Pam Harrison

June 01, 2015

LONDON, United Kingdom — Remote ischemic preconditioning protects patients against acute kidney injury after cardiac surgery, according to results from a new study.

In addition, preconditioning significantly reduces the need for renal replacement therapy and the time spent in the intensive care unit (ICU).

"It's cheap and safe to do, and can easily be done following anesthesia," said Alexander Zarbock, MD, from University Hospital in Munster, Germany.

"We still have to confirm these data in a bigger trial and look for hard outcomes," he told Medscape Medical News. "Remote ischemic preconditioning is not ready for prime time yet, but it will be."

The study was presented here at the European Renal Association–European Dialysis and Transplant Association 52nd Congress, and was published online in JAMA to coincide with the presentation.

Dr Zarbock and his colleagues identified 240 patients from four centers who were at high risk for acute kidney injury, according to their Cleveland Clinic Foundation score. Half were randomized to undergo remote ischemic preconditioning; the other half, randomized to a sham procedure, served as the control group.

The preconditioning procedure involves placing a blood pressure cuff on the upper arm and inflating it for 5 minutes to a systolic pressure of at least 200 mm Hg. This is followed by a 5-minute reperfusion interval when the cuff deflates.

The procedure is done three times after the induction of anesthesia, which is administered in accordance with the standard of care.

In the 72 hours after surgery, the rate of development of acute kidney injury was significantly lower in the preconditioning group than in the control group (37.5% vs 52.5%; P = .02), for an absolute risk reduction of 15% (95% confidence interval [CI], 2.56 - 27.44).

The number of moderate and severe acute kidney injury episodes was also significantly lower in the preconditioning group than in the control group (12.5% vs 25.8%; P = .02). However, the number of mild acute kidney injury episodes was not significantly different between the two groups.

The need for renal replacement therapy was significantly lower in the preconditioning group than in the control group (5.8% vs 15.8%; P = .01), for an absolute risk reduction of 10% (95% CI, 2.25 - 17.75; P = .01).

And the length of stay in the ICU was significantly shorter in the preconditioning group than in the control group (3 vs 4 days; 95% CI, 0 - 2 days median difference; P = .04).

Biomarkers for Kidney Injury

Cardiac surgery led to a significant increase in the expression of biomarkers for acute kidney injury, including neutrophil gelatinase-associated lipocalin (P < .001) and two markers of cell cycle arrest — urinary insulin-like growth factor-binding protein 7 and tissue inhibitor of metalloproteinases-2 (P < .02). However, preconditioning significantly attenuated the release of biomarkers after surgery (P < .001).

"During remote ischemic preconditioning, different proinflammatory mediators are released. These mediators are filtered in the glomerulus, and then subsequently bind to the tubular epithelial cells and induce a cell cycle arrest," Dr Zarbock explained.

During cell cycle arrest, tubular epithelial cells are protected from further damage, he added.

"The early transient increase in biomarkers we saw in the study is protective against acute kidney injury, but biomarkers did not increase in all patients who received remote ischemic preconditioning," he reported.

It seems that "some patients are fine with three cycles of remote ischemic preconditioning, but others may need more. We have to find the right dose," said Dr Zarbock.

But the answer to the basic question — "Can our kidneys be fooled into protecting themselves?" — is yes, he said.

Study Findings "Extremely Important"

From a clinical perspective, these findings are "extremely important," said Denis Fouque, MD, from Université Claude Bernard Lyon in Villeurbanne, France, who is chair of the paper selection committee for the congress.

"We know that when the kidneys are impaired, it can lead to further hospitalization and even death, and patients may need dialysis sessions in the ICU, all of which adds to the gravity of the situation and prolongs recovery," he told Medscape Medical News.

"This solution is very cheap, and it's easy to find 15 minutes while you are preparing the patient for surgery to do this intervention," said Dr Fouque.

This study was funded by the German Research Foundation. Dr Zarbock reports receiving grant support and lecture fees unrelated to this study from Astute Medical.

JAMA. Published online May 29, 2015. Abstract

European Renal Association–European Dialysis and Transplant Association (ERA-EDTA) 52nd Congress: Abstract 15-LBA-3556. Presented May 29, 2015.

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