A Study of the Correlation Between Donor UDP-Glc and Transplanted Kidney Function

Overview

Kidney transplantation is the preferred treatment for end-stage renal disease (ESRD), however, organ shortage is the primary bottleneck restricting the progression of organ transplantation.1 Organs from Expanded Criteria Donors (ECD) have the potential to greatly increase the donor organ pool. However, they also require careful selection and utilization. Deceased kidney donors often had a history of central nervous system fluid regulation disorders and inflammation mediator release, which led to hemodynamic instability, electrolyte and acid-base imbalances, and with a higher risk of primary graft non-function (PNF) or delayed graft function (DGF) post-transplantation.2,3 Searching for appropriate and effective biomarkers to assess renal quality and predict DGF is a hot topic in the field of kidney transplantation. Uridine diphosphate-glucose (UDP-Glc) is a damage-associated molecular pattern molecule (DAMPs) released by damaged cells.4 UDP-Glc is synthesized in the cytoplasm, then transported into the lumen of the endoplasmic reticulum and Golgi apparatus, where it regulates the synthesis of carbohydrates and acts as a substrate to facilitate glycosylation reactions.5 And UDP-Glc is an endogenous excitant of the G protein-coupled P2Y14 receptor.6 Additionally, the human P2Y14 receptor is expressed at high levels in adipose tissue, stomach, intestines, specific regions of the brain, skeletal muscle, spleen, lungs, and heart.7 UDP-Glc released plays a significant role in extracellular signaling within these tissues.8 Activation of P2Y14 promotes neutrophil infiltration, the recruitment of monocytes and macrophages, and the activation of the immune response, ultimately leading to tissue damage.9 Research has discovered that intercalated cells (ICs) in the collecting duct of the kidney act as sensors for UDP-Glc, and when the P2Y14 receptor on their apical membrane is activated, ICs produce chemotactic cytokines that attract neutrophils to the kidney, causing kidney inflammation and the onset of acute kidney injury (AKI).10,11 Furthermore, studies have shown that the concentration of UDP-Glc in the urine of AKI patients is higher compared to patients without AKI.12 UDP-Glc hydrolyzes slowly in the extracellular environment, which results in UDP-Glc being highly stable and easily detectable.5,13 In conclusion, donor urinary UDP-Glc can be serve as an appropriate and effective biomarkers to assess renal quality and predict DGF. The study aimed to investigated the correlation between donor urinary UDP-Glc levels and graft function post-transplant in recipients. We hypothesized that the higher the donor urinary UDP-Glc levels, the more severe the kidney damage, resulting in a higher probability of DGF. It will provide transplant surgeons with a novel strategy to predict DGF earlier and more accurately without invasive procedures, while also reducing medical costs.