Diuretic Plus ACE Inhibitor Does Not Increase Acute Kidney Damage in Children

Deborah Brauser

January 14, 2010

January 14, 2010 (Miami Beach, Florida) — Using furosemide and angiotensin-converting-enzyme (ACE) inhibitors concurrently after cardiac surgery does not increase the risk for acute kidney injury (AKI) in young children, according to the results of a retrospective review presented here during a poster session at the Society of Critical Care Medicine 39th Critical Care Congress.

Dr. Jon Kaufman

"Neonates, infants, and children with heart disease are vulnerable to [AKI], which may occur as a result of poor systemic perfusion, the effects of cardiopulmonary bypass, or nephrotoxic medications," said Jon Kaufman, MD, cardiac intensive care physician at The Children's Hospital in Aurora, Colorado.

He noted that AKI can lead to an increased stay in the intensive care unit and has been linked to increased mortality.

"Other studies have looked at ACE inhibitors and the incidence of [AKI] in children with congenital heart disease. But to my knowledge, this is the first one that also looked at the co-use of diuretic therapy, which is given to almost every child that comes out of the [operating room] for bypass," said Dr. Kaufman.

He continued: "ACE inhibitors are used very freely in these patients, not only for postoperative hypertension, but also for the theoretical benefits of remodeling of the single ventricle. So we wanted to answer the question: Does our use of ACE inhibitors in conjunction with very high doses of diuretics lead to kidney injury?"

The investigators examined data on 319 patients younger than 2 years who received furosemide alone (n = 149; mean age, 5 months) or in combination with the ACE inhibitors captopril or enalapril/enalaprilat (n = 170; mean age, 3.7 months) while in The Children's Hospital critical intensive care unit after undergoing cardiac surgery between March 2007 and September 2008.

Data collected included cardiopulmonary bypass, cross-clamp, and circulatory arrest time; initial and peak serum creatinine; and use of additional common nephrotoxic medications, including ketorolac, gentamicin, cyclosporine, and other diuretics.

Modified Schwartz criteria were used to calculate serum creatinine clearance, and maximal degree of AKI was classified by pediatric Risk, Injury, Failure, Loss, and End-Stage Kidney Disease (pRIFLE) score.


Results showed that although the combination group had a higher incidence of the pRIFLE maximum score of "F" (renal failure) than the monotherapy group (31% vs 20%, respectively; odds ratio, 1.75; = .033), the use of an ACE inhibitor was not found to increase the chance of receiving the F score (= 0.85), after adjustment for patient age, the use of circulatory arrest during the operative course, the need for extracorporeal membrane oxygenation in the postoperative period, and the administration of gentamicin.

Overall, the chance of a pRIFLE score of F increased for circulatory arrest during surgical repair (= .002) and the use of gentamicin (= .012), chlorothiazide (= .044), or cyclosporine (= .012). Older age was associated with a decreased chance of a pRIFLE F score (< .0001).

Finally, those receiving both furosemide and ACE inhibitors had significantly longer cardiopulmonary bypass (= .04) and cross-clamp (= .03) times, but a lower postoperative creatinine clearance (54.4 vs 64.3 mL/min per 1.73 m2; = .01) than those receiving furosemide alone.

"When we accounted for all these other factors, we found no difference between the groups for kidney injury," said Dr. Kaufman. "Plus, none of the kids on both the ACE inhibitors and furosemide went on to require renal replacement therapy, and there was no increased mortality in that group."

"I think this study shows that using ACE inhibitors with diuretics is safe in this fragile and vulnerable patient population, and I think the findings will change our practice, in that we'll be less concerned about using them."

He added: "Given some of the limitations of the pRIFLE criteria, it would be interesting to next look at this in a different way, such as using biomarkers of renal injury."

Safe, but Monitoring Still Needed

"This was a reasonable comparison review, as a majority of patients in infancy following cardiac surgery do require furosemide at some point, although not as many require ACE inhibitors," said Critical Care Congress cochair Bruce Greenwald, MD, FCCM, FAAP, professor of clinical pediatrics and chief of the Division of Pediatric Critical Care Medicine at Cornell University Weill Medical College in New York City.

He added: "Considering the limitations of a retrospective study, I think [the investigators] did well in determining that there were no glaring differences in renal function between the 2 comparison groups, suggesting that the practice of using ACE inhibitors in combination with furosemide is safe."

However, Dr. Greenwald cautioned that close monitoring is still needed. "It's always important for clinicians to monitor renal function in patients who are receiving drugs that have the potential to be nephrotoxic. These findings should not cause clinicians to let their guard down, but it should reassure them that starting the 2 drugs together in this patient population is a reasonable thing to do based on these data."

Dr. Kaufman and Dr. Greenwald have disclosed no relevant financial relationships.

Society of Critical Care Medicine (SCCM) 39th Critical Care Congress: Abstract 417 Presented January 11, 2010.


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