Angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use linked with decreased mortality after inpatient acute kidney injury.

1. In this retrospective cohort study looking at patients admitted to hospital with acute kidney injury, use of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker within six months was associated with decreased mortality.

2. Angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use was also associated with increased risk of hospitalization for a renal cause (hyperkalemia, acute kidney injury, or congestive heart failure).

Evidence Rating Level: 2 (Good)

Study Rundown: Acute kidney injury (AKI) is one of the most common complications in adult patients admitted to hospital and is associated with increased likelihood of hypertension, stroke, end-stage renal disease (ESRD) and death. This retrospective study using the Alberta kidney disease network population database found that angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (ACE/ARB) use within six months of discharge in patients with inpatient AKI was associated with decreased mortality, particularly amongst those patients with hypertension. Patients with ACE/ARB prescription after discharge had higher rates of hospital admission for a renal cause, specifically hyperkalemia, acute renal failure, and congestive heart failure. There was no difference in rates of progression to ESRD.

The large sample size, robust propensity matching, follow-up length as well as high accuracy of available pharmacy records all support this study’s conclusion. There were some notable limitations. Firstly, although all pre-specified, the large number of statistical analyses increase the likelihood of a false-positive result. Secondly, the necessity for patients to have a serum creatinine measurement within 180 days of hospital admission may have selected for patients with greater healthcare exposure, thereby limiting generalizability.

Click to read the study in JAMA Internal Medicine

Relevant Reading: Acute Kidney Injury Associates with Increased Long-Term Mortality

In-Depth [retrospective cohort]: This was a retrospective cohort study using the Alberta kidney disease network population based database. Inclusion criteria included adults age 18+ residing in Alberta and admitted to hospital between July 1, 2008 and March 31, 2013 with an acute kidney injury (AKI) occurring during hospitalization. AKI was defined as an increase of 50% or 0.3 mg/dL (26.5 mmol/L) from baseline. Exclusion criteria included death or progression to end-stage renal disease (ESRD) before or during the time the index hospitalization concluded. Patients were followed from discharge until March 31, 2015 (minimum 2 years). The intervention of interest was prescription of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (ACE/ARB) within 6 months of discharge from hospital. Prescription drug information was obtained from the Pharmaceutical Information Network database, which includes 96% of provincial prescribing data. The primary outcome was all cause mortality. Secondary outcomes included hospitalization for a renal cause, ESRD, and a composite outcome of ESRD or sustained doubling of sCr. A total of 59, 951 adults were admitted within the study period with inpatient AKI. 46,253 survived to discharge without developing ESRD before or during index hospitalization. Propensity matching was used to account for underlying differences. This propensity matching yielded 9456 matched pairs (across all covariates) for a final study cohort of 18, 912. These matched pairs were analyzed using multivariable cox proportional hazards regression models.

Overall mortality was lower in patients prescribed an ACE/ARB (aHR 0.85, 95% CI 0.81-0.89). Subgroup analyses demonstrated that this benefit was limited to patients with comorbid hypertension (aHR 0.84, CI 0.80 – 0.88). In addition, sensitivity analyses demonstrated an increased mortality risk for patients prescribed ACE/ARB within 90 days of discharge compared with 90 days – 6 months post discharge (HR 1.15, CI 1.03-1.28). Stopping use of ACE/ARB prescribed pre-admission was also associated with increased mortality risk (HR 1.23, 95% CI 1.17-1.30). There was no effect of ACE/ARB use on progression to ESRD or composite of ESRD and sustained doubling of sCr. Conversely, ACE/ARB use was also associated with higher risk of hospitalization for renal cause (aHR 1.28, 95% CI 1.12-1.46). These renal causes were mainly acute renal failure (aHR 1.25, 95% CI 1.08-1.46), hyperkalemia (aHR 1.56, 95% CI 1.07-2.27), and congestive heart failure (aHR 1.69, 95% CI 1.18-2.41).

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