So far,
the major complications associated with NSAID use appear to deal with the
gastrointestinal lining and liver. However, since all the systems work
together, this class of drug surely has an effect on other organ systems, as
well. We have seen recently that most NSAIDs work through inhibition of the
production of prostaglandins. While this family of mediators is often
associated with pain and fever, prostaglandins have other regulatory roles in
the body that are undoubtedly affected if they are down-regulated. One such
role is in the kidneys, where the prostaglandin family is involved in both the
regulation of sodium reabsorption and activation of the rennin-angiotensin
system during periods of decreased renal perfusion.
In healthy individuals, the renal effects of NSAID therapy are
mild because kidney function is not dependent on the presence of
prostaglandins. However, in patients with compromised renal perfusion, the
down-regulation of the prostaglandins can result in various systemic issues.
The most common kidney related side effect of NSAID use is peripheral edema.
Without prostaglandins to inhibit sodium reabsorption, water is retained in
excess. This may lead to edema, weight gain, and could aggravate preexisting
cardiovascular problems due to an increase in plasma volume.
I believe the review posted below does a good job linking together various systems that are affected by NSAID use. If anyone finds articles or studies implicating NSAID use with defects in other systems, please post them here.
Here is the review talking about the effects of NSAIDs on kidney
function and the mechanism behind it:
http://www.medscape.org/viewarticle/422939_3
The effects that NSAIDs have on kidney function is definitely something to consider. Water retention in particular, as Corey mentioned, is a big problem for an array of disease states, including congestive heart failure and liver failure. We talked about how COX-1 inhibition of traditional NSAIDs is what causes the gastrointestinal issues. Looking into this a bit, the inhibition of COX-2 in the kidney is what seems to cause water retention problems. I would think that because of this, using a selective COX-2 NSAID like Celebrex (celecoxib) would carry an increased renal risk.
ReplyDeleteAfter a little bit of searching, there are some conflicting studies comparing traditional NSAIDs like ibuprofen to celecoxib, weighing them against each other. Some say celecoxib has a decreased risk, some say that ibuprofen and celecoxib should be treated similarly when considering renal risk. Here is a more recent study which found that celecoxib is not as hard on the cardiovascular/renal function as ibuprofen: http://www.hindawi.com/journals/jt/2011/862153/
I would still say that NSAIDs shouldn't be used by those with renal or cardiovascular issues, but it seems like COX-2 selective inhibitors may desirable alternative to traditional NSAIDs, if only slightly.