Combining diuretics, anti-hypertensives and NSAIDs may pose risk of kidney injury

Combining diuretics with angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs) and nonsteroidal anti-inflammatory drugs (NSAIDs) increased risk of acute kidney injury, a study found.

Researchers conducted a nested, case-control study of data from primary care records in the U.K. that identified 487,372 people who received antihypertensive drugs from 1997 to 2008. Patients were tracked for a mean of 5.9 ± 3.4 years, generating more than 3 million person-years of follow-up. During this time, 2,215 were diagnosed with acute kidney injury that prompted hospital admission or dialysis (7 in 10,000 person-years).

Study results appeared online Jan. 8 at BMJ.

Taking a double-therapy combination of diuretics or ACE inhibitors or ARBs with NSAIDs was not associated with an increased rate of acute kidney injury. However, a triple-therapy combination of a diuretic with an ACE inhibitor or ARB and an NSAID was associated with a higher rate of kidney injury (rate ratio [RR], 1.31; 95% CI, 1.12 to 1.53). The risk was particularly elevated in the first 30 days of treatment (RR, 1.82; 95% CI, 1.35 to 2.46) and progressively decreased, becoming insignificant after more than 90 days of use (RR, 1.01; 95% CI, 0.84 to 1.23; P<0.001 for interaction).

The authors wrote, “Given that NSAIDs are widely used (40-60% as lifetime prevalence in the general population) and that a greater incidence rate of acute kidney injury was estimated among antihypertensive drugs users than in the general population, increased vigilance may be warranted when diuretics and angiotensin converting enzyme inhibitors or angiotensin receptor blockers are used concurrently with NSAIDs. In particular, major attention should be paid early in the course of treatment, and a more appropriate use and choice among the available anti-inflammatory or analgesic drugs could therefore be applied in clinical practice.”

An accompanying editorial noted that the study's confidence intervals were wide, that over-the-counter NSAID use could be unreported, that doctors who monitored for this effect may have stopped treatment before kidney injury occurred, and that drug-associated acute kidney injury is often a complication of other illnesses. Clinicians should talk to patients about risks and be vigilant for drug-associated acute kidney injury, the editorial stated, because, “The jury is still out on whether double drug combinations are indeed safe.”