Effect of Intensive vs Standard Blood Pressure Control on Acute Kidney Injury and Subsequent Cardiovascular Outcomes and Mortality: Findings from the SPRINT EHR Study

Background: Adjudication of inpatient acute kidney injury (AKI) in the Systolic Blood Pressure Intervention Trial (SPRINT) was based on billing codes and admission and discharge notes. The purpose of this study was to evaluate the effect of intensive vs. standard blood pressure (BP) control on creatinine-based inpatient and outpatient AKI, and whether AKI was associated with cardiovascular disease (CVD) and mortality. Methods: We linked electronic health record (EHR) data from 47 clinic sites with trial data to enable creatinine-based adjudication of AKI. Cox regression was used to evaluate the effect of intensive BP control on the incidence of AKI and the relationship between incident AKI and CVD and all-cause mortality. Results: 3644 participants had linked EHR data. A greater number of inpatient AKI events were identified using EHR labs (187 intensive vs 155 standard) as compared to serious adverse event (SAE) adjudication in the trial (95 intensive vs 61 standard). Intensive treatment increased risk for SPRINT-adjudicated inpatient AKI (HR 1.51, 95% CI 1.09 - 2.08) and for creatinine-based outpatient AKI (HR 1.40, 95% CI 1.15 - 1.70), but not for creatinine-based inpatient AKI (HR 1.20, 0.97 - 1.48). Irrespective of the definition (SAE or creatinine-based), AKI was associated with increased risk for all-cause mortality, but only creatinine-based inpatient AKI was associated with increased risk for CVD. Conclusions: Creatinine-based ascertainment of AKI, enabled by EHR data, may be more sensitive and less biased than traditional SAE adjudication. Identifying ways to prevent AKI may reduce mortality further in the setting of intensive BP control.