Relationship between acute kidney injury and mortality in poisoning – a systematic review and metanalysis

Abstract Rationale Three consensus classifications of acute kidney injury have been published. These are RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease published by the Acute Dialysis Quality Initiative workgroup), AKIN (published by the Acute Kidney Injury Network) and KDIGO (published by the Kidney Disease Improving Global Outcome workgroup). Acute kidney injury has been reported consistently as associated with worsened outcomes. However, toxicant-related acute kidney injury has been excluded from the studies used to validate the classifications of acute kidney injury. Objective To study whether poisoned patients who develop acute kidney injury, as defined by consensus definitions/classifications, have higher mortality compared to those who did not. Methods Databases were searched from 2004 to 2019 using the following keywords (KDIGO OR “Kidney Disease: Improving Global Outcomes” OR “Kidney Disease Improving Global Outcomes” OR AKIN OR “AKI network” OR “Acute kidney Injury Network” OR ADQI OR RIFLE OR “Acute dialysis quality initiative”) AND (intoxication OR poisoning OR overdose OR ingestion) AND (AKI OR kidney OR renal OR ARF). If data were available, we used a random-effects meta-analysis model and Fisher’s exact test to compare mortality in patients according to kidney function definitions (acute kidney injury vs not) and stages (stages vs no acute kidney injury), respectively. If data were available, we assessed the correlation between mortality and renal function (no acute kidney injury, risk/stage 1, injury/stage 2 and failure/stage 3) using the Spearman correlation. If available, we collected the results of statistical analyses in studies that have used acute kidney injury to predict mortality. Results Study selection. Thirty-three relevant studies were found, 22/33 retrospective studies (67%) and 11/33 prospective studies (33%). Paraquat was the most frequent toxicant involved (13/33, 39%). We found a disparity between studies regarding the timeframe during which mortality was assessed, the temporality of the renal function considered to predict mortality (initial/worst) and the criteria used to define/grade acute kidney injury across studies. Univariate association between acute kidney injury definitions/stages and mortality. Consensus definitions/staging of acute kidney injury were associated with higher mortality, using univariate analyses, in twenty-eight (RIFLE = 7; AKIN = 12; KDIGO = 9) studies included but not in five (AKIN = 4, KDIGO = 1). When available data were pooled, RIFLE (5 studies), AKIN (16 studies) and KDIGO definitions (8 studies) of acute kidney injury were associated with a higher mortality (Log unadjusted Odds ratios [95%-confidence interval], 2.60 [2.23; 2.97], 2.02 [1.48; 2,52] and 3.22 [2,65; 3.78], respectively). However, we found high heterogeneity (I2=54,7%) and publication bias among studies using AKIN. In ten studies with available data, the correlation between renal function (no acute kidney injury, risk/stage 1, injury/stage 2, failure/stage 3) and mortality was significant in 5 studies (RIFLE = 2; AKIN = 3), but not in five studies (RIFLE = 1; AKIN = 3; KDIGO = 1). Multivariate association between acute kidney injury definitions/stages and mortality . The definitions of acute kidney injury were associated with higher mortality in two studies (RIFLE = 2), but not in four studies (AKIN = 1 and KDIGO = 3. The stages of acute kidney injury (including one or more stages) were associated with higher mortality in four (RIFLE = 1, AKIN = 1 and KDIGO = 2). Conclusions All three consensus definitions/classifications were associated independently with increased mortality in poisoning but with disparity between studies reporting acute kidney injury.