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Endothelial dysfunction and low-grade inflammation in the transition to renal replacement therapy


Autoři: April C. E. van Gennip aff001;  Natascha J. H. Broers aff001;  Karlien J. ter Meulen aff001;  Bernard Canaud aff003;  Maarten H. L. Christiaans aff001;  Tom Cornelis aff005;  Mariëlle A. C. J. Gelens aff001;  Marc M. H. Hermans aff006;  Constantijn J. A. M. Konings aff007;  Jeroen B. van der Net aff001;  Frank M. van der Sande aff001;  Casper G. Schalkwijk aff008;  Frank Stifft aff010;  Joris J. J. M. Wirtz aff011;  Jeroen P. Kooman aff001;  Remy J. H. Martens aff001
Působiště autorů: Department of Internal Medicine, Division of Nephrology, Maastricht University Medical Center+, Maastricht, the Netherlands aff001;  NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands aff002;  Medical Office EMEA, Fresenius Medical Care Deutschland GmbH, Bad Homburg, Germany aff003;  Montpellier University, Montpellier, France aff004;  Department of Nephrology, Jessa Hospital, Hasselt, Belgium aff005;  Department of Internal Medicine, Division of Nephrology, Viecuri Medical Center, Venlo, the Netherlands aff006;  Department of Internal Medicine, Division of Nephrology, Catharina Hospital Eindhoven, Eindhoven aff007;  Department of Internal Medicine, Maastricht University Medical Center+, Maastricht, the Netherlands aff008;  CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands aff009;  Department of Internal Medicine, Division of Nephrology, Zuyderland Medical Center, Sittard-Geleen, the Netherlands aff010;  Department of Internal Medicine, Division of Nephrology, St. Laurentius Hospital, Roermond, the Netherlands aff011
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0222547

Souhrn

Introduction

End-stage renal disease (ESRD) strongly associates with cardiovascular disease (CVD) risk. This risk is not completely mitigated by renal replacement therapy. Endothelial dysfunction (ED) and low-grade inflammation (LGI) may contribute to the increased CVD risk. However, data on serum biomarkers of ED and LGI during the transition to renal replacement therapy (dialysis and kidney transplantation) are scarce.

Methods

We compared serum biomarkers of ED and LGI between 36 controls, 43 participants with chronic kidney disease (CKD) stage 5 non-dialysis (CKD5-ND), 20 participants with CKD stage 5 hemodialysis (CKD5-HD) and 14 participants with CKD stage 5 peritoneal dialysis (CKD5-PD). Further, in 34 and 15 participants repeated measurements were available during the first six months following dialysis initiation and kidney transplantation, respectively. Serum biomarkers of ED (sVCAM-1, E-selectin, P-selectin, thrombomodulin, sICAM-1, sICAM-3) and LGI (hs-CRP, SAA, IL-6, IL-8, TNF-α) were measured with a single- or multiplex array detection system based on electro-chemiluminescence technology.

Results

In linear regression analyses adjusted for potential confounders, participants with ESRD had higher levels of most serum biomarkers of ED and LGI than controls. In addition, in CKD5-HD levels of serum biomarkers of ED and LGI were largely similar to those in CKD5-ND. In contrast, in CKD5-PD levels of biomarkers of ED were higher than in CKD5-ND and CKD5-HD. Similarly, in linear mixed model analyses sVCAM-1, thrombomodulin, sICAM-1 and sICAM-3 increased after PD initiation. In contrast, incident HD patients showed an increase in sVCAM-1, P-selectin and TNF-α, but a decline of hs-CRP, SAA and IL-6. Further, following kidney transplantation sVCAM-1, thrombomodulin, sICAM-3 and TNF-α were lower at three months post-transplantation and remained stable in the three months thereafter.

Conclusions

Levels of serum biomarkers of ED and LGI were higher in ESRD as compared with controls. In addition, PD initiation and, less convincingly, HD initiation may increase levels of selected serum biomarkers of ED and LGI on top of uremia per se. In contrast to dialysis, several serum biomarkers of ED and LGI markedly declined following kidney transplantation.

Klíčová slova:

Biology and life sciences – Biochemistry – Biomarkers – Physiology – Interleukins – Developmental biology – Molecular development – Adhesion molecules – Medicine and health sciences – Nephrology – Medical dialysis – Chronic kidney disease – Surgical and invasive medical procedures – Transplantation – Organ transplantation – Renal transplantation – Urinary system procedures – Immune physiology – Immunology – Immune system – Innate immune system – Cytokines – Immune response – Inflammation – Diagnostic medicine – Signs and symptoms – Pathology and laboratory medicine


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