Uremic Toxins and Mortality in Patients With Acute Kidney Injury Prior to and During Continuous Kidney Replacement Therapy

Rationale & objective Uremia is an indication for continuous kidney replacement therapy (CKRT) in patients with acute kidney injury (AKI). Existing studies of uremic toxins in AKI have several limitations, including modest cohort sizes and small numbers of uremic toxins assessed per study. We aimed to better understand the uremic milieu and its association with mortality in critically ill patients with AKI before and during CKRT.Study design Single-center prospective observational study.Setting & participants We evaluated 21 uremic toxins in 89 critically ill adults with AKI enrolled before and during the first 3 days of CKRT and in 26 controls without kidney disease.Outcomes Thirty-day mortality.Analytical approach The primary outcome was 30-day mortality which was assessed using logistic regression modeling of each individual uremic toxin before CKRT and development of a uremic toxin (UT) score that accounted for (1) all 21 uremic toxins, (2) levels before and during the first 3 days of CKRT, and (3) directionality (ie, adjustment for levels that were either higher or lower in nonsurvivors).Results Thirty-day mortality was 52%. In AKI before CKRT, 15 uremic toxins were increased, and 6 were similar or lower in AKI as compared with controls and 20 of the 21 uremic toxins were not associated with mortality. Before and during the first 3 days of CKRT we observed that 4 uremic toxins were significantly lower in nonsurvivors. Accounting for this, our UT score could differentiate survivors and nonsurvivors.Limitations Single center and lack of a validation cohort.Conclusions Uremic toxins should not be assumed to be elevated in AKI, and elevated levels are not universally associated with mortality. These data are in line with the growing appreciation that therapies beyond kidney replacement therapy will be necessary to improve outcomes in AKI.