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Uremic Toxins and Mortality in Patients With Acute Kidney Injury Prior to and During Continuous Kidney Replacement Therapy
Journal article   Open access   Peer reviewed

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

Isadore M. Budnick, Samel Park, Kristy Rolloff, John T. Brinton, Julie A. Reisz, Daniel Stephenson, Sarah M. Haeger, Amanda Smith, Kayo Okamura, Zhibin He, …
Kidney medicine, Vol.8(9), 101449
09/2026
DOI: 10.1016/j.xkme.2026.101449
PMCID: PMC13475231
PMID: 42602590
url
https://doi.org/10.1016/j.xkme.2026.101449View
Published (Version of record) Open Access

Abstract

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. Single-center prospective observational study 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. Thirty-day mortality. 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). 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. Single center and lack of a validation cohort. 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. Uremic toxins are harmful plasma solutes that accumulate in kidney failure and cause harm. We measured 21 plasma uremic toxins in critically ill patients with AKI for 4 days: just before and during 3 days of continuous kidney replacement therapy (CKRT). Before CKRT, not all uremic toxins were elevated compared with patients without kidney failure. During CKRT, 4 uremic toxins were lower in patients that died at 30 days. We developed a uremic toxin score to predict mortality at 30 days that accounted for (1) all 21 uremic toxin levels, (2) all 4 days, and (3) directionality (whether increased or decreased in survivors versus nonsurvivors). The UT score was able to distinguish 30-day survivors from nonsurvivors on all days.
 Acute kidney injury composite Z score continuous intensive care unit kidney replacement therapy uremic milieu uremic toxins

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