<b><i>Introduction:</i></b> The endothelial glycocalyx on the vascular luminal surface contributes to endothelial health and function. Damage to this layer is indicative of vascular injury, reflected by increased levels of its shed constituents in serum and an increase in the perfused boundary region (PBR) when measured in sublingual capillaries using the GlycoCheck™ device. We aimed to examine the longitudinal effects of kidney transplantation on the glycocalyx by measuring biochemical markers

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... of the glycocalyx and endothelial dysfunction and the PBR. <b><i>Methods:</i></b> We recruited healthy controls and stage 5 CKD patients scheduled to undergo a kidney transplant. Investigations were performed before transplant and then 1 and 3 months after transplantation. At each point, blood was collected for hyaluronan, syndecan-1, vascular cell adhesion molecule (VCAM-1), and von Willebrand factor (vWF), and a PBR measurement was performed. <b><i>Results:</i></b> Thirty healthy controls and 17 patients undergoing a kidney transplant were recruited (9 cadaveric and 8 live donation; 12 on dialysis and 5 pre-emptive). Before transplant, transplant recipients had greater evidence of glycocalyx damage than controls. After transplant, PBR improved from median 2.22 (range 1.29–2.73) to 1.98 (1.65–2.25) µm, <i>p</i> = 0.024, and syndecan-1 levels decreased from 98 (40–529) to 36 (20–328) ng/mL, <i>p</i> &#x3c; 0.001. Similarly, VCAM-1 fell from 1,479 (751–2,428) at baseline to 823 (516–1,674) ng/mL, <i>p</i> &#x3c; 0.001, and vWF reduced from 3,114 (1,549–5,197) to 2,007 (1,503–3,542) mIU/mL, <i>p</i> = 0.002. Serum levels of hyaluronan remained unchanged. <b><i>Conclusion:</i></b> The combination of reduced PBR and syndecan-1 following transplant suggests that transplantation may improve glycocalyx stability at 3 months after transplant.