Plasma concentrations of syndecan-1 are dependent on kidney function.

Robert G Hahn,Joachim Zdolsek,Markus Zdolsek

doi:10.1111/aas.13801

Robert G Hahn, Joachim Zdolsek + Show 1 more

Open Access

https://doi.org/10.1111/aas.13801

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Abstract

Elevated plasma concentrations of syndecan-1 and heparan sulfate in studies of trauma, sepsis, and major surgery are commonly assumed to indicate acute glycocalyx degradation. We explored a possible role of the kidneys for these elevations. Plasma and urine concentrations of syndecan-1, heparan sulfate, and biomarkers of inflammation were measured over 5hours in 15 hospital patients treated for post-burn injury. The renal clearances of syndecan-1 and heparan sulfate (CLR ) were calculated and their influence on the plasma concentration predicted by simulation. The urine/plasma concentration ratio was 0.9 (0.3-3.0) for syndecan-1 and 2.8 (2.0-4.3) for heparan sulfate. The CLR varied 250-fold for syndecan-1 and 10-fold for heparan sulfate. Multiple linear regression analysis showed that CLR for syndecan-1 was positively associated with the creatinine clearance (P<.0032) and the urine flow (P<.015). CLR for heparan sulfate increased with interleukin-6 (P<.003) and the urine flow (P<.01). Simulations suggested that a change in CLR from the mean of the highest 3 to the lowest three values would double plasma syndecan-1 within 4hours and cause a 7-fold rise after 24hours. A similar change in CLR for heparan sulfate would triple the plasma level within 24hours, even if no increased shedding of the glycocalyx takes place. The renal elimination of syndecan-1 and heparan sulfate varied greatly. A change in kidney function, which is common after trauma and major surgery, might alone induce several-fold changes in their plasma concentrations.

Highlights

Measuring syndecan-1 and heparan sulfate concentrations in plasma is a common way of assessing the integrity of the endothelial glycocalyx layer
This present study is a secondary report of a prospective single- center open-label trial of the volume effects and capillary leakage of 20% albumin in 15 patients recruited from the Burns Unit of Linköping University Hospital, Sweden, between October 2016 and January 2019.6,7 The study was approved by the Regional Ethics Committee of Linköping (Dnr 2016/333-32) and the Swedish Medical Products Agency (Eu-nr 2016-000996-26) and was registered at clinicaltrials.gov (NCT02952378)
The renal clearance (CLR) of syndecan-1, heparan sulfate, and creatinine during the 5 hours experiment was calculated as the product of their urinary concentration and the excreted urine volume divided by the average plasma concentration at 0 and 300 minutes

Summary

| INTRODUCTION

Measuring syndecan-1 and heparan sulfate concentrations in plasma is a common way of assessing the integrity of the endothelial glycocalyx layer. More than 200 studies have been published that show the frequent occurrence of threefold to fourfold elevations of the plasma concentrations of endothelial surface proteins in acute and chronic inflammation, trauma, sepsis, and major surgery.1-3 A major challenge is to find different ways to avoid these elevations, as they are interpreted to imply acute injury to the glycocalyx layer.[4] the metabolism of these glycocalyx components is poorly understood, and events other than glycocalyx degradation might possibly explain a rise in their plasma concentrations Their production could be upregulated or their elimination could become less efficient.[4,5]. The CLR of syndecan-1 and heparan sulfate were calculated (primary outcome), their variability was examined, and simulations were performed to predict how the plasma concentrations are likely to change when CLR is varied (secondary outcomes)

| METHODS

| DISCUSSION

Findings

| CONCLUSIONS