Effects of perioperative fluid management on Glycocalyx injury in major urological oncology surgeries: a genetics and bioinformatics based approach

Background: The aim was to evaluate the effects of liberal and restrictive intraoperative fluid strategies on the gene-level markers of endothelial glycocalyx biology during major urological surgery. Specifically, NPPA (ANP) representing the ANP axis, the core proteoglycan SDC1 (syndecan-1), and key genes of glycosaminoglycan metabolism, HPSE (heparanase) and HAS2 (hyaluronan synthase-2), were examined. Methods: In a prospective, randomized design, peripheral blood samples were collected from 39 patients in the preoperative and postoperative periods. Total RNA was isolated, and MIQE-compliant RT-qPCR was performed. Primary endpoints were NPPA and SDC1 , while exploratory endpoints included HPSE and HAS2 . Analyses were performed using ΔCt-based calculations, and results were reported as 2−ΔΔCt fold-changes; statistical significance was set at two-tailed p < 0.05. Results: Preoperatively, SDC1 was suppressed in both groups. Postoperatively, the liberal group showed significant increases in NPPA ( p = 0.025) and SDC1 ( p = 0.0068), whereas in the restrictive group, SDC1 remained low ( p = 0.027) and NPPA showed a decreasing trend ( p = 0.064). No significant intertemporal changes were observed for HPSE and HAS2 ( p > 0.05). The observed transcriptomic pattern is biologically compatible with the hypothesis that liberal fluid loading may influence SDC1 dynamics through NPPA-related signaling; however, this interpretation remains hypothesis-generating because the primary randomized between-group comparison was not statistically significant. Conclusion: The association of the liberal approach with postoperative NPPA/SDC1 upregulation suggests a transcriptional-level stress/damage response affecting glycocalyx integrity. These findings suggest that genetic readouts (NPPA–SDC1 and exploratory HPSE/HAS2) may be useful for perioperative monitoring and generate hypotheses for further studies integrating multi-timepoint protein/ectodomain measurements. Trial Registration: This study registered at clinicaltrials. gov (NCT04780490).