Study design / outcomes
This is a 9,000 individual, randomized, placebo-controlled, parallel-group clinical trial of enalaprilat versus placebo for the treatment of hospital-acquired acute kidney injury.
Fear of further reducing glomerular filtration rate in the damaged kidney has led nephrologists to avoid the use of ACE-inhibitors in patients with AKI. While ACE-inhibitors do indeed decrease glomerular filtration rate, they increase renal blood flow by dilating the efferent arteriole, which supplies the vasa recta. The cells in the renal medulla are particularly susceptible to ischemic insult due to the hypoxic environment created by low blood flow through the vasa recta, even under normal circumstances. In AKI, these cells begin to undergo hypoxic and ischemic damage. By treating with ACE-inhibition in early AKI, we will increase medullary blood flow, restoring some of these cells to aerobic respiratory status and thus improve patient outcomes.
Given that ACE-inhibition is expected to increase serum creatinine and possibly dialysis rates, this study is powered to detect a difference in all-cause inpatient mortality of 2 absolute percentage points. Assuming a baseline risk of mortality of 10%, we will be powered to detect a relative risk reduction of 20%.