Thida C. Tan

The assessment, serial evaluation, and subsequent sequelae of acute kidney injury (ASSESS-AKI) study: design and methods

BackgroundThe incidence of acute kidney injury (AKI) has been increasing over time and is associated with a high risk of short-term death. Previous studies on hospital-acquired AKI have important methodological limitations, especially their retrospective study designs and limited ability to control for potential confounding factors.MethodsThe Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) Study was established to examine how a hospitalized episode of AKI independently affects the risk of chronic kidney disease development and progression, cardiovascular events, death, and other important patient-centered outcomes. This prospective study will enroll a cohort of 1100 adult participants with a broad range of AKI and matched hospitalized participants without AKI at three Clinical Research Centers, as well as 100 children undergoing cardiac surgery at three Clinical Research Centers. Participants will be followed for up to four years, and will undergo serial evaluation during the index hospitalization, at three months post-hospitalization, and at annual clinic visits, with telephone interviews occurring during the intervening six-month intervals. Biospecimens will be collected at each visit, along with information on lifestyle behaviors, quality of life and functional status, cognitive function, receipt of therapies, interim renal and cardiovascular events, electrocardiography and urinalysis.ConclusionsASSESS-AKI will characterize the short-term and long-term natural history of AKI, evaluate the incremental utility of novel blood and urine biomarkers to refine the diagnosis and prognosis of AKI, and identify a subset of high-risk patients who could be targeted for future clinical trials to improve outcomes after AKI.

Visit-to-visit variability of blood pressure and death, end-stage renal disease, and cardiovascular events in patients with chronic kidney disease.

Objectives: Visit-to-visit variability of blood pressure (VVV of BP) is an important independent risk factor for premature death and cardiovascular events, but relatively little is known about this phenomenon in patients with chronic kidney disease (CKD) not yet on dialysis. Methods: We conducted a retrospective study in a community-based cohort of 114 900 adults with CKD stages 3–4 (estimated glomerular filtration rate 15–59 ml/min per 1.73 m2). We hypothesized that VVV of BP would be independently associated with higher risks of death, incident treated end-stage renal disease, and cardiovascular events. We defined systolic VVV of BP using three metrics: coefficient of variation, standard deviation of the mean SBP, and average real variability. Results: The highest versus the lowest quintile of the coefficient of variation was associated with higher adjusted rates of death (hazard ratio 1.22; 95% confidence interval 1.11–1.34) and hemorrhagic stroke (hazard ratio 1.91; confidence interval 1.36–2.68). VVV of BP was inconsistently associated with heart failure, and was not significantly associated with acute coronary syndrome and ischemic stroke. Results were similar when using the other two metrics of VVV of BP. VVV of BP had inconsistent associations with end-stage renal disease, perhaps because of the relatively low incidences of this outcome. Conclusion: Higher VVV of BP is independently associated with higher rates of death and hemorrhagic stroke in patients with moderate to advanced CKD not yet on dialysis.

Acute Kidney Injury and Risk of Heart Failure and Atherosclerotic Events

BACKGROUND AND OBJECTIVES AKI in the hospital is common and is associated with excess mortality. We examined whether AKI is also independently associated with a higher risk of different cardiovascular events in the first year after discharge. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We conducted a retrospective analysis of a cohort between 2006 and 2013 with follow-up through 2014, within Kaiser Permanente Northern California. We identified all adults admitted to 21 hospitals who had one or more in-hospital serum creatinine test result and survived to discharge. Occurrence of AKI was on the basis of Kidney Disease: Improving Global Outcomes diagnostic criteria. Potential confounders were identified from comprehensive inpatient and outpatient, laboratory, and pharmacy electronic medical records. During the 365 days after discharge, we ascertained occurrence of heart failure, acute coronary syndromes, peripheral artery disease, and ischemic stroke events from electronic medical records. RESULTS Among a matched cohort of 146,941 hospitalized adults, 31,245 experienced AKI. At 365 days postdischarge, AKI was independently associated with higher rates of the composite outcome of hospitalization for heart failure and atherosclerotic events (adjusted hazard ratio [aHR], 1.18; 95% confidence interval [95% CI], 1.13 to 1.25) even after adjustment for demographics, comorbidities, preadmission eGFR and proteinuria, heart failure and sepsis complicating the hospitalization, intensive care unit (ICU) admission, length of stay, and predicted in-hospital mortality. This was driven by an excess risk of subsequent heart failure (aHR, 1.44; 95% CI, 1.33 to 1.56), whereas there was no significant association with follow-up atherosclerotic events (aHR, 1.05; 95% CI, 0.98 to 1.12). CONCLUSIONS AKI is independently associated with a higher risk of cardiovascular events, especially heart failure, after hospital discharge.

Acute Kidney Injury Ascertainment Is Affected by the Use of First Inpatient Versus Outpatient Baseline Serum Creatinine

To the Editor: An important methodological issue concerning acute kidney injury (AKI) definitions is the choice of “baseline” serum creatinine (SCr). The most recent consensus definition proposes a rolling 48-hour window for AKI ascertainment during hospitalization, or the use of a baseline value that is “known or presumed to have occurred in the past 7 days.” However, significant misclassification in assigning AKI status can occur when admission or nadir inpatient SCr (as has been done in a number of studies) is used rather than a preadmission outpatient baseline. A wellrecognized concern with the use of admission SCr to define baseline kidney function is that it will be higher than a patient’s true baseline if communityacquired AKI is present, and therefore communityacquired AKI will be missed if the admission SCr is used to define baseline. However, animal and

Health Behaviors in Younger and Older Adults With CKD: Results From the CRIC Study

Introduction A cornerstone of kidney disease management is participation in guideline-recommended health behaviors. However, the relationship of these health behaviors with outcomes, and the identification of barriers to health behavior engagement, have not been described among younger and older adults with chronic kidney disease. Methods Data from a cohort study of 5499 individuals with chronic kidney disease was used to identify health behavior patterns with latent class analysis stratified by age <65 and ≥65 years. Cox models, stratified by diabetes, assessed the association of health behavior patterns with chronic kidney disease (CKD) progression, atherosclerotic events, and death. Logistic regression was used to assess for barriers to health behavior engagement. Results Three health behavior patterns were identified: 1 “healthy” pattern, and 2 “less healthy” patterns comprising 1 pattern with more obesity and sedentary activity and 1 with more smoking and less obesity. Less healthy patterns were associated with an increased hazard of poor outcomes. Among participants <65 years of age, the less healthy patterns (vs. healthy pattern) was associated with an increased hazard of death in diabetic individuals (hazard ratio [HR] = 2.17, 95% confidence interval [CI] = 1.09–4.29; and HR = 2.50, 95% CI = 1.39–4.50) and cardiovascular events among nondiabetic individuals (HR = 1.49, 95% CI = 1.04–2.43; and HR = 2.97, 95% CI = 1.49–5.90). Individuals with the more obese/sedentary pattern had an increased risk of CKD progression in those who were diabetic (HR = 1.34, 95% CI = 1.13–1.59). Among older adults, the less healthy patterns were associated with increased risk of death (HR = 2.97, 95% CI = 1.43–6.19; and HR = 3.47, 95% CI = 1.48–8.11) in those who were nondiabetic. Potential barriers to recommended health behaviors include lower health literacy and self-efficacy. Conclusion Identifying health behavior patterns and barriers may help target high-risk groups for strategies to increase participation in health behaviors.

Non-recovery from dialysis-requiring acute kidney injury and short-term mortality and cardiovascular risk: a cohort study.

BackgroundThe high mortality and cardiovascular disease (CVD) burden in patients with end-stage renal disease (ESRD) is well-documented. Recent literature suggests that acute kidney injury is also associated with CVD. It is unknown whether patients with incident ESRD due to dialysis-requiring acute kidney injury (AKI-D) are at higher short-term risk for death and CVD events, compared with incident ESRD patients without preceding AKI-D. Few studies have examined the impact of recovery from AKI-D on subsequent CVD risk.MethodsIn this retrospective cohort study, we evaluated adult members of Kaiser Permanente Northern California who initiated dialysis from January 2009 to September 2015. Preceding AKI-D and subsequent outcomes of death and CVD events (acute coronary syndrome, heart failure, ischemic stroke or transient ischemic attack) were identified from electronic health records. We performed multivariable Cox regression models adjusting for demographics, comorbidities, medication use, and laboratory results.ResultsCompared to incident ESRD patients who experienced AKI-D (n = 1865), patients with ESRD not due to AKI-D (n = 3772) had significantly lower adjusted rates of death (adjusted hazard ratio [aHR] 0.56, 95% CI: 0.47–0.67) and heart failure hospitalization (aHR 0.45, 0.30–0.70). Compared to AKI-D patients who did not recover and progressed to ESRD, AKI-D patients who recovered (n = 1347) had a 30% lower adjusted relative rate of death (aHR 0.70, 0.55–0.88).ConclusionsPatients who transition to ESRD via AKI-D are a high-risk subgroup that may benefit from aggressive monitoring and medical management, particularly for heart failure. Recovery from AKI-D is independently associated with lower short-term mortality.

Research LetterAcute Kidney Injury Ascertainment Is Affected by the Use of First Inpatient Versus Outpatient Baseline Serum Creatinine

To the Editor: An important methodological issue concerning acute kidney injury (AKI) definitions is the choice of “baseline” serum creatinine (SCr). The most recent consensus definition proposes a rolling 48-hour window for AKI ascertainment during hospitalization, or the use of a baseline value that is “known or presumed to have occurred in the past 7 days.” However, significant misclassification in assigning AKI status can occur when admission or nadir inpatient SCr (as has been done in a number of studies) is used rather than a preadmission outpatient baseline. A wellrecognized concern with the use of admission SCr to define baseline kidney function is that it will be higher than a patient’s true baseline if communityacquired AKI is present, and therefore communityacquired AKI will be missed if the admission SCr is used to define baseline. However, animal and

AKI Ascertainment is Affected by the Use of First Inpatient versus Outpatient Baseline Serum Creatinine

To the Editor: An important methodological issue concerning acute kidney injury (AKI) definitions is the choice of “baseline” serum creatinine (SCr). The most recent consensus definition proposes a rolling 48-hour window for AKI ascertainment during hospitalization, or the use of a baseline value that is “known or presumed to have occurred in the past 7 days.” However, significant misclassification in assigning AKI status can occur when admission or nadir inpatient SCr (as has been done in a number of studies) is used rather than a preadmission outpatient baseline. A wellrecognized concern with the use of admission SCr to define baseline kidney function is that it will be higher than a patient’s true baseline if communityacquired AKI is present, and therefore communityacquired AKI will be missed if the admission SCr is used to define baseline. However, animal and

Short-Term Outcomes and Factors Associated With Adverse Events Among Adults Discharged From the Emergency Department After Treatment for Acute Heart Failure

Background Although 80% of patients with heart failure seen in the emergency department (ED) are admitted, less is known about short-term outcomes and demand for services among discharged patients. Methods and Results We examined adult members of a large integrated delivery system who visited an ED for acute heart failure and were discharged from January 1, 2013, through September 30, 2014. The primary outcome was a composite of repeat ED visit, hospital admission, or death within 7 days of discharge. We identified multivariable baseline patient-, provider-, and facility-level factors associated with adverse outcomes within 7 days of ED discharge using logistic regression. Among 7614 patients, mean age was 77.2 years, 51.9% were women, and 28.4% were people of color. Within 7 days of discharge, 75% had outpatient follow-up (clinic, telephone, or e-mail), 7.1% had an ED revisit, 4.7% were hospitalized, and 1.2% died. Patients who met the primary outcome were more likely to be older, smokers, have a history of hemorrhagic stroke, hypothyroidism, and dementia, and less likely to be treated in a facility with an observation unit. In multivariable analysis, higher comorbidity scores and history of smoking were associated with a higher odds of the primary outcome, whereas treatment in a facility with an observation unit and presence of outpatient follow-up within 7 days were associated with a lower odds. Conclusions We identified selected hospital and patient characteristics associated with short-term adverse outcomes. Further understanding of these factors may optimize safe outpatient management in ED-treated patients with heart failure.