Acute and Chronic Cardiovascular Consequences of Acute Kidney Injury: A Systematic Review and Meta-Analysis

Abstract

Introduction: We examined whether patients with acute kidney injury (AKI) have a higher risk of developing atrial fibrillation (AF), heart failure (HF), acute coronary syndrome (ACS), and major adverse cardiac events (MACE) in the short and long term compared to patients without AKI, and if that risk is related to the severity of AKI. Furthermore, we investigated the influence of a cardiac event following AKI on the risk of all-cause mortality, length of stay in the intensive care unit and in the hospital.

Methods: We included English and Dutch retrospective and prospective cohort studies on adults (≥15 years) with AKI. Studies lacking epidemiological data, studies not using the consensus definitions (RIFLE, AKIN, KDIGO), animal studies, and studies on children were excluded. Studies were identified using the PubMed and Embase search engines. The last search was performed on the first of August 2021. For assessment of method quality, Newcastle-Ottawa Scale (NOS) for assessing risk of bias was used for cohort studies and heterogeneity was determined by the I2 statistic. Statistical analysis was performed using the Cochrane Review Manager (RevMan 5.3). The risk ratio (RR) and 95% confidence interval (CI) were calculated using the Mantel-Haenszel test. Results were presented in a summary caterpillar plot.

Results: We evaluated 14 studies comprising 736,210 patients. AKI was defined according to the RIFLE consensus in 1 article, to the AKIN criteria in 7, and to the KDIGO guidelines in 6. Of the 14 included studies, 4 were prospective and 10 were retrospective. In comparison with patients without AKI, we found that patients with AKI had a 94% increased risk of developing AF in the short term (RR: 1.94, 95% CI 1.35-2.79; p = 0.0004). In the long term, patients with AKI stage 1 had a 59% increased risk of developing HF and a 77% risk of developing ACS (RR: 1.59, 95% CI 1.07-2.34, p = 0.02 and RR: 1.77, 95% CI 1.68-1.88, p < 0.00001, respectively). Patients with AKI stage 2 had a 45% increased risk of ACS development (RR: 1.45, 95% CI 1.11-1.90, p = 0.006). AKI stage 3 was associated with a 164% increased risk of HF and a 95% increased risk of ACS development (RR: 2.64, 95% CI 1.71-4.08, p < 0.00001 and RR: 1.95, 95% CI 1.35-2.82, p = 0.0004, respectively). Analysis of studies not subdividing AKI into groups showed a 74% increased risk of HF, a 12% increased risk of ACS, and a 30% increased risk of developing MACE (RR: 1.74, 95% CI 1.51-2.01, p < 0.00001, RR: 1.12, 95% CI 1.07-1.17, p < 0.00001 and RR: 1.30, 95% CI 1.25-1.35, p < 0.00001, respectively).

Conclusions: Patients who developed AKI have an increased risk of developing AF at short-term follow-up and HF, ACS, and MACE beyond 30 days.

Keywords: Acute coronary syndrome; Acute kidney injury; Arrhythmia; Atrial fibrillation; Cardio-renal syndrome.