Indoxyl sulfate is associated with mortality after AKI - more evidence needed!

Patients who develop acute kidney injury (AKI) have significantly higher short-term outcomes including in-hospital mortality. The development of AKI has been associated with long-term consequences including progression to chronic kidney disease (CKD) and higher rates of cardiovascular disease (CVD) and mortality. In recent years there has been a growing push for the discovery of novel methods to diagnose AKI at earlier stages, and for an improvement in risk stratification and prognosis following AKI.Wang and colleagues assessed the association of total serum indoxyl sulfate (IS) levels, a protein bound uremic toxin, with 90-day mortality after hospital-acquired AKI (HA-AKI). These authors found that serum IS levels were significantly elevated in patients with HA-AKI (2.74 ± 0.75 μg/mL) compared to healthy subjects (1.73 ± 0.11 μg/ml, P < 0.001) and critically ill patients (2.46 ± 0.35 μg/ml, P = 0.016).The mechanisms of this relationship remain unclear, with a limited understanding of cause-specific mortality associated with either the high or low-IS group. One limitation of this current study is an understanding of the acceptable or expected higher level in IS during episodes of AKI. IS levels remained persistently elevated at day 7 compared to β2-microglobulin and serum creatinine which were both lower at 7 days. It is unclear, however, if levels of β2-microglobulin and serum creatinine were lower for other reasons, such as if any patients with AKI required dialysis.This work provides an important addition to the field of AKI research, specifically in the evaluation of readily measurable biomarkers and outcomes after AKI. Moving forward, further validation in studies of acute kidney injury are needed to develop a better understanding of IS levels at the time of AKI diagnosis and trends during the course of AKI.