Kidney Week

Abstract: PO2465

Endothelial Dysfunction in Dermal Biopsies of Patients with CKD Associates with Markers of Inflammation and Volume Overload

Session Information

• CKD: Inflammation, Endothelial Dysfunction, and Signaling
  November 04, 2021 | Location: On-Demand, Virtual Only
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2103 CKD (Non-Dialysis): Mechanisms

Authors

• Koch, Josephine, Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands

Josephine Koch,

• Hijmans, Ryanne S., Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands

Ryanne S. Hijmans,

• Ossa Builes, Manuela, Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands

Manuela Ossa Builes,

• Dam, Wendy, Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands

Wendy Dam,

• Pol, Robert, Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands

Robert Pol,

• Bakker, Stephan J.L., Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands

Stephan J.L. Bakker,

• Pas, Hendri H., Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands

Hendri H. Pas,

• Franssen, Casper F.M., Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands

Casper F.M. Franssen,

• van den Born, Jacob, Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands

Jacob van den Born,

Background

Cardiovascular (CV) morbidity is a major health problem in patients with chronic kidney disease (CKD). Besides traditional risk factors, CKD-induced endothelial dysfunction (ED) is involved in CV pathology. Of note, the luminal side of the vascular endothelium is covered by a protective endothelial glycocalyx (eGC) and indirect evidence indicates eGC loss and/or ED in CKD patients. So far, no direct endothelial profiling in non-renal tissue from renal patients has been performed. We aimed to investigate possible eGC loss and ED in CKD patients and its association with inflammation and volume overload.

Methods

During kidney transplantation, abdominal skin biopsies were taken from 11 kidney transplant recipients, of which 4 received hemodialysis. Abdominal skin biopsies from 9 healthy kidney donors served as control. Biopsies were stained for the eGC marker Ulex Eur I and the endothelial markers VEGFR2 and vWF. Subsequently, they were quantified and normalized in an immunofluorescence double staining for the pan-endothelial marker CD31. We also studied associations between the quantified endothelial markers and plasma markers of inflammation (CRP) and volume overload (NT-proBNP).

Results

Compared to healthy subjects, there was severe loss of eGC marker Ulex Eur I in renal patients (P=0.0008). Conversely, VEGFR2 was increased in renal patients, especially in those on dialysis (P=0.01). The same trend was seen for vWF, although this did not reach statistical significance. Skin water content was identical in all groups, which excluded dermal edema in patients with CKD. Compared with controls, plasma levels of CRP were increased in dialysis patients (P=0.02), whereas NT-proBNP was highly upregulated in all renal patients (P=0.03) which associated with VEGFR2 (R=0.29; P=0.03) and vWF (R=0.63; P<0.0001). Also, VEGFR2 and vWF were correlated (R=0.97; P<0.0001).

Conclusion

This study is the first to show direct evidence of dermal ED in patients with CKD. eGC damage has been shown by loss of Ulex Eur I and endothelial activation by increased VEGFR2 and vWF levels. In line with previous research, our results show ED to associate with inflammation and volume overload. More research is needed to further explore this pathophysiology.