Elevated kynurenine levels and associated genetic polymorphisms result in increased extravascular hemolysis and lower hemoglobin increments in murine models of storage and PTR and in patients who receive transfusion in the clinics. Storage and PTR studies were performed in 350 mice with extreme diverse genetics (JAX Diversity Outbred mice). (A) Results show a significant (P < .001) negative association between kynurenine levels and posttransfusion recoveries in mice. (B) Leveraging a vein-to-vein database, we linked kynurenine levels and associated SNP for SLC7A5 to hemoglobin and bilirubin increments in 4470 single-unit transfusion events in patients requiring transfusion from products donated by REDS RBC Omics index donors. Results indicate significantly lower hemoglobin increments (B-C) and higher bilirubin levels (D) in patients receiving transfusion with donors carrying the SLC7A5 rs8052118 SNP in homozygosity. CI, confidence interval; GFP, green fluorescence protein; HoD, hen egg lysozyme-ovalbumin-Duffy; Ref, reference.