Blood pressure agents, NSAID combo linked to kidney risks


Patients who take a combination of diuretics and either angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) and add NSAIDs, have an increased risk of acute kidney injury, according to a study online in BMJ.

Researchers from the Jewish General Hospital and McGill University in Montreal, Canada, wanted to assess whether certain combinations of antihypertensive drugs and NSAIDs are linked to an increased risk of kidney injury.

“These drugs are commonly used in combination, particularly by elderly patients,” said Samy Suissa, PhD, James McGill professor of epidemiology, biostatistics and medicine, McGill University, and director, Centre for Clinical Epidemiology, Lady Davis Research Institute - Jewish General Hospital.  “Moreover, acute kidney injury is a major public health concern, occurring in more than 20% of hospital inpatients.”

Researchers used UK Clinical Practice Research Datalink, a database of primary care records, and the Hospital Episodes Statistics database, a national registry of hospital admissions.

They identified 487,372 people who received ACE inhibitors, ARBs, and diuretics, with NSAIDs.

Patients were tracked for nearly 6 years, during which time 2,215 were diagnosed with acute kidney injury that prompted admission to hospital or dialysis (7 in 10,000 person years).

“Using these acute kidney injury cases and matched controls from the cohort, we estimated the relative risk of acute kidney injury associated with triple and double therapy,” Suissa told Formulary.

The results showed that patients taking a double therapy combination of either a diuretic or an ACE inhibitor or ARB with an NSAID were at no increased risk of kidney injury. However, a triple therapy combination of a diuretic with an ACE inhibitor or ARB and an NSAID was associated with a 31% higher rate of kidney injury.

“This risk is particularly elevated during the first month of triple combination treatment, with an 82% increase in the risk,” Suissa said.

“The 2 noteworthy findings of our study were that the elevated risk was concentrated in the first month of triple therapy and that no excess risk was detected with double therapy combination,” he said.

In an accompanying editorial, researchers at the London School of Hygiene and Tropical Medicine say this study “is an important step in the right direction” but “probably underestimates the true burden of drug-associated acute kidney injury.”

They suggest that clinicians advise patients of the risks and be vigilant for drug-associated acute kidney injury, and say “the jury is still out on whether double drug combinations are indeed safe.”

Suissa said that he and the researchers agree with the accompanying editorial. “Clinicians should advise patients of the risks and be vigilant for signs of drug-associated acute kidney injury during the first month of use,” he said.

Take away

The risk of acute kidney injury is particularly elevated during the first month of triple combination treatment.

For more on this study, go to


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