AKI and Increased Risk of Heart Failure in Hospitalized US Veterans

The incidence of acute kidney injury (AKI) in the US population is increasing. AKI is associated with poor long-term outcomes such as the development of chronic kidney disease (CKD) and death. There may also be an association between AKI and subsequent atherosclerotic cardiovascular disease.

Patients with CKD commonly develop heart failure as a manifestation of cardiovascular disease; in patients with CKD, the risk for heart failure is 3-fold greater than in patients without CKD. The mechanisms that link kidney disease and heart failure may also exist or become accelerated in the setting of AKI.

According to Misha Bansal, MD, and colleagues, it is unclear whether there is an association between AKI and subsequent incident heart failure. The researchers recently conducted a national cohort observational study designed to examine this association of AKI with incident heart failure in a cohort of US veterans. Results of the study were reported online in the American Journal of Kidney Diseases [doi:10.1053/j.ajkd.2017.08.027].

The researchers collected a national retrospective cohort of 6,390,410 adult patient hospitalizations in 116 Veterans Affairs hospitals from January 1, 2002, through December 31, 2013. To allow for 2 years of data collection prior to the index hospitalization to define baseline covariates and allow 2 years of follow-up time following the index hospitalization, the current analysis included 4,970,665 patients ≥18 years of age with qualifying hospitalizations after January 1, 2004, through December 31, 2011.

The primary exposure was the first AKI event during the index hospitalization. AKI was determined using creatinine laboratory value data and dialysis procedure codes collected during the index hospitalization. The primary predictor of AKI at any stage was defined based on the Kidney Disease: Improving Global Outcomes creatinine-based staging criteria. Incident heart failure was defined as either (1) hospitalization occurring after the index hospitalization with the appropriate validated primary or secondary International Classification of Diseases-Ninth Revision (ICD-9) codes or (2) two or more outpatient visits occurring after the index hospitalization with the heart failure ICD-9 codes (the second visit was then assigned the heart failure date for the analysis).

Following application of inclusion and exclusion criteria, 1,210,145 patients were eligible for the study. Median age was 62 years, 5% were women, 19% were African-American, and median estimated glomerular filtration rate (eGFR) was 76 mL/min/1.73 m2. Patients who developed AKI were more likely to be older, be African-American, use either diuretics or renin angiotensin aldosterone system inhibitors prior to admission, have diabetes, have hypertension, and have sepsis during the index hospitalization.

Among 300,868 (80%) matched patients with and without AKI, groups were well matched by year of admission, demographics, preadmission comorbid conditions, and medication use, and characteristics of the index hospitalization. Of 150,434 patients with AKI, 83% had stage 1, 11% had stage 2, and 6% had stage 3.

Within a median follow-up of 1.7 years, 4.7% of the matched cohort had incident heart failure after the index hospitalization. The overall heart failure incidence rate was 27.8 per 1000 person years (95% confidence interval [CI], 19.3-39.9]. Patients who developed heart failure were more likely to be older, be white, and have proteinuria and lower eGFRs prior to the index hospitalization, diabetes and hypertension, and acute coronary syndrome during the index hospitalization. The incidence rate of heart failure was higher in patients with AKI compared with those without AKI: 30.8 (95% CI, 21.08-43.5) versus 24.9 (95% CI, 16.9-36.5) per 1000 person-years, respectively.

The cumulative incidence of heart failure was higher among patients with AKI. Following multivariable adjustment in the matched cohort, there was an association between a prior hospitalization for AKI and a 23% greater risk for incident heart failure within 2 years (hazard ratio [HR], 1.23; 95% CI, 1.19-1.27). To account for the matched nature of the data, the researchers repeated this analysis in sensitivity analyses, conducting a stratified cause-specific hazard model; the association of AKI and risk for incident heart failure was similar to that of the primary analysis (HR, 1.27; 95% CI, 1.23-1.32).

Compared with patients who had no AKI during the index hospitalization, risks for developing incident heart failure among patients with AKI stages 2 or 3 were similar to those of patients with AKI stage 1 (HR, 1.19; 95% CI, 1.12-1.28 and HR, 1.23; 95% CI, 1.19-1.28, respectively). Patients with AKI stage 2 or 3 had higher rates of death after discharge than patients with AKI stage 1 (incidence rate, 157.8 [95% CI, 136.5-181.7] per 1000 person-years vs 124.5 [95% CI, 105.4-146.4] per 1000 person-years, respectively).

Overall, the associations of AKI with risk for incident heart failure were consistent across subgroups by age, race, diabetes, coronary artery disease, and baseline eGFR category.

The researchers cited a few limitations to the study, including the matched study design that created the possibility that the matches differ from the overall population; the inability to perform adjudication of heart failure events of interest due to the use of validated ICD-9 codes to identify heart failure; and including only US veterans in the study, possibly limiting the generalizability of the findings.

The researchers said in conclusion, “In a large cohort of hospitalized US veterans, AKI was associated with the development of incident heart failure. These findings were consistent among important patient subgroups. These data contribute to the growing body of literature that has demonstrated that AKI is associated with significant long-term comorbidity. Future studies to identify underlying mechanisms and modifiable risk factors for heart failure in AKI survivors are needed.”

Takeaway Points

  1. There are few data on the relationship between acute kidney injury (AKI) and heart failure; researchers conducted a retrospective observational study to examine the association of AKI with incident heart failure.
  2. The study cohort included 300,868 hospitalized US veterans (2004-2011) with no history of heart failure.
  3. In multivariable models, there was an association between AKI and a 23% increased risk for incident heart failure (HR, 1.23; 95% CI, 1.19-1.27).