NSAIDs plus ace-i or arb with diuretics assoc with acute kidney injury

Not a lot of data around about combo hypertensive drug interactions assoc with acute kidney dz. We know that NSAIDs are assoc with kidney dz through their inhib of prostacyclin synthesis (and assoc renal afferent arteriolar vasoconstriction). ACE-I/ARBs assoc with dec glomerular filtration (from efferent arteriolar vasodilation). Diuretics assoc with hypovolemia. So, this study done which looked at huge database of pts with htn in the UK -- clinical practice research datalink, with almost 500K people on antihypertensives and follow up of 6 years (See htn nsaid plus ace diur inc kidney injury bmj 2013 indropbox). They linked pts in their electronic database with those who were admitted to the hospital for acute kidney injury as their admitting diagnosis. They assessed use of NSAIDS and which antihypertensives the pts were on, in a nested case-controlled study.  Results:
 
-- 2215 cases of acute kidney injury (7/10,000 person-yrs)
--double combination therapy (NSAID plus diuretic, ACE-I or arb) not assoc with acute kidney injury
--triple  combo therapy (NSAID plus combo of diruetic plus either ACE-i or arb) was assoc with 31% increased risk of acute kidney injury
-- (not surprisingly), on comparing cases and controls, cases (who required more meds) were sicker overall, with more hosp admissions, more likely to have diabetes and other cardiovasc dz.
--analysis of secondary endpoints found
        --highest risk was in the first 30 days of the triple therapy (82% increase). Much of the 31% increase noted above was driven by this increase in the first 30 days
        --more pronounced effect with longer acting NSAIDs (those with half-life > 12 hours -- the ones of more concern in our patients are: naproxen, piroxicam, nabumetone and sulindac)
 
So, not a randomized controlled trial, but pretty impressive data (a bit surprising that no increase in acute kidney injury with NSAIDs alone, or in combo with any antihypertensive, but they are really using hard endpoint of severe enough renal failure to lead to hospital admission). A difficult clinical conundrum, since we have lots of hypertensive patients requiring multiple meds and lots of patients who need NSAIDs in spite of our attempts to minimize usage.  One potential solution is to minimize diuretics.  As i sent out previously on htn treatment, the NICE recommendations (that is the national institute for clinical excellence, in the UK) strongly pushes for use of calcium channel blockers as first line (or ACE-i in younger patients not of african-caribbean background). So, we could stick more with CCBs as first line (by the way, no clear clinical indication that i know of to use ACE-i or arb's in diabetic patients who do not have proteinuria)

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