Mortality and Cardiovascular Risk after AKI Requiring Dialysis

Among patients with end-stage renal disease (ESRD) requiring renal replacement therapy (RRT), there is a high burden of cardiovascular disease and early death; the risk is particularly high in the first year following initiation of dialysis therapy. Cardiovascular disease is a contributing factor in >50% of all deaths with known causes among patients with ESRD.

Results of recent studies suggest that there may also be an association between acute kidney injury (AKI) and increased risk of cardiovascular disease events. There is an association between AKI and increased inflammatory cytokines, a possible factor in increase of the risk of subsequent cardiovascular disease events via endothelial dysfunction or plaque rupture. Abrupt decline in kidney function in the 3 months preceding dialysis initiation is a strong, independent risk factor of early death after onset of ESRD.

AKI requiring dialysis (AKI-D) is commonly precipitant to ESRD and may be a factor in the high rates of early mortality and increased risk of cardiovascular disease in incident ESRD patients. There are few data on outcomes in this ESRD subpopulation.

Benjamin J. Lee, MD, and colleagues conducted a retrospective cohort study to test the hypothesis that after controlling for known vascular risk factors, patients with incident ESRD due to AKI-D are at higher short-term risk for death and cardiovascular disease compared with patients with ESRD not attributable to AKI-D. Results of the study were reported online in BMC Nephrology [doi.org/10.1186/s12882-018-0924-3].

The researchers utilized data from Kaiser Permanente Northern California (KPNC), a large, integrated healthcare delivery system providing inpatient and outpatient care for >4.1 million members in the San Francisco Bay area. All adult (≥18 years of age) KPNC members who developed AKI-D or who initiated chronic hemodialysis between January 2009 and September 2015 were identified. Eligible participants had ≥12 consecutive months of membership in the health plan as well as pharmacy benefits prior to RRT initiation. AKI-D was defined as receipt of RRT during hospitalization in the absence of any preadmission RRT (dialysis or transplant). Inpatient RRT included receipt of peritoneal dialysis, hemodialysis, or hemofiltration.

The two primary comparisons were (1) between patients with incident ESRD due to nonrecovery from AKI-D versus incident ESRD patients who did not have AKI-D and (2) between AKI-D patients who did recover kidney function versus those who did not recover adequate kidney function to discontinue dialysis. Recovery from AKI-D was defined as being alive and no longer requiring RRT for ≥4 weeks at 90 days following acute RRT initiation.

The researchers initially identified 13,213 hospitalized patients who received inpatient RRT and 6414 patients who initiated chronic hemodialysis as outpatients between January 2009 and September 2015. After applying inclusion and exclusion criteria, the final sample included 1865 patients with incident ESRD due to AKI-D, 3772 with incident ESRD not due to AKI-D, and 1347 AKI-D patients who recovered within 90 days following initiation of RRT.

Compared with the cohort with incident ESRD without AKI-D, those with AKI-D were older, more likely to be white, and had a higher burden of baseline cardiovascular disease. Compared with AKI-D patients who did not recover, those who did recover were younger, more likely to be white, had higher baseline estimated glomerular filtration rate (eGFR), and less likely to have pre-existing heart failure and other cardiovascular disease, hypertension, diabetes, or dyslipidemia.

Patients with incident ESRD due to AKI-D had higher all-cause death rates in unadjusted analyses compared with patients with incident ESRD who did not experience AKI-D. Crude rates of hospitalization for heart failure and acute coronary syndrome (ACS) were significantly higher in patients with incident ESRD due to AKI-D than in patients with ESRD without AKI-D; there were no significant difference in rates of stroke/transient ischemic attack (TIA).

In multivariable analyses, compared with patients with incident ESRD due to AKI-D, those with incident ESRD not due to AKI-D had a significantly lower adjusted rate of all-cause death (adjusted hazard ratio [aHR], 0.56; 95% confidence interval [CI], 0.47-0.67). Following further adjustment for potential confounders, there was also an association between ESRD not due to AKI-D and a lower adjusted rate of hospitalization for heart failure (aHR, 0.45; 95% CI, 0.30-0.70). There was no association between ESRD not due to AKI-D and lower adjusted rate of ACS or stroke/TIA.

In sensitivity analyses that excluded AKI-D patients with pre-existing eGFR ≤24 mL/min/1.73 m2, crude and adjusted results for death and hospitalization for heart failure were similar (aHR, 0.43; 95% CI, 0.28-0.67 and aHR, 0.61; 95% C I, 0.27-1.37, respectively).

Crude rates of all-cause death, ACS, and stroke/TIA were lower in patients who recovered from AKI-D compared with those who did not recover. In multivariable analyses, there was an independent association between recovery from AKI-D and lower mortality (aHR, 0.70; 95% CI, 0.55-0.88) compared with non-recovery. There were no significant adjusted differences in rates of heart failure, ACS, or stroke/TIA. In sensitivity analyses, both crude and adjusted results were similar (aHR for death, 0.59; 95% CI, 0.44-0.80).

The researchers did cite some limitations to the study, including possible misclassification of patients with AKI-D who initiated dialysis due to progression of advanced CKD rather than true AKI, lack of details on inpatient dialysis prescriptions (modality, dose, or use of anticoagulation) or etiology of AKI-D, and limiting the study population to insured patients from Northern California.

“We found that patients who transition to ESRD via AKI-D are at higher risk for short-term death and heart failure hospitalization compared with those who start chronic dialysis without experiencing AKI-D. Our findings indicate that the high short-term mortality in incident ESRD patients may be explained, at least in part, by the subset of patients who developed ESRD via AKI-D. Furthermore, our findings suggest that this subset of incident ESRD patients may have worse outcomes because of pre-existing heart failure. Recovery from AKI-D was also independently associated with lower short-term mortality. Collectively, these findings suggest that aggressive surveillance for and medical management of heart failure in ESRD patients may be a potential strategy for reducing early mortality after AKI-D. Further studies are warranted to evaluate whether promotion of renal recovery from AKI-D and systematic surveillance and intervention for heart failure can improve outcomes in this vulnerable patient population,” the researchers said.

Takeaway Points

  1. Researchers conducted a retrospective cohort study to test the hypothesis that patients with acute kidney injury requiring dialysis (AKI-D) who recover adequate kidney function would have improved outcomes compared with patients who develop incident end-stage renal disease (ESRD).
  2. Among patients with AKI-D, those without incident ESRD had lower adjusted rates of all-cause death compared with patients with incident ESRD.
  3. There was also an association between ESRD not due to AKI-D and lower adjusted rates of all-cause death, and hospitalization for heart failure, but not acute coronary syndrome or stroke/transient ischemic attack.