Blood and Urine Transcriptomes Reveal Complementary Host Responses and a Creatinine-Associated Urinary Transcriptional Axis in Sepsis

Background/Objectives: Sepsis is characterized by systemic immune dysregulation and organ dysfunction, but transcriptomic profiles from different biofluids may provide partially overlapping and distinct molecular readouts of the host response. We characterized transcriptomic profiles of whole blood and urinary cellular fractions in sepsis, with particular emphasis on a urinary transcriptional gradient associated with continuous serum creatinine and on whether this association was mirrored in matched blood.

Methods

Targeted RNA sequencing was performed on whole blood from 35 patients with sepsis and 10 healthy controls and on urinary cellular fractions from 21 patients with sepsis and 7 controls using the Ion AmpliSeq Transcriptome Human Gene Expression workflow. Differential expression was assessed with DESeq2, with sequencing-adjusted sensitivity models where appropriate. Sensitivity analyses addressed the highest creatinine value, sex and age, and matched blood–urine creatinine-associated effects.