Serum metabolite profiles predict outcomes in critically ill patients receiving renal replacement therapy.

ABSTRACT

Acute kidney injury (AKI) requiring renal replacement therapy (RRT) is associated with increased incidence of dialysis dependence and portends high mortality in critically ill patients. At the early stage of RRT, serum metabolic biomarkers might differntiate patients with a high risk of mortality or permanent kidney injury from those who can recover. Serum samples from participants enrolled in the Veteran's Affairs/National Institutes of Health Acute Renal Failure Trial Network study were collected on day 1 (n = 97) and day 8 (n = 105) of randomized RRT. The samples were further evaluated using LC/MS-based metabolic profiling. A model predicting mortality by day 8 was built from samples collected on day 1 and based on four metabolites with an area under the curve (AUC) of 0.641. A model most predictive of mortality by day 28 was built from the levels of 11 serum metabolites from day 8 with an AUC of 0.789. Both day 1 and day 8 samples had lower serum levels of 1-arachidonoyl-lysoPC and 1-eicosatetraenoyl-lysoPC (involved in anti-inflammatory processes) in the critically ill patients who died by day 8 or day 28. Higher levels of amino acids and amino acid metabolites in the day 8 model predicting < day 28 mortality may be indicative of muscle wasting. A kidney recovery biomarker panel based on the serum levels of three metabolites from day 8 samples with an AUC of 0.70 was devised. Serum metabolic profiling of AKI critically ill patients requiring RRT revealed predictive models of mortality based on observed differences in four serum metabolites at day 1 and 11 metabolites at day 8 which were predictive of mortality. Significant changes in the levels of these metabolites suggest links to inflammatory processes and/or muscle wasting.