Proteomic Signature of Urosepsis: From Discovery in a Rabbit Model to Validation in Humans

Urosepsis after upper urinary tract endoscopic lithotripsy (UUTEL) may cause uroseptic shock with high mortality, which can be prevented if early diagnosis and timely intervention are implemented with help of a diagnostic protein panel. The plasma of five rabbits of uroseptic shock and five controls was subjected to exploratory proteomics to search biomarker candidates from proteomic profiles related to uroseptic shock. Then, plasma from 21 nonsepsis and 20 urosepsis patients according to European diagnostic criteria of sepsis was enrolled in the validation study via targeted proteomics. Changes in a massive number of plasma proteins, mainly enriched in immune regulation, coagulation, structural repair, and transport activity, were observed in the rabbit model of septic shock. Fifteen proteins were identified as differential expression proteins between sepsis and nonsepsis patients. A diagnostic model composed of three proteins lipopolysaccharide-binding protein (LBP), clusterin (CLU), and vascular cell adhesion protein 1 (VCAM1) was developed for the early detection (2 hours postoperatively) of urosepsis after UUTEL, with a high area under the receiver operating characteristic (ROC) curve of 0.921. In conclusion, changes in the proteomic profile may reflect the underlying biological mechanisms during the development of urosepsis and produce diagnostic biomarkers for the early detection of urosepsis after UUTEL.