renal blood flow.

Although sulindac may be less likely to impair renal function, careful monitoring is essential since ALL NSAIDs are nephrotoxic and the 'protection' offered by sulindac is NOT absolute.