BACKGROUND: Injury (shedding) of the endothelial glycocalyx layer, which alters local blood flow and microvascular permeability, is assessed by measuring components of this layer in circulating blood. The influence of renal function on their concentrations is unknown. METHODS: Plasma and urine concentrations of three shedding products (syndecan-1, hyaluronic acid, and heparan sulfate) and creatinine were measured over 5 hours in 15 healthy volunteers and 15 postoperative patients; this guaranteed a spread of kidney functions. Renal clearances were calculated. RESULTS: Low renal clearances of syndecan-1 (mean 3.5 mL/min) and hyaluronic acid (0.8 mL/min) correlated inversely with the 6-fold variability in the plasma concentrations of these substances (r = -0 . 45 and-0.49). Low creatinine clearance correlated inversely (r = -0.60) and plasma creatinine directly (r = 0.52) with the two-fold variability in heparan sulfate, which was the only shedding substance that also correlated with C-reactive protein (r= 0.51) and, therefore, showed higher concentrations after surgery. CONCLUSIONS: The present explorative study suggests that a 6-fold variability in the plasma concentrations of three commonly measured endothelial shedding products can be understood by the kidneys ability to excrete them. This finding has implications when interpreting results of studies where shedding is assessed.