ACE Inhibitors May Improve Survival after Acute Kidney Injury

HONG KONG—ACE inhibitors (ACEIs) may decrease mortality and need for dialysis in hospitalized patients with acute kidney injury (AKI), according to findings presented at the 2013 World Congress of Nephrology.

In a secondary analysis of data from patients in the RENAL (Randomized Evaluation of Normal vs. Augmented Level) renal replacement therapy (RRT) study, Australian researchers found a 65% higher survival rate at 90 days post-discharge and significantly fewer days on dialysis with use of ACEIs.

Lead analyst Amanda Wang, PhD, of the George Institute for Global Health in Camperdown, New South Wales, cautioned, however, that “the possibility of unmeasured residual confounders remains, and they could impact the results.”

The RENAL study involved 1,508 patients with AKI who were randomized to either low-intensity (25 mL/kg/h) or high-intensity (40 mL/kg/h) continuous RRT. It was conducted at 35 ICUs in Australia and New Zealand from 2006-2008.

Dr. Wang and senior author Martin Gallagher, MBBS, MPH, PhD, of the Sydney Medical School, and others performed a post-hoc analysis of the data, focusing on the effect of ACEIs. They analyzed information from the 128 individuals on ACEIs and the 1,321 who were not on ACEIs, all of whom had complete information ranging from days on mechanical ventilation to baseline estimated glomerular filtration rate.

Overall, patients taking ACEIs had better health parameters and outcomes, with a few exceptions. Significantly fewer had severe sepsis at baseline (34.5% vs. 50.9%), they had lower APACHE III scores (97.9 vs. 102.9), more ICU-free days (60.7 vs. 47.5), hospital-free days (40.4 vs. 31.4) and RRT-free days (20.7 vs. 17.0). On average, however, patients taking ACEIs had more days on mechanical ventilation on average (11.1 vs. 6.9) and higher Sequential Organ Failure Assessment-Cardiovascular (SOFA CV) scores (3.2 vs. 2.8).

“The division into participants receiving ACEIs and those not receiving ACEIs for this study was done post-randomization so there are notable differences between the groups,” Dr. Wang said. “The likely reason for this was the very high mortality in the early phase of the RENAL study, with the patients who survived the early period being very sick – and also having more opportunity for exposure to ACEIs.”

Additional analyses showed that ACEI use was associated with a 65% decreased risk of 90-day mortality and a 69% decreased risk of 28-day mortality.

In addition, they selected a group of patients who had survived for five or more days in the ICU and found that ACEI use was still associated with a survival benefit and less dialysis requirement, although not less hospital or ICU bed-day use.

The positive effects of ACEIs are likely due to their anti-inflammatory effects, positive impacts on cardiac function and anti-fibrotic properties that may help prevent scarring in patients with kidney injury, Dr. Wang noted.

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