Long term sequelae of acute kidney injury: A systematic review and meta-analysisof cohort studies using consensus definitions of exposure.

Introduction and Aims: Robust estimatesof the long-term outcomesof acute kidney injury are needed to inform clinical practice and guide optimal allocation of healthcare resources. This systematic review and meta-analysis aimed to quantify the association between acute kidney injury and chronic kidney disease, end stage kidney disease, and death, using consensus definitions of exposure. Method(s): Systematic searches were performed through EMBASE, MEDLINE, and grey literature sources to identify cohort studies reporting an association between acute kidney injury and at least one of the outcomes of interest. All studies in adults published after 2004, using standardised definitions for acute kidney injury (Risk, Injury, Failure, Loss, and End-stage kidney disease; Acute Kidney Injury Network; or Kidney Disease Improving Global Outcomes), which included a non-acute kidney injury control arm, and followed patients for at least 1 year were considered eligible. A modified Newcastle-Ottawa Scale was used to assess risk of bias, random effects meta-analysis was performed to estimate the pooled risk, and meta-regression was completed to identify potential sources of heterogeneity. Result(s): The search retrieved 3435 unique citations, of which 30 cohort studies (comprising 1,012,627 participants) were eligible for inclusion. The most frequent sources of bias related to inadequate follow up and variable adjustment for potential confounders. Compared to those without acute kidney injury, individuals with acute kidney injury were at significantly increased risk of chronic kidney disease (6 studies; 15,925 participants; hazard ratio [HR] 3.71, 95% CI 2.35-5.86; I2 93.1% p<0.001), end stage kidney disease (5 studies; 45,365 participants; HR 4.18, 95% CI 1.93-9.08; I2 88.8% p<0.001), and death (16 studies; 913,682 participants; HR 1.54, 95% CI 1.40-1.71; I2 85.6% p<0.001). The risk of death increased with greater acute kidney injury severity, and was highest in intensive care and