A study published in the British Medical Journal (2013;346:8525) revealed that combination therapy with three drug classes led to a 31% increase in risk of acute kidney injury, one of the top adverse drug events leading to hospitalization. The study was a population-based including 487,372 adults, average age 77, followed for an average of 5.9 years who started therapy between Jan. 1997 and Dec. 2008. The researchers reviewed combination dual-therapy, defined as the combination of either a diuretic, ace inhibitor (ACEI) or angiotensin receptor blocker (ARB), in addition to an NSAID (ibuprofen, naproxen, etc.), versus triple-therapy, defined as the combination use of a diuretic, and an ACE or ARB, in addition to an NSAID.
Use of dual-therapy was NOT associated with any increase in risk of kidney injury, but triple-therapy was associated with a 31% higher risk of acute kidney injury, mostly within the first 30 days of combination use. Since acute kidney damage is a leading adverse drug event leading to harm and hospitalization in older adults, it is most wise to identify scenarios where there is a proven increase in risk for harm and either avoid those therapies or increase the monitoring of those therapies to mitigate an adverse drug event before serious harm occurs. Lack of monitoring has been cited as the cause of about 40 to 60% of all adverse drug events so improvements in this area can make an impact. However, the use of NSAIDs in older adults by themselves are considered potentially inappropriate medications and should be used short-term and at the lowest doses, if at all. My take on this would be if NSAIDs were avoided all together, then the increased reporting of acute kidney injury would not have been found.